CA2558704A1 - Use of paliperidone for the treatment of sleep disturbances and/or excessive daytime sleepiness in psychiatric patients - Google Patents
Use of paliperidone for the treatment of sleep disturbances and/or excessive daytime sleepiness in psychiatric patients Download PDFInfo
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Abstract
The present invention provides a pharmaceutical composition, and provides for the use thereof for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient is need thereof. The pharmaceutical composition comprises a therapeutically effective amount of paliperidone, its pharmaceutically acceptable acid addition salts, enantiomeric forms, or esters thereof, together with a pharmaceutical carrier, and provides a relatively low plasma, concentration variation of paliperidone to the psychiatric patient in need of treatment. The present invention also provides for the use of a pharmaceutical composition as defined above for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness.
Description
TJSE OTr' pALIPERIDONE FOR'T'H TI~EATM '~' OF SLEEP IaISTURBANCES
AND/O~ JiL'"XCFSSIVE IJA~E L,E,~~'PINIfr ~hT PSYCfI~ATRIC PAT '~.~.'NTS
~ III
This Invention relates to the ty~of p~liperid ' for the treatment of persistent sleep disturbances andlor excessive ~ ime'~ sleepin , in psychiatric patients.
Patients with mental illness ci~ ~ halve sleep °y.urbances including insomnia, and I
excessive sleeping. Sleep disturbances are common patients with schizophrenia, depression and bipolar disorders. rorie am~le, patie ' with schizophrenia appear to have lvnge~t sleep latency, a higher xty ber ~ f arou dwing sleep and increased periods of wakefulness after sle asset cons ~ ed Pith than ~1 non s chiatric control an s.
eP ?~ p y ~ p (Tondos et al. and Miller at al.). 1'ati~ .tS b+~ing trea ~ Far psychotic symptoms utay also suffer ~rom excessive daytime sleepp~e~s orl drows' v associated with both sleep disturbance and sedation caused by ant psy'hotic m Iyations. Additionally, the excessive sedation caused by souse ari syr~totic m I ations can result in impaired cogtitive functions and other sympto~7r ~th~t interfe. Nith successful treatment of the patient. More importantly, sedation c impair a pa , t's quality of life and efforts to lead a normal life. . I . .
r We have discovered that, by ' ting psychi.t ~: patients who suf~'er .from excessive daytime sleepiness and/or ~ eepl~ disturb ~ with a pharmaceutically effective amount of paliperidone, its pharmaceu ically accept ~u acid addition salts, enantiomeric forms, and esters, delivered at a relativ l.y clPnstant 1 ' ma level, these patients will have significantly reduced daytime drawai~ ss a~dJor sle ' disturbances.
W one emboclirnent, the presep iity,~lntion pr ales for the use of a pharmacoutical composition comprising a therapet~oa~ly e:~fective ~ uut of paliperidone, its pharmaceutically acceptable acid a~d~it on salts, ena ~lmerie forms, or esters thereof, together with a pharmaceutically acc~p~tahlg carrier, the treatment of excessive DOCSTOR 117613$11 daytime sleepiness and/ori ~ance luatric patient iri rie~l a sleep dis in a~ thereof, the ps pharmaceutical composition; .relativelyplasma concentratiaxl providir~ ' 1 variation of paliperidane to the "need ~eut.
psychiatric patien of tre )'n yet another embodiment, resent n provides ;for the rise tl rove of a pharraaeetttical compositionr a therapetttiIly effective amotmt of, compris paliperidorie, its pharmaceutically~ 'table Lion salts, enantiomeria tic ' acid forms, or a esters thereof, togetherc pticallyable carrier, in the preparation with a pharm acts of a medicament for the treatment, v,~ daytime.~piness andlor a sleep of exc . distttrbaace in a psychiatric patient p.e pharmacgoal composition providing in need there a relatively low plasma : anon ~idane to the psychiatric concentration ' of pali patient in need of treatment.
rn another embodiment, ration a pharmaceutical composition the it provid ' comprising a therapeutically attnt ~ridone, its pharmaceutically effectiv of p acceptable acid addition, eric ~sters thereof, together salts, enanti 1 :forms, with a o pharmaceutically acceptableI the tieatiari.f excessive daytime sleepiness carrier, f and/or a sleep dishirbancet 'c patient~ed thereof, the pharmaceutical in a psycia in composition providing p lasma ration variation of paliperidone a relatively 1 cc~na to the psychiatric patienti nt.
in need oftreai a In another emboditnent, tion for the use of a pharmaceutical the j pravid composition comprising a therapeuta ~ r y effectiveotuit of paliperidone, ~ its l .
pharniaceuti.cally acceptfible~ n salts,omeric Forms, or esters acid ad i en thereof, together with a pharmaceutically' ble carrier,r improving sy111ptoms of schizophreiua in a psychiatric. rieed wherein the symptoms are patierl v'..thereo selected from the group consisting bauces ~:assive daytime sleepiness, of sleep da anti the .
pharmacrrutical composition~ relativelyplasma concentration variation pT4V.ld1 " 1 o.f paliperidona to the ' .need lent.
psychiatric pati 1. l of'tr l In another embodiment, Lion for the 'use of a pharmaceutical the :i n 1 provid composition comprising . y affectiveaunt of palaperidone, a therapeuti " ~ iks pharmaceutically acceptablep rt salts,omeric forms, ar esters acid ad i en lhereo~
together with. a pharmaceutically able the manufact'eue of a ace ~ carrier,medieatment fox irnprovirig symptoms is in kris patient in need thereof, of schizop r a psych PUC.STOCt 11?613S1i I li~i i. il wherein the symptoms o ~ the sisting ofsleep disturbances are selected group and excessive daytime sleepiness, ~ceuticalosition providing a the p cc relatively low plasma concentration - ~ridonc sychiatric patient variation of p to tl in need of treatment.
In still another embodiment,~ ;invention'des a pharmaceutical 1, composition comprising a therapeuticallyy cant eridone, its pharmaceutically effecti of p:
acceptable acid addition~ uric stets thereof, together salts, en.ant farms, wi.tta a pharmaceutically acceptable~ ~ impmvingptoms of schizopbrenia carrier ' in a psychiatric patient h ~oit~. ~s are selected frorn in need thereof, the the group syn consisCing of sleep ~ ~4ssivo sleepiness, the pharmaceutical disturbances and days composition providing ~lasrr~ tration variation of a relatively 1 con paliperidone to the psychiatric patient~ e~nt.
in need of tre Tliese and other obj ~dantages resent invention rt'1ay ects and of c be appreciated from a ~ applicatim review of the p I
Figure 1 provides a graphie~.~ lu~esentation c~~~ relatively constant plasma release pm.ftle of, paliperidone from 1drelease e'form such as an OROS dosage a contr do form as compared to an immediate1~se form iperidone. The data paints shown ~ of , for day 1 are measured at specific~-intervalsescribed in Example 4. p'or days ti as 2 through 6, data points were me ~t 2 and s.post administration and constitute 2~ h an average of the results from ~,p at ' The data points for paliperidone each each , ti shown between days 6 and 7 shoalaiple times during tha day, illustrating ~ tp~ . the intraday variance in plasma level , tration~peridone.
c ~ of ~
Sleep dishtrbances axed exec Isi !~ daytime il siness occur in patients suffering from many mental illnesses. These I~u ~jects spend excessive amount of time in a sleep UOCS"COR: 117b 13811 I >I' I 6 state or unable to maintain~ ~ pie efixlness during a period of the day a satisfa o;. ~ ee of when wakefi>_lness is required~ I
or de I
As used herein the Term Iap!at>q baqce'ha7.1 mean a condition in which ate "sl ' individual has longer sleep I f ~usals during sleep, anal latency, i ;her number~
increased periods of wakefulnessIr.~r~ ep onset. ~ypersomnia, dyssomnia and a ~ ~ t~
parasomnias). These disorders~ ~ iiagnosedg conventional methods such as ma b a are commonly employed in uto, iy ~somnography).
a sleep (e.g.
t As used herein the term a ~ ve ~ 1epiness" (EDS) shall be used "E ' aytim ; I
interchangeably with the 1 ' oaf c f" and shall mean a cotldition in term '~a . spnzno t which an individual feels i ~. ariyg d finds it di.;fficGVlt to resist the very dro y the d~~ i 'loge to fall asleep, whether 1 ivir~ualtxen enough nighttime sleep.
or not ha;
' Bxcessi.ve da me slc inESSi ' ~:.flztled TD I as s:l jness occurring in a situation yti ep ( ;
when an individual would ~ be awaked alert. Clinically the symptoms of be expec :
EDS can be quantified and ~ i, ~ vafietyys, including but not limited toy measur i of I I
~ ' the Multiple Sleep Latency l.[' (S in MA and Dement WC, Sleep Test ~e Cars ~
19$2;5 Suppl 2:567-72) , ~ ce ~f mess Tast (MWT) (See, Mitler the M ' I~Walct-I
-MM, et al. Elecirr~encephalogrp I i Cli rola~ysiWl,2;3(6);65$-61) or the StauGord I
Sleepiness Scale (SSS) (See,~ ;t a~ )tysiology, 1973;10{4):431-b) (gee Todd ~I, Fs~re)n also, Arand D et al. Sleep,) 3-1' ). causes of EDS are multiple and the 2005;28 . T7 ~
,, use ofthe term EDS hereina d i ~ ypartipular cause or etiology.
is not i ~ Idly ' People with E'DS frequentlyp a fa 1. situations where they need or ' doze,. ' asleet ~
want to be fully awake and a ~ ~Igri made wlien the symptoms of FrDS
alert. ~ sis can interfere signi~.cantly ~ Lity t>rate and perform daily tasks and with a pers I to cpnn routi-nes such as work, ' I iti~ a, car or operating othor hazardous family reap , drivi~ -machinery or general. quality of lif I
The term "psychiatric patiot'. d hereiefers to a human, who has .been the ~
object of trcatnxent, or a ~ lleia~aIr!', and tha term "mental disorder"
cxpcrinxent fq , di!sor ( , ~ Cer~ rll'orrided in the Diagnostic and a~Iso encompasses mental to tho:, illnesses I
Stafiistical Matlual (DSM ~nc P~yclogical Association (APA). These III or N) I
mental disorders include a ~ pal ~ other disease states in which sclxizophr . di$oa ' psychosis, aggressive behavior,ty~ de~ ~videneed. Schizophrenia refers to arlxi ' 1 ~pressio~~
17UC5'CC~R: 117413811 conditions characterized schiza(fec~ e~disorder anal schizophreniform as schizoph>n disorders, in DSM-IV-TR ~ I3 ~ oll Disorder refers such as cal: 295. to a conditions characterized as a n SM-I-TR , ch as category 296.xx Bipolar Disorder,' ~ including ~
I3.ipolar 1 and Bipolara ~SM--l~ prepared by the Taslc Disorder II. Force on Nomenclature and StatisticsI Ficanyclii'c Association, and of the ~ . P provides clear j descriptions of diagnostic ~tholo'c , ological conditions, categorie ~ ps which are psychoses or may be ~choticfeats include, but are associated wi not limited to the following disorders , icteriin ~ DSM~1V-TR. Diagnostic that have been. c ' t and Statistical Manual r,'Revise, d. { 1994). The numbers of Mental Disord ~ i 3r in parenthesis refer to c~Glrgorie'~'her ')led artisan will the DSM-N-T recognize that there are alteniative , ~logiesand ~ siFcation systems nomenclatures, c for pathologic psychological conditionss ystemevo.~ wi.th .medical scientific and that th ~ progress.
Examples of pathologicisgiaalondins which may be treated ps ! ~ include, but are not limited ~ datio{31 Moderate Mental Retardation to,. Mild Mental (318.0), Severe Mental~ ~.1),fo Mental Retardation Retardation ;> (318.2), Mental Retardation fi(319Acs ~ is Disorders (299,00), Severity Unspe a ~ v Rett's Disorder (299.$0), ~ tivesord~ 299.10), Asperger's Childhood Disin D Disorder ~~ ( (299.80), Pervasive i ordert ~ rwise Specified.{299.$0), Developmental ~ O
Attention-Deficit/Hyperaciivityr<!'r in.eda (31.4.01), Attention-Dis~l Cam DeficitlHyperactivity n jlately~~ttev 've Type (314.00), Disorder Pred' i Attention-De~eit/Hyperactivity ~Il~atclyIype: tjve-Impulsive Type Disorder Pred' (314.01), ~
Attention-Defieit/Hyperaetivity 'r (314.Conduct Disorder ( Dis NOS Childhood-i Onset and Adolescent ! psitionhe ~ t Disorder (313.81), Type 312.8) Disntptive Behavior Disorder Not e ~ 2! . olitary Aggressive Otherwise S; p iIf 9), Type (312.00), ed (3 Conduct Disorder, Undifferentiated ~e 90),urette's Disorder (307.23), I (312 Chronic Motor Dr Vocal Tis 2 ~'ra~nsit jsorder (307.21), Tic Disorder (307. Ti Disorder NOS (307.20), Alcohol ~ ~irium291.Alcohol Withdrawal Intoxicati Delirimx'L
(291.0), Alcohol-InducedD ~entia291.' , Alcohol-Lnduced Persisting ~ Psychotic Disorder with Delusions (291.5), A1 ~ t;~1-Indu ed ; chotic Disorder rwith Hallucinations (291.3), Amphetanui ~~s a~ Sxmil ly ity Sympathomimetic Into~cicatior~
(292.89), Amphetamine or Sinularl~~ I,ling S pa. ~ mLimetic Delirium (292.81), DOCSTOR: 1 L7ti1.38\I
Amphetaznine or Similarly'"athomi~etiinduced Psychotic with Acting ~' ~~~iag Delusional (292.11), Amphetamine dSympa unimeti.c Induced Psychotic or Similarl ~ r'I ed with Hahucinations (292.12),'uPsychati Disorder with Deh~sians Cannabis~I dith HalIucin(292.11),-.
Car~na>5is-Induced ~;~ (292.81),fans (292.12), Cocaine Psychotic Disor ~C Intoxication (292.89), Cocaine Intoxication'red Psychoti;sine-reduced Psychotic De ' r~~:$9), Disorder with Delusions (292.11), rIal~uci disorder with Hallucinations Cocaine- ~~ 'c ogee Intoxication Delirium (292.12), Halluciogen disorder th belusions (292,11), Intoxication ~ gas (292.12), Hallucinogen-.induced (292.81), Hallucinogen-Induced .~ with Pa ; Delu hallucinogen-Induced Psychotic di Mood. Disorder (292.84),ez;Ilnduced~ty Disorder (292.89), )"rallucino ~
Hallucinogen-Related erwi.se eci (292.9), Inhalant Disorder Note' Spec Intoxication (292,89}, Inhalant 'u~ (292,$1;x,slant-Induced Persisting Intoxication Deli ' Dementia (292.82}, Inhalant-Lnduced ;sorder elusions {292.11), Psychat' with Inhalant-Induced Psychotic with Hallucinations2,I I:nhalantTIneed Mood Disorder (292.89), (292.~~
TTrHalant-Induced Anxiety2~.89), .Related Disoxder Not Disorder ~ Inh.al.a Otherwise Specified (292.9), ni~lelirium$1), Opioid-Induced Opioid Intoxieati (29 Psychotic ~
Disorder with Deh>sionsi~I'd IntoxioatiG Delirium (292.$1), (292.11), Opioid-Induced Psychotic Disorderh~inations12), Opioid-Induced with Ha l (z9' Mood Disomder (292.84), ~ or Similfgrlacting Arylcyclohexylamine Phencyclidine Intoxication (292.89)x, P} or 1y Acting Arylcyclohexylamine Pherlaycliditx ~ Siwil Intoxication l7elirium.c' lidine r Similarly Acting (292.81), P'h a (1?~CP~
~
Arylcyclohexylamine orlisord~rh Delusions (292.11 Induced Psyc ' ), ~
Phencyclidine (PCP) tiArylcy~lolxylamine IndGtced Psychotic or Similarly , t Disorder with hallucinations)~ encycl~din(PCP) or Si.mil.arly (292.1, ~ Acting Axylcyclohexylamine r2.8A~), .yc~d~e (pCP) or Similarly Mood Disord' Ph Acting Arylcyclohexylarnine 'Disorder..89), Phencyclidine Induced Anx ~ (2~ (PCP) or Similarly Acting Arylcyclohexyl ~telated ier Not Otherwise Specified T)i (292.9), Sedative, 1le Intoxicatii (292.89) ITypnotic or ' Sedation Hypnotic or , , Anxiolytic Intoxication2'l~1), Sedal;ion. yp370'tiC Or Anxiolytic belirium (2 ~ ' Withdrawal Delirium (292.81), ir Anxr:olyti~ duced Persisting Sedation, Hypnc't ~ hementia (292.82), Sedation, i~rtic-lndu~edsyc.hotic Disorder Hypnotic or An . with Delusions D~CST()R: 117613k11 (292.11), Sedation, 'tic-Inducedsychotic Disordex with Hypnotic or An"
I~allucinations (292.12), ~otic lytic-Induced Maod Disorder Sedation, I ~ or Anxi (292.$4), Sedation, itic-Induced.~cietyDisorder (292.89), Hypnotic or An;' ' Other (or .
Unknown) Substance Intoxication9'139}, Ltnktxown) Substance-Traduced ( ~ Other (c Delirium (292,81), Dther Substance-aced Persisting Dementia (or Unloz ~~
(292.$2), Other (or atc-Inducedchotie Disorder with Delusions Unknown) Sub P;
(292.11), Uther (or ai4~In.de~cedlotic Disorder with Hallucinations Unlrnown) Subs P:
(292.12}, Other (or are-Inducedo~.i Disorder (292.84), Other Unknown) Subs, (or ~Tnla~awn) Substance-InducedtDisorder.$~)), ~ (29 Other (or Unlrnown.) Substance Disorder Not p,~fied Obsessive Compulsive Disorder Qtherwise (292.9' (300.3), Post-traumatica(309.81),eralized Anxiety Disorder Stress l:3iso~ I G (300.02), Anxiety Disorder Not ~cied (300.00).c>dy Dysmorphic Disorder Otherwise S (300.7), ' aleurasis).7), Samatization Disorder Hypocltondriasis (or (3C
Hypochondria I~
(300.81,), Undifferentiatedrrpisorder.81), Somatoform Disorder Somato ~~ (3( Not i Otherwise Specif ed .mt ExplosivD isorder (312.3A~), Kleptomania (300.81 ), Intei i (312.32), Pathological 2L), Pyroma(312.33), Trichotillomania Gambling (31 ' (312.39), and Impulse ~et~TOS Schizophrenia, Paranoid Type, Control Disoyl (312.3 {295.30), Schizophrenia,ec'295.10),zophrenia, Disorg ~ I Scl Catatonic Type, (295.20), Scliizaphrenia,ti;- d Type9(1), Schizophrenia, Residual Undifferei {29. Type (295.60), Schizophreniformr95.40), a ffective Disorder (295.70), Disord' ~ Schi .
I
Delusional Disorder sI~otlc ( 298.8), Shared Psychotic (297.1), Brief Dlsor Disorder (297.3}, Psychoticx4e to Medical Condii~ion with Delusio~.~.s Disoxd ~a Gene (293.81), psychotic ageneral al Condition with Hallucinations Disorder Due ti IVIe , , I
(293.82), Psychotic mvise d (298.9), Major Depression, Disorders Not t Specif Single Episode, Severe, without~tares , Major Depression, Recurrent, Psychotic~ (296.2:
Severe, without Psychotic2i.33), Disorder, Mixed, Severe, Features~I Bipola without Psychotic Features (296.63),IBorder, Severe, with psychotic Features I3i.po.l~ ~ Mix (295.64), 'Bipolar Di.sarder,ae, withoutychotic Features {296.43), Manic, Bipolar Disorder, Manic, Severe,o, f'eahn~es6.44), Bipolar Disorder, with Psych ( Depressed, Severe, without Psychotic~2'>.53), Disorder, Depressed, Severe, Faahwes~ Bipoh with Psychotic Features (296.54),rl7isorder~.89), Bipolar Disorder Not Bipol. ~ 1{2 ~UCS-fOir: il7613811 Otherwise Specified (296.80}, Persq' a Ity bisorde aranoid (301.0), Persanal.iiy Disorders, Schi~aid (301.20), Perso ~ IyDisorders, chizotypal (301,22), Personality Disorders, Antisocial (301.7), and P~ ~nality Disar s, Borderline (301.83}.
The term "a patient in uee neatmept" a used herein will refer to any subject or psychiatric patient who c ~r l0.tly has or m dEVelop any of the above syndromes or disorders, including a ' y ymdition or ' cider in which the subj eet spends an exeeasivE amount of time in a shl p ytate or tlnabl to maintain a satisfactory degree o:f wakefulness during a period of the ,~rhecn wake 1 ess is required or desired or has lrZ7S.
Paliperidone, including its ~paceutiaallyaeptable acid addition salts, pl enantiomeric forms and estersa iiministeredr the practise of the preseu,t may invention. Paliperidone is y the described in ~t'.lrS Patent 5,158,952.
well 1rno art and ' As rioted in US Patent 5,158'9.~, paliperldohas basic properties and, conseduently, this compound ~ averted erapeutically active noai-toxic may b, to i acid addition salt forms by : I lh acids, such. as, far example, treatsnen apprapriat inorganic acids, such as hydrohalic~ I' e.,~.ori.c, hydrobromic acid and the like, ' hydroc sulfuric acid, nitric acid, ~ and or organic acids, s'Llch as, for phosphoriq the .
lilt example, acetic, propanoic, c tic, ropanoic, 2-oxopropanaic, hydro 2 hydrox ethanedioic, propanedioic, ' (Z)-2-butenioic, ()3)-2-butenedioic, 2-butanedi i . . ;.
hydrd~cybnta~nedioic, 2,3-dihydrou1j~edioic,, ~ 2-h y-1,2,3 propanetricarboxylic, m.eth.atlestafotlic, ethanesulfonie,I nesulfonic,ethylbenzenesnlfonic, be 4 .
cyclohexanesulfamic, 2-hydroxybe~ ~" ,4-amino-2ydroxybenzoic arid the like acids.
~
Conversely the salt form can o a srd base form by treafioent with be co into the alkali. The term acid addition yd hereinaba also comprises the solvates which salt a such compounds are able to d :iid meant to be included within the form ar..j I solvates scope ofthe present invention.p Is of tes are e,g,, the hydrates, Exa ~ such sol alcoholates and the like.
~
Esters of Paliperidone are ~ i~ in are described in't1S Patent the art ai 5,254,556. P,sters ofpaliperidonecl~~ie 'd, decanoic acid, dndecarlia acid, i octanoi.c a pOCS1'OTt I 17613811 ketxadecauoic acid or hexadecanoici(palmiti; ). The currently preferred acester of paliperidone is paliperidone paImit i Paliperidarle may be formaltol withrmeutical e~ccipie>Gtts into p a variety of . .
dosage forms as described 5,158,92.~peridone will in one embodiment in US P ' of the present invention inan ysaform. Suitable oral dosage be provide oral forms d include but are not limitedlel .releaser dad release dosage forms.
to contra . a Currently preferred are tr;dad age forms_ Most preferred are once daily a relo extended release OROS oral fawas are11 larown in the art. Examples dosag whit of oral dosage forms of paliperidonerascribedn 20040092534, US 20050208132 . U
and US 20050232995.
p'or the practice of this dopaliperiionshould be delivered with a inv dosage form that will provide low nentrationvation (peak to trough) for the plasma c ~ patient receiving treatment to reducevdaykimes1emess andlor sleep disturbance.
exce ~ ' Low plasma concentration m~ans headore variation in plasma variati ' that i concentration (Cmax-G'inin.)h:s beennied. As illustrated in. Figure / Cm ' m '.1 a l.ow plasma concentration variation d by : ge form being tested (specifically is th d between day ~ and 7). The ~r'atioripla concentration from the intrados ~ ' maximum plasma concentrationax) linium plasma concentration (Cmin) (C I to the ~
when minimized reduces excessive a sIe yins and/or sleep disturbance.
rn one embodiment of the invention,ation ismconcentration from Cmax to the r ' :in Cmin p will be less than about ei~rably~ about 30 percent, morE preferably 35 percent, p~ les th~
h-om about 10 percent to ~t, preably from about 15 percent about 30 ~I most to about 25 percent. These aelated(C5ax-Cmin) I Cmax from the ranges are ~ a - administration o:f one to next.rofbly the dosing will be onto dosage form t t per ~Y. ~ ~
I
For the avoidance of doubt ', in adose'° o ~ "ir dose period" refers to the period between the initiation of dnlg rele ~ 1 y a dosa ° fo: . .from. its administration until the administration of the next dose of s ' usage f rm a dosixlg regiment.
Generally, this period will be the period from the a; ~ nistrati.otl of a dose to the administration of another dose, except where a doe;ag' ~: rln does fiat lease drug imanediately upon DOCSTOR; 117GL3811 adnunistrati.on. hi this case, the pe .a of delay of r ease of the drug will have to be considered. This adjustment shoul~b~ considered ia~~establishing Cmin.
Additionally, Figure 1 illust at s a flat plash curve. "Flat plas>ana curve"
means a plasma concentration curve that . ac ies and maim 'ns a substantially constant value after a defined period of time folio " y administrati of a dosage form according to the invention. A steady state wherein t ~e bsolute vain o,f Ctnax and Cmin are relatively canstan.t from day to day is achieve a .er about 6 d: s.
"C" means the concentratio o 'drug in bloo plasma, or serum, of a subject, generally expressed as mass per i ~ v lume, typica nanograms per milliliter.
For convenience, this concentration ma, b ~ referred to .. ein as "drug plasma concentration", "plasma drug cane atr ti.on" ar '~la a concentration". The plasma do-ug concentration at any time foil. ~ ~ ig drug admix stration is referenced as Ctime, as in C9h or C24h, etc. A maximum pla m concentratio obtained following administration of a dosage form obtained directly o the experim tai data without interpolation is rei'erted to as Cmax. A minimum a na concentra ' n obtained following administration of a dosage .fomn. ab i.i ed directly fr ~n experimental data without interpolation is referred Cmin II.
Persons of sI~ill in the a~~ wi 1 a predate the loud plasma drug concentrations obtained in individual subjects will ~ y due to inter atient variability izt the many parameters affecting drug absorpti , 'stribution, tabolism and. excretion. For this reason, unless otherwise indicated, h ~ t a drug pl , as caocentratian is listed, the value listed is the calculated mean value ~ 'd on values l~tained from a groups of subjects tested II.
Those of ordinary s1d11 will that paliperidone, in th appreci its salts, enantiomers, and esters, v~red known uses of risperidane.
can be ad for Far all th example paliperidone a 11 schixaphre~.schizoaffective disorders, can be used to i bipolar mania dr other diseasep ~ychosis,sive behavior, anxiety states in whi aggr or depression is evidenced (e.g. ith dementiapost traumatic stress psychosis associa syndrome, etc.).
As used herein the I;je t", refersanimal, preferably term "su to I a mammal, and.
most preferably a human,cey the (treatment, al~servation who has 1 object or a .
T)0(:S'f'OR: I t7611fl~1 experiment.
The term "therapeuticallya five >'used herein, means rimaurat'that alnaunt of active compound or g t that . a biological ar medicinal pharmaceutical : elicits response in h'mnan that is being rcer, medicaltor or other clinician, sought by a res ' wtuch includes alleviation of the ' or disordereing treated.
symptoms of the di Those of slcill in o.; diseases. easily determine the the treatmer cau effective amount of paliperidonefov the f the diseases listed to administer treatmenabove. In general it is contemplatedc ve amount1d be from about 0.01mg/kg that an eff ' w to abort 2 mglkg body weight. m t ofthe ~t invention, paliperidotte In one embo pres is administered in an toa subjecta day. The mg o:l'compaund oral dosage fo one delivered in such . atient from 0.25 to about 20 a dosage form to a may mg (e.g. 0.25 1 b rng, 0.5 mg, I mg, ',mg,.6 ig, $ mg, 9 mg, 10 mg, 2 mg, 3 mg, 4 m mg, 11 mg, I2 mg, 13 mg, 14 mg, ig, 1$ ~~ng, and 20 mg) per 15 mg, I6 mg, 1 sng, oral dosage form.
'~ ~ ~ ~ -DOCS'I'UK: 11761381 ExAlvr:PraF y Psliperidone Cspsul~ Shaped T'ablet~'r'rilayar 2 mg System A dosage form adapted, d and an osmotic drug delivory des shapE device was manufactured as ~ paliperidane325 g of polyethylene follows: 120 oxide with average molecular weight, d 2000 odium chloride, USl' of 2DD,0 g o were added to a fluid bed granulator~ ~der as prepared by dissolving bowl. Next a solution400 g of hydroxypropylmethyl ~ ed as ' g an average viscosity cellulose id 2910 of 5 cps in h '7,b00 g o.f water. a fluid >.nulated by spraying The dry rx~.aterial.s bed with 4,000 g of binder solution. Next,t on was i the granulatar to the wet gran dried an acceptable moisture content, and p ssing a 7>>nesh screw. Next, sized using b throu the granulation was transferred r and 'th 5 g of butylated to a b1a mixed hydroxytaluene as an antioxidant and 5 g of cid.
lubricated wi stearic Next, a second drug nt campositi~ was prepared as follows:
compa 2$0 g of paliperidone and 9165 a oxide verage molecular weight g of polyeth with of 200,000 were added to a fluid b wl.. . der solution was prepared bed granulato Next by a b dissolving 400 g of yl celluloseentified as 2910 having hydroxypropyl i an average viscosity of S cps . E dry were fluid bed granulated in 7,600 g of wet mat by ~
spraying with 4,000 i n. Next,t granulation was dried g ofbinder sox the in. the gtanlulator to an acceptablec >ateut, d using by passing through moister ~ and a 7-si mesh screen. Next, transferreda blender and mixed with the granulation S g of butylated hydroxytoluenexiant and,.ated with 50 g of stearic as an anti lubr acid.
Next, a push composition epared ows: fast, a binder solution W as fo was prepared. 15.6 leg i one identifiesas K29-32 having an average ofpolyvinylpyrr ~
molecular weight of l ed in ~ of water. Then, 24 kg 40,000 was dis 104.4 of sodium eh.l.oride and 1.2 sized Quadro Comil with a 21-mesh kg of ferric oxide using screen. Then, the screened d 88.44 olyethylene oxide {approximately material ~ kg of 7,000,000 molecular d to d ganulator bowl. The dry weight) were a fluid materials were fluidized ile 4G.2cinder solution was sprayed and mixed kg o from 3 ~
nozzles ants the powder.a ion was n the fluid-hed chamber The gran I dried to an DOC99y7R: 117617811 acceptable rnoistttre level. The coated l;ranules ware ~~ued using a Fluid Air mill wikh a 7-mesh screen. Tl~e granulation was transfeiTed to a t to tumbler, mixed with 1 S g of butylated hydroxytoluene and lubricated with 29A~ g lagnesium stearate.
Next, the paliperidone drug compositions fo fihe first and the second compartments and the push composition were pomp ~;ssed into trilayer tablets.
first, 50 mg of the paliperi.dan.e compartment one compositio was added to the die cavity and pre-compressed, then SO mg oftlxe paliperidone co paxtment two composition vsras added to the die cavity and pre-compressed, then 10 mg of the push campasition was added and the layers were pressed into a 3116" diem ~er longitudinal, deep concave, trilayer arrangement.
The trilayered arrangements vvene coated wi ~ a subcoat laminate. The wall forming composition comprised 70% bydroxyprapy pellulase identified as EF, having an.
average molecular weight of 80,000 and 30% ofpol 'nylpyrrolidone identified as T~29-32 having aJ.~. average molecular weight: of 40,000. 7 ne wall-forming composition was dissolved in auhydrous ethyl alcohol, to rnalce an 8°/ ~~olids solution. The wall~forming eompositiou was spxayed ante and aro~~nd the bilay ed arrangements in a pa~.~
water until approximately 20 mg of laminate was applied t each tablet.
The trilayered arrangements were coated with a semi-permeable wall. The wall farming campasitian campri.sed 994/° cellulose aceta ~ havin.g a 39.8%
acetyl content and 1%~pal.yethylen.e glycol comprising a 3.350 viscosi -average molecular weight.
The wall-forming composition was dissolv~;d in an aceto e:water (95:5 wt:wt) co solvent to make a 5% solids solution. The wall-forming coynp pition was sprayed ante and around the bilayered vrxangements in a pan ca;tter until ppp ximately 40 mg of membrane was , applied to each tablet.
Next, two 25 mil (0.6 mm) exit passageways yvere laser drilled through the senli-permeable wall to connect the drug layer with the ex eriox of the dosage systm. The residual solvent was removed by drying far 144 hau s at 45 °C and ~5%
humidity. After drilling, the osmotic systems were dried for 4 holes ~~ 45 °C to remove excess moisture.
"fhe dosage form produced by this manu,factt 'e was designed to deliver 2 mg of paliperidone iu an ascending delivery pattern from o drug-cantai.ning cores.
The firsi DOCaTOR; 117fi13f;11 core contained 1.2% paliperidone, 73.25% polyethylene oxide possessing a 200,000 molecular weight, 20% sodium chloride, USP, S% hydroxypropylmethyl cellulose having an average viscosity of 5 cps, 0.05°/a butylated liydrcyytoluene, and 0.5% stearic acid, The second. drug core contained 2.8"/o paliperidone, 91.65% polyethylene oxide possessing a 200,000 molecular weight, 5% liydrox3~ropylm.ethyl cellulose having an average viscosity of 5 cps, 0.05% butylated hydroxytoluene, and 0.5% stearic acid. The push corxsposition comprised 73.7% polyethyletle oxide comprising a 7,000,000 molecular weight, 20% sodi4un chloride, S% polyviv~lpyrrolidoae possessing an average molecular weight of 40,000, 1% ferric oxide, 0.05% hutylated hydroxytoluene, and 0.25% magnesium stearate. The semi permeable wall was comprised of 99%
cellulose acetate of 39.8% acetyl content and 1 % polyotllylen~ glycol. The dosage form comprised two passageways, 25 mils (0.6 mm) on the canter of'the drug side.
EXAMPLI~; 2 Paliperidone Capsule Shaped Tables, Trilayer 3 mg System A dosage form adapted, designed and shaped as an osmotic ding delivery device is manufactured as follows: 2.246 kg of paliperidone, $7.2 kg of polyethylene oxide with :average'molecular weight of200,000 and 2~. kg of sodium chloride, trip are added to a fluid bed ~raaulator bowl. Faliperidone amovat includes a 4% manufacturing excess to compensate for losses during processing. ~e~, a binder sol.utinn is prepared by dissolving 7.2 kg ofpalyvinylpyrrolidone identified as X29-32 having an average molecular weight of 40,000 in 52. $ kg of water. The dry materials are fluid bed granulated by spraying with SO kg ofbinder solution: Next, the wet granulation is dried in the ganulator to the acceptable moisture content. Then, the dried granulation is sized using a Flitid Air mill with a 7~mesh screen. The grapulation is transferred to a tote ttmzbler, mixed with 60 g of butylated hydroxytoluene and lubricated with 600 g stearia acid.
bOC&TOR; 117EtSBlI
Ne~ct, a second drug compartment composition is prepared as follows: 5.242 kg of paliperi.done, 0.06 kg ofyellow ferric oxide and 108. kg of polyethylene oxide with average molecular weight of 200,000 are added to a fluid bed granulator.bowl.
Paliperidone amount includes a 4°/a manufacturing excess to cori~pensate for losses duristg processing. Next, a binder solution is prepared by dissolving 7.2 kg of polyvinylpyrrohdone identified as K29-32 having an :average molecular weight of 40,000 in 52.8 kg of water. The dry materials are fluid bed ~;ranul.ated by spraying with 50 kg of binder solution. Next, the wet granulation is dyed in th.e granulator to the acceptable moisture content: Then, the dried granulation is sized using a lr laid A.ir mill with a 7-mesh screen. The granulation is transferred to a tote ~utnbler, mixed with 60 g of butylated hydroxytolvene and lubricated with 600 g s~keatic acid.
Next, a push composition is prepared as follows: first, a bidder solution is prepared. 30 lcg of polyvinylpyrrolidone identified as X2.9-32 having an average molecular weight of 4D,000 is dissolved in 200.8 kg of water. Then, 100 kg of sodium chloride and 5 kg of red ferric oxide are sized using a Quadro Comil with a 21-mesh screen. Then, the screened materials and 368.50 kg of. Polyethylene o~cide (approximately ?,000,000 molecular weight) are added to a fluid bed granulator bowl. The dry materials are fl,uidized arid mined while 192 kg ofbinde~ soluti~pn is sprayed tom 3 nozzles onto the powder. The granulation is dried in the fluid-laed chamber to an acceptable.moisture level. The coated yanules are sized using a >~luid Air mill with a ?mash screen. The granulation is~transferred to a tote tumbler, mixed with 240 g of butylated hydroxytoluene and lubricated with 1240 g stearic acid.
Ne~ct, the paliperidone drug compositions For the first and the second ' r corrrpartmettts attd the push composition are compressed into trilayer tablets. First, 30 mg of the paliperidone compartment one composition is added to the die cavity and pre-compressed, then 54 mg ofthe paliperidono compartment two composition is added to the dic cavity and pre-compressed, then 140~mg of the push composition is added and the layers are pressed into a 3116" diameter lou,gitudinal, deep concave, irilayer arrangement.
oocsrotr; mstzsvr The trilayered arrangements axe coated vUith a subcaat lami.n.ate. The wall forming composition comprises 95% hydroxyethylcellulose and 5% ofpolyethylene glycol comprising a 3.350 viscosity-average ro.r~lecular weight. The wall-forming composition is dissa.lved in water, to make an 6P/° solids solution.
The wall-forming composition is sprayed onto and around the bil~yerec~ arrangements in a pan caater until approximately 10 mg of lai:ainate is applied to each tablet.
The trilayered arrangements are coated with ~ semi-permeable wall. The wall forming composition comprises ~9~% cellulose ~cetata having a 39.8% acetyl content and 1% polyethylene glycol comprising a 3.350 viscosity-average molecular weight.
The wall-forming composition is dissolved in an ac~ton.e:water (95:5 wt:wt) co solvent to make a 5% solids solution. The wall-forming composition is sprayed onto and arovmd tlxe bilayered arrangements iaa a pan coater untillapproximately X45 mg of membrane is applied to each tablet.
Next, two 25 mil (0.64 rnrxi) Exit passageways are laser drilled through the semi-permeable wall to connect the drug layer with tlfe exterior ofthe dosage system. The residual solvent is removed by drying for 144 hours at d.S °C and ~5%
hmnidity followed I I
with approximately 1 hour at 45 °C to remove e~ces~ tlloisture.
The dosage farm produced by this rnanufl~ctur~ is designed to deliver 3 mg of paliperidone in an ascending delivery pattern from tv~a drug-containing cores.
Pnliperidone ~'apsnle Shaped Tablet, Tr.ilayor ~ mg System A dosage form adapted, designed and sllape~ as aroL osmotic drug delivery device is manufactured as follows: 6.64 kg o~paliperido~Ie, 8285 kg afpolyetloylene oxide with average molecular weight of 200,000 and 24 kg. of sodium chloride, ~(.TSP are added to a fluid bed granulator bowl. Paliperidane amaun~ includes a 2.5% manufacturing excess to compensate far losses during processing. N~ext,~a binder solution is prepared by dissolving 7.2 kg oCpolyvinylpyrrolidoue identified ~s 1C29-32 having an average molecular weighLt of 40,000 in 52. & kg of water.; The ~lry materials are fluid bed 16 ~
DOCSTOk: 1 L7613811 'I
granulated by spraying with 50 kg of binder solution. Next, the wet granulation is dried in the granulator to the acceptable moisttue content. Then, the dried granulation is sized using a Fluid Air mill with a.7-mesh. screen. The grapulation is transferred to a tote.. .
tumbler, mined with GO g of butylated hydroxytoluenw and lubricated with 600 g stearic acid.
Next, a second drug compartment composition is~prepared as follows: I5.50 leg of paliperidone, 0.01$ >~g ofblack iron oxide, and 98.20 kg ofpolyethylene oxide with average molecular weight of 200,OOU arE added to a ilttid bed granulator bowl.
Paliperidone amount includes a 2.5% manufacturing gxcess to compensate for losses during processing. Next, a binder soluti.an is prepared by dissolving 7.2 kg of polyvinylpyrrolidane identif ed as 1029-32 having an average molecular weight of 40,000 in 52.8 kg ofwatex. The dry materials are fluid bed gt~a,nulated by spraying with 50 kg of binder solution. Next, the wet granulation is dried in the granulator to the acceptable moisture cor»tent. Then, the dried granulation is sixec~ using a Fluid Air mill with a 7~
mesh screen. The granulation is transferred to a tote tumbler, mixed with 60 g of butylated hydroxytoluene and lubricated with G00 g sxearic acid.
Next, a push composition is prepared as follows: first, a binder solution is prepared. 30 ltg ofpolyvinylpyrrolidone idenfiihed as K29-32 having an average molecular weight of 40,000 is dissolved in 200.8 lcg of water. Then, 100 kg d:f sodium chloride and 5 kg ofred ferric oxide are sized using a.Quadro Comil with a 21-mesh screen. Then, the sc~~eened materials and 368.Sp kg o;f Polyethylene oxide (approximately 7,000,000 molecules weight) are added to a fluid bed granulator bowl. The dry materials are fluidized and mixed while 192 leg of binder solution is sprayed from 3 no:ccles onto the powder. The granulation is dried in the .fl.uid-bed chamber to an acceptable moisture level. The coated granules are sized using a Fluid Air mill with a 7-mesh screen. The granulation is transferred to a tote tumbler, mixed with 240 g o,f butylated hydroxytoluene and lubricated with 1200 g stearic acid.
Next, the paliperidone drug compositions for the first and the second compartments a~~.d the push composition are compressed into trilayer tablets.
First, 50 mg of the paliperidone compartment one composikion is added to the die cavity and pre-compressed, then 50 mg of the paliperidone compartment two composition is added fXICSTOR: i 17613811 to the die cavity and pre-compressed, then 100 mg of the push composition is added and the layers are pressed into a 3/16" diameter longitudi»al, deep concave, trilayer arrangement.
The trilayered arrangements are coated with a subcaat laminate. The wall forming composition comprises 95°~o hydroxyethylce;[lulose and 5%
ofpolyethylene glycol comprising a 3.35p viscosity-average molecuhr weight. The wall-forming composition is dissolved in water, to make an 8% sal'ids solution. The wall-forming composition is sprayed onto and around the bilayered arrangements in a pan.
canter until approximately 10 mg of laminate is applied. to each tyblet.
The trilayered arrangements ors coated with a semi-permeable wall. The wall forming composition comprises 99°,~° cellulose acetate having a 39,8% acetyl content and 1 % polyethylene glycol comprising a 3.350 viscosity-average molecular weight.
The wall-forming composition is dissolled in an acetone:water (95:5 wt:wt) ca solvent to make a 5% solids solution. The wall-forming cam.pas.itian is sprayed onto and around the bilayered arrangements in a pan coater until approximately 45 mg of membrane is applied to each tablet.
Next, two 2S mil (0.64 mm) exit passageways are laser drilled through the semi-permeable wall to connect the drug layer with the exterior of the dosage system. The residual solvent is removed by drying for 144 hoiu's at 45 °C axed 45%
humidity followed with apprQxinnate 1 hour at 4S °C to remove e~ccess moisture.
The dosage form produced bn ilus rnaaulacturs is designed io deliver 9 mg of paliperidone in an ascending delivery pattern from two driGg-contnitung cores.
3~OCS'fOR: I 17G138S1 rierermi~nation of )Plasma Parofile of ~alipe~idone OROS farmttlation Dosage and Administration RISPER1DAL~ (risperidone iR) brand risperi.don.e vas administered to subjects (in these examples the subjects are human patients). 'fhe initial dose of risperidone was 2 mg/day and titrated to 4mglday an Day 2. Because tho bioav,ailability of ER OROS
paliperidone is approximately 30% that of an oral solution ofpali,~erid.one, l2mg ER OR4S
paliperidone dose was selected to be administered as!an equivalent dose with.
respect to plasma levels to 4mg 1R risperidone. The >3R OROS ~aliperidone was provided as 2mg-tablets made substantially as described in Example 1.
Subjects in each group were given a once-daily oral dose, consisting of six (6) 2mg capsules, every morning daring the washout anc~ double-blind treatment periods.
Shady medication was administered sitting in att upright position with 200m1r, of water immediately after a standardized breakfast eaten. between approximately 8:00 a.m. and l0:0o a.m.
Study Evaluations Subjects were required to complete a washou~ period prior to participation in the study. Subjects who successfully completed the washout period atzd continued to meet eligibility criteria were randomly assigned. in equal n~xmber to one of three treatment groups (tbe results of two the treatment groups are provided in this example);
(1.) Paliperidon.e OROS or (2) risperidone immediate rel' ase. During the double-blind treatinent please (days 1 td 6) , sittdy medication was~administored after a standard breakfast. AlI meals during the study, including the vjr~ashout anal treatment periods, were standardized, consisting of a normal sodium diet with approximately 2,500 Kcal per 24 hours. The subject's total fluid intake was monitored and was not to exceed 3,000 mL
per 24 hours. Subjects were to have no more 'than 3 an.ethyIxanthin-containing beverages(e.g. cola, tea coffee) daily. Soft drinks w~re permitted as long as they did not ~ocs~roa: ~ i7s»su contain quinine ar caffeine and did nol: increase the permitted total daily calories allowance. Other foods including chocolate, grapefrpit, grapefn>,it juice, Seville oranges and quinine-containing beverages were not allowed. Strenuous physical activity was not permitted during the study.
Pharmaculdnetic Evaluations At time points during the double-blind tree 'ent period. until the end of the study on Day 7, blood samples were obtained for measv ent of risperidone, paliperidone and active moiety concentrations in plasma. In each treafiient group, a venous blood sample of S nnl, was drawn to obtain about 2 tn 3mL o:f plasrj~a. The Collection schedule was as follows:
On day 1, immediately before dosing at~d at ~, 2, 3, A., 6, 8, 12, 18, a;nd 22 hours postdose:
W Aay 2 through Day ~, immediately befor dosing and at 2 and 22 hours postdase;
i On Day 6, imynediately before dosing and at ~, 2, 3, 4, b, 8, 12, 18, 22, and hours postdase (on Day 7).
Plasma concentrations of risperidone and pal~perid~one were determined by using a validated liquid cvromatography coupled to mass s~~yoctrometry/mass spectrometry, method.
For the subjects rvho received IR risperidone,;the active moiety concentrations were calculated as the sum of the risperidane and paliperidone concentrations.
L'1f)LS7QFt: l 17fi1381!
. - Sleep >Stu~dy i Purpose: Nighttime sleep disturbance and daytime drowsiness are common in patients witli schizophrenia, and can be a significant concern. far patients tlzai is net always effectively addressed with pharmacolqgic treatment.'faliperidone exte~~ded-release tablet (paliperidone IJR) is an investigational. psychotropicl~tipsychotic agent, with once-daily dasittg, that bas been shown to be efficacious and waI'lll-tolerated in 6-week Trials of patients with schi~ophreniat'3. Effects ofpaliperidon~ ER on changes in. sleep architechtre (Dataset 1) were studied in patie~~.ts with schizophrenia~.relatad insomnia, and the clinical importance of these findings was further assessed by patient-rated changes in quality of sleep and daytime drowsiness (Dataset 2) in patients with schizophrenia.
I
Methods: Data were collected in multicenter, doabh-blind, randomized and placebo-cantroll.ed studies in patients with either stable (Data~et 1) or acute (Dataset 2) schizophrenia. Tn I7ataset 1 (n~2) paliperidone ER ~mg ar placebo were administered daily for 2 weeks. Polysomnography (PSG) variables were assessed afi baseline and endpoint. Other sleep measures included Leeds SleeR Evaluation Questiannsire (LSE.
Dataset 2 (n=1326) was a post-hoc analysis of pooled data .from three, G-week studies'-' with paliperidone ER 3mg, 6mg, 9mg, l2mg, 1 Smg, nor placebo daily. The paliperidone ER capsules were prepared as described in Exatr3ple yu~d 3 above. Patients dosed with.
5mg were provided with two 3mg tablets. Patients dosed with l2~mg were provided with one 3mg and one 9mg tablet, Patients dosed with lStirg were provided a 9mg and two i 3mg tablets. Subjects completed Visual Analogue Sale (VAS) assessments of sleep q~.valiiy ('How well have you slept in the past 7 night?') and daytime drowsiness ('How often have you felt drowsy in the past 7 days?').
I
Results: Dataset 1 analysis set {n~36) consisted of 6'~4/o male, mean~SD
age=32.2yt7.3, baseline meantSD PANSS total score=62.9111.2, mean PSG measured latency to persistent sleep of S8.7~45.8 minutes, sleep onset lat~ucy of 49.~~41 _1 minwtes, at~d a severity o.f insomnia confirmed by a baseline mean deep Ef&ciency Index (SEA
of UOCS'I'OH: t17613fl11 7b~:13.4%. '.Treatment with paliperidone ER resulted rn clinically robust and statistically significant improvements in. sleep, including decrsas~s in latency to persistent sleep (41.9-X23.7 minutes) and sleep onset latency (35.92 .6 minutes). SEI was improved (77.515.6%), total sleep time increased (370.474.3 minutes), Stage 11 sleep duration increased (219.3152.5 minutes), and REM sleep dur Lion increased ($O.1f24.6 minutes).
Pali.peridone ER was witliout significant effects~on slew wave sleep. No statistically significant difference was observed, for any ehatlge ir+ LSEQ scare. The clinical relevance of these findings was supported by Dataset 2 (TTT set: n=1.306, 62%
male, mean~SD age~38.1y~10.9, baseline meaWSD pAN 'S total score=93.5111.8). A11 S
doses ofpaliperidane ER provided s.ignficantly grea cr improvements in quality afsleep compared with placelao, as rated by VAS assessment (mean~SD baselinelchange at endpoint: palipetidone ER 3mg=56.4~28.819.Ot3~.:5; paliperidone ER
fimg=53.5~30.3/11.1~33.7; paliperidone ER 9ixig=SG.5~28.7I11.4~33.0;
paliperidone ER
I
l2mg=55.7~28.0/9.7~33.7; paliperidone ER 1 Smg=53.2~29.1111.3a:33.2;
placebo=52.4~29.310.6t35,9 [p~0.U5]). No signific it daytime drowsiness was associated with paliperidone ER t~~eatment (mea,n~Sl~ baseline/change at ettdpaint:
paliperidone LR 3mg=29.4t26.6/-2.928.1; palipera~an,e ER 6~.ng=28.325.1/-0.927.9;
paliperidone ER 9mg=31.Sf27.3/-~..1~32.4; palaperi lone ER l2mg=32.526.81 2.9131.0; pal.i.peridane ER l5mg=3$.5130.31-3at3 .5; placebo=32.3127.3!-3.030.0 ~p~a.os]).
i Conclusions: '1~hese studies suggest that paliper~dan~ ER treahn.ent resulted.
in improvements in sleep architecture and sleep continu'ty and. patient-rated sleep quality without producing or e~cacerbating the daytime draw mess that is typically open associated with therapies effective for the treattr~ent f insomnia.
References 1. Marder S, et al. Neurapsychapharmc~coi 2005; 3p: S2Q0 2. Kane 1, et al. Neuropsychopharmucol 2QQ5; 30: 5191~I-2 3. Davidson M, et al. Schiaophr Res 2006; 81: S43 1?OCST072: 17 761351
AND/O~ JiL'"XCFSSIVE IJA~E L,E,~~'PINIfr ~hT PSYCfI~ATRIC PAT '~.~.'NTS
~ III
This Invention relates to the ty~of p~liperid ' for the treatment of persistent sleep disturbances andlor excessive ~ ime'~ sleepin , in psychiatric patients.
Patients with mental illness ci~ ~ halve sleep °y.urbances including insomnia, and I
excessive sleeping. Sleep disturbances are common patients with schizophrenia, depression and bipolar disorders. rorie am~le, patie ' with schizophrenia appear to have lvnge~t sleep latency, a higher xty ber ~ f arou dwing sleep and increased periods of wakefulness after sle asset cons ~ ed Pith than ~1 non s chiatric control an s.
eP ?~ p y ~ p (Tondos et al. and Miller at al.). 1'ati~ .tS b+~ing trea ~ Far psychotic symptoms utay also suffer ~rom excessive daytime sleepp~e~s orl drows' v associated with both sleep disturbance and sedation caused by ant psy'hotic m Iyations. Additionally, the excessive sedation caused by souse ari syr~totic m I ations can result in impaired cogtitive functions and other sympto~7r ~th~t interfe. Nith successful treatment of the patient. More importantly, sedation c impair a pa , t's quality of life and efforts to lead a normal life. . I . .
r We have discovered that, by ' ting psychi.t ~: patients who suf~'er .from excessive daytime sleepiness and/or ~ eepl~ disturb ~ with a pharmaceutically effective amount of paliperidone, its pharmaceu ically accept ~u acid addition salts, enantiomeric forms, and esters, delivered at a relativ l.y clPnstant 1 ' ma level, these patients will have significantly reduced daytime drawai~ ss a~dJor sle ' disturbances.
W one emboclirnent, the presep iity,~lntion pr ales for the use of a pharmacoutical composition comprising a therapet~oa~ly e:~fective ~ uut of paliperidone, its pharmaceutically acceptable acid a~d~it on salts, ena ~lmerie forms, or esters thereof, together with a pharmaceutically acc~p~tahlg carrier, the treatment of excessive DOCSTOR 117613$11 daytime sleepiness and/ori ~ance luatric patient iri rie~l a sleep dis in a~ thereof, the ps pharmaceutical composition; .relativelyplasma concentratiaxl providir~ ' 1 variation of paliperidane to the "need ~eut.
psychiatric patien of tre )'n yet another embodiment, resent n provides ;for the rise tl rove of a pharraaeetttical compositionr a therapetttiIly effective amotmt of, compris paliperidorie, its pharmaceutically~ 'table Lion salts, enantiomeria tic ' acid forms, or a esters thereof, togetherc pticallyable carrier, in the preparation with a pharm acts of a medicament for the treatment, v,~ daytime.~piness andlor a sleep of exc . distttrbaace in a psychiatric patient p.e pharmacgoal composition providing in need there a relatively low plasma : anon ~idane to the psychiatric concentration ' of pali patient in need of treatment.
rn another embodiment, ration a pharmaceutical composition the it provid ' comprising a therapeutically attnt ~ridone, its pharmaceutically effectiv of p acceptable acid addition, eric ~sters thereof, together salts, enanti 1 :forms, with a o pharmaceutically acceptableI the tieatiari.f excessive daytime sleepiness carrier, f and/or a sleep dishirbancet 'c patient~ed thereof, the pharmaceutical in a psycia in composition providing p lasma ration variation of paliperidone a relatively 1 cc~na to the psychiatric patienti nt.
in need oftreai a In another emboditnent, tion for the use of a pharmaceutical the j pravid composition comprising a therapeuta ~ r y effectiveotuit of paliperidone, ~ its l .
pharniaceuti.cally acceptfible~ n salts,omeric Forms, or esters acid ad i en thereof, together with a pharmaceutically' ble carrier,r improving sy111ptoms of schizophreiua in a psychiatric. rieed wherein the symptoms are patierl v'..thereo selected from the group consisting bauces ~:assive daytime sleepiness, of sleep da anti the .
pharmacrrutical composition~ relativelyplasma concentration variation pT4V.ld1 " 1 o.f paliperidona to the ' .need lent.
psychiatric pati 1. l of'tr l In another embodiment, Lion for the 'use of a pharmaceutical the :i n 1 provid composition comprising . y affectiveaunt of palaperidone, a therapeuti " ~ iks pharmaceutically acceptablep rt salts,omeric forms, ar esters acid ad i en lhereo~
together with. a pharmaceutically able the manufact'eue of a ace ~ carrier,medieatment fox irnprovirig symptoms is in kris patient in need thereof, of schizop r a psych PUC.STOCt 11?613S1i I li~i i. il wherein the symptoms o ~ the sisting ofsleep disturbances are selected group and excessive daytime sleepiness, ~ceuticalosition providing a the p cc relatively low plasma concentration - ~ridonc sychiatric patient variation of p to tl in need of treatment.
In still another embodiment,~ ;invention'des a pharmaceutical 1, composition comprising a therapeuticallyy cant eridone, its pharmaceutically effecti of p:
acceptable acid addition~ uric stets thereof, together salts, en.ant farms, wi.tta a pharmaceutically acceptable~ ~ impmvingptoms of schizopbrenia carrier ' in a psychiatric patient h ~oit~. ~s are selected frorn in need thereof, the the group syn consisCing of sleep ~ ~4ssivo sleepiness, the pharmaceutical disturbances and days composition providing ~lasrr~ tration variation of a relatively 1 con paliperidone to the psychiatric patient~ e~nt.
in need of tre Tliese and other obj ~dantages resent invention rt'1ay ects and of c be appreciated from a ~ applicatim review of the p I
Figure 1 provides a graphie~.~ lu~esentation c~~~ relatively constant plasma release pm.ftle of, paliperidone from 1drelease e'form such as an OROS dosage a contr do form as compared to an immediate1~se form iperidone. The data paints shown ~ of , for day 1 are measured at specific~-intervalsescribed in Example 4. p'or days ti as 2 through 6, data points were me ~t 2 and s.post administration and constitute 2~ h an average of the results from ~,p at ' The data points for paliperidone each each , ti shown between days 6 and 7 shoalaiple times during tha day, illustrating ~ tp~ . the intraday variance in plasma level , tration~peridone.
c ~ of ~
Sleep dishtrbances axed exec Isi !~ daytime il siness occur in patients suffering from many mental illnesses. These I~u ~jects spend excessive amount of time in a sleep UOCS"COR: 117b 13811 I >I' I 6 state or unable to maintain~ ~ pie efixlness during a period of the day a satisfa o;. ~ ee of when wakefi>_lness is required~ I
or de I
As used herein the Term Iap!at>q baqce'ha7.1 mean a condition in which ate "sl ' individual has longer sleep I f ~usals during sleep, anal latency, i ;her number~
increased periods of wakefulnessIr.~r~ ep onset. ~ypersomnia, dyssomnia and a ~ ~ t~
parasomnias). These disorders~ ~ iiagnosedg conventional methods such as ma b a are commonly employed in uto, iy ~somnography).
a sleep (e.g.
t As used herein the term a ~ ve ~ 1epiness" (EDS) shall be used "E ' aytim ; I
interchangeably with the 1 ' oaf c f" and shall mean a cotldition in term '~a . spnzno t which an individual feels i ~. ariyg d finds it di.;fficGVlt to resist the very dro y the d~~ i 'loge to fall asleep, whether 1 ivir~ualtxen enough nighttime sleep.
or not ha;
' Bxcessi.ve da me slc inESSi ' ~:.flztled TD I as s:l jness occurring in a situation yti ep ( ;
when an individual would ~ be awaked alert. Clinically the symptoms of be expec :
EDS can be quantified and ~ i, ~ vafietyys, including but not limited toy measur i of I I
~ ' the Multiple Sleep Latency l.[' (S in MA and Dement WC, Sleep Test ~e Cars ~
19$2;5 Suppl 2:567-72) , ~ ce ~f mess Tast (MWT) (See, Mitler the M ' I~Walct-I
-MM, et al. Elecirr~encephalogrp I i Cli rola~ysiWl,2;3(6);65$-61) or the StauGord I
Sleepiness Scale (SSS) (See,~ ;t a~ )tysiology, 1973;10{4):431-b) (gee Todd ~I, Fs~re)n also, Arand D et al. Sleep,) 3-1' ). causes of EDS are multiple and the 2005;28 . T7 ~
,, use ofthe term EDS hereina d i ~ ypartipular cause or etiology.
is not i ~ Idly ' People with E'DS frequentlyp a fa 1. situations where they need or ' doze,. ' asleet ~
want to be fully awake and a ~ ~Igri made wlien the symptoms of FrDS
alert. ~ sis can interfere signi~.cantly ~ Lity t>rate and perform daily tasks and with a pers I to cpnn routi-nes such as work, ' I iti~ a, car or operating othor hazardous family reap , drivi~ -machinery or general. quality of lif I
The term "psychiatric patiot'. d hereiefers to a human, who has .been the ~
object of trcatnxent, or a ~ lleia~aIr!', and tha term "mental disorder"
cxpcrinxent fq , di!sor ( , ~ Cer~ rll'orrided in the Diagnostic and a~Iso encompasses mental to tho:, illnesses I
Stafiistical Matlual (DSM ~nc P~yclogical Association (APA). These III or N) I
mental disorders include a ~ pal ~ other disease states in which sclxizophr . di$oa ' psychosis, aggressive behavior,ty~ de~ ~videneed. Schizophrenia refers to arlxi ' 1 ~pressio~~
17UC5'CC~R: 117413811 conditions characterized schiza(fec~ e~disorder anal schizophreniform as schizoph>n disorders, in DSM-IV-TR ~ I3 ~ oll Disorder refers such as cal: 295. to a conditions characterized as a n SM-I-TR , ch as category 296.xx Bipolar Disorder,' ~ including ~
I3.ipolar 1 and Bipolara ~SM--l~ prepared by the Taslc Disorder II. Force on Nomenclature and StatisticsI Ficanyclii'c Association, and of the ~ . P provides clear j descriptions of diagnostic ~tholo'c , ological conditions, categorie ~ ps which are psychoses or may be ~choticfeats include, but are associated wi not limited to the following disorders , icteriin ~ DSM~1V-TR. Diagnostic that have been. c ' t and Statistical Manual r,'Revise, d. { 1994). The numbers of Mental Disord ~ i 3r in parenthesis refer to c~Glrgorie'~'her ')led artisan will the DSM-N-T recognize that there are alteniative , ~logiesand ~ siFcation systems nomenclatures, c for pathologic psychological conditionss ystemevo.~ wi.th .medical scientific and that th ~ progress.
Examples of pathologicisgiaalondins which may be treated ps ! ~ include, but are not limited ~ datio{31 Moderate Mental Retardation to,. Mild Mental (318.0), Severe Mental~ ~.1),fo Mental Retardation Retardation ;> (318.2), Mental Retardation fi(319Acs ~ is Disorders (299,00), Severity Unspe a ~ v Rett's Disorder (299.$0), ~ tivesord~ 299.10), Asperger's Childhood Disin D Disorder ~~ ( (299.80), Pervasive i ordert ~ rwise Specified.{299.$0), Developmental ~ O
Attention-Deficit/Hyperaciivityr<!'r in.eda (31.4.01), Attention-Dis~l Cam DeficitlHyperactivity n jlately~~ttev 've Type (314.00), Disorder Pred' i Attention-De~eit/Hyperactivity ~Il~atclyIype: tjve-Impulsive Type Disorder Pred' (314.01), ~
Attention-Defieit/Hyperaetivity 'r (314.Conduct Disorder ( Dis NOS Childhood-i Onset and Adolescent ! psitionhe ~ t Disorder (313.81), Type 312.8) Disntptive Behavior Disorder Not e ~ 2! . olitary Aggressive Otherwise S; p iIf 9), Type (312.00), ed (3 Conduct Disorder, Undifferentiated ~e 90),urette's Disorder (307.23), I (312 Chronic Motor Dr Vocal Tis 2 ~'ra~nsit jsorder (307.21), Tic Disorder (307. Ti Disorder NOS (307.20), Alcohol ~ ~irium291.Alcohol Withdrawal Intoxicati Delirimx'L
(291.0), Alcohol-InducedD ~entia291.' , Alcohol-Lnduced Persisting ~ Psychotic Disorder with Delusions (291.5), A1 ~ t;~1-Indu ed ; chotic Disorder rwith Hallucinations (291.3), Amphetanui ~~s a~ Sxmil ly ity Sympathomimetic Into~cicatior~
(292.89), Amphetamine or Sinularl~~ I,ling S pa. ~ mLimetic Delirium (292.81), DOCSTOR: 1 L7ti1.38\I
Amphetaznine or Similarly'"athomi~etiinduced Psychotic with Acting ~' ~~~iag Delusional (292.11), Amphetamine dSympa unimeti.c Induced Psychotic or Similarl ~ r'I ed with Hahucinations (292.12),'uPsychati Disorder with Deh~sians Cannabis~I dith HalIucin(292.11),-.
Car~na>5is-Induced ~;~ (292.81),fans (292.12), Cocaine Psychotic Disor ~C Intoxication (292.89), Cocaine Intoxication'red Psychoti;sine-reduced Psychotic De ' r~~:$9), Disorder with Delusions (292.11), rIal~uci disorder with Hallucinations Cocaine- ~~ 'c ogee Intoxication Delirium (292.12), Halluciogen disorder th belusions (292,11), Intoxication ~ gas (292.12), Hallucinogen-.induced (292.81), Hallucinogen-Induced .~ with Pa ; Delu hallucinogen-Induced Psychotic di Mood. Disorder (292.84),ez;Ilnduced~ty Disorder (292.89), )"rallucino ~
Hallucinogen-Related erwi.se eci (292.9), Inhalant Disorder Note' Spec Intoxication (292,89}, Inhalant 'u~ (292,$1;x,slant-Induced Persisting Intoxication Deli ' Dementia (292.82}, Inhalant-Lnduced ;sorder elusions {292.11), Psychat' with Inhalant-Induced Psychotic with Hallucinations2,I I:nhalantTIneed Mood Disorder (292.89), (292.~~
TTrHalant-Induced Anxiety2~.89), .Related Disoxder Not Disorder ~ Inh.al.a Otherwise Specified (292.9), ni~lelirium$1), Opioid-Induced Opioid Intoxieati (29 Psychotic ~
Disorder with Deh>sionsi~I'd IntoxioatiG Delirium (292.$1), (292.11), Opioid-Induced Psychotic Disorderh~inations12), Opioid-Induced with Ha l (z9' Mood Disomder (292.84), ~ or Similfgrlacting Arylcyclohexylamine Phencyclidine Intoxication (292.89)x, P} or 1y Acting Arylcyclohexylamine Pherlaycliditx ~ Siwil Intoxication l7elirium.c' lidine r Similarly Acting (292.81), P'h a (1?~CP~
~
Arylcyclohexylamine orlisord~rh Delusions (292.11 Induced Psyc ' ), ~
Phencyclidine (PCP) tiArylcy~lolxylamine IndGtced Psychotic or Similarly , t Disorder with hallucinations)~ encycl~din(PCP) or Si.mil.arly (292.1, ~ Acting Axylcyclohexylamine r2.8A~), .yc~d~e (pCP) or Similarly Mood Disord' Ph Acting Arylcyclohexylarnine 'Disorder..89), Phencyclidine Induced Anx ~ (2~ (PCP) or Similarly Acting Arylcyclohexyl ~telated ier Not Otherwise Specified T)i (292.9), Sedative, 1le Intoxicatii (292.89) ITypnotic or ' Sedation Hypnotic or , , Anxiolytic Intoxication2'l~1), Sedal;ion. yp370'tiC Or Anxiolytic belirium (2 ~ ' Withdrawal Delirium (292.81), ir Anxr:olyti~ duced Persisting Sedation, Hypnc't ~ hementia (292.82), Sedation, i~rtic-lndu~edsyc.hotic Disorder Hypnotic or An . with Delusions D~CST()R: 117613k11 (292.11), Sedation, 'tic-Inducedsychotic Disordex with Hypnotic or An"
I~allucinations (292.12), ~otic lytic-Induced Maod Disorder Sedation, I ~ or Anxi (292.$4), Sedation, itic-Induced.~cietyDisorder (292.89), Hypnotic or An;' ' Other (or .
Unknown) Substance Intoxication9'139}, Ltnktxown) Substance-Traduced ( ~ Other (c Delirium (292,81), Dther Substance-aced Persisting Dementia (or Unloz ~~
(292.$2), Other (or atc-Inducedchotie Disorder with Delusions Unknown) Sub P;
(292.11), Uther (or ai4~In.de~cedlotic Disorder with Hallucinations Unlrnown) Subs P:
(292.12}, Other (or are-Inducedo~.i Disorder (292.84), Other Unknown) Subs, (or ~Tnla~awn) Substance-InducedtDisorder.$~)), ~ (29 Other (or Unlrnown.) Substance Disorder Not p,~fied Obsessive Compulsive Disorder Qtherwise (292.9' (300.3), Post-traumatica(309.81),eralized Anxiety Disorder Stress l:3iso~ I G (300.02), Anxiety Disorder Not ~cied (300.00).c>dy Dysmorphic Disorder Otherwise S (300.7), ' aleurasis).7), Samatization Disorder Hypocltondriasis (or (3C
Hypochondria I~
(300.81,), Undifferentiatedrrpisorder.81), Somatoform Disorder Somato ~~ (3( Not i Otherwise Specif ed .mt ExplosivD isorder (312.3A~), Kleptomania (300.81 ), Intei i (312.32), Pathological 2L), Pyroma(312.33), Trichotillomania Gambling (31 ' (312.39), and Impulse ~et~TOS Schizophrenia, Paranoid Type, Control Disoyl (312.3 {295.30), Schizophrenia,ec'295.10),zophrenia, Disorg ~ I Scl Catatonic Type, (295.20), Scliizaphrenia,ti;- d Type9(1), Schizophrenia, Residual Undifferei {29. Type (295.60), Schizophreniformr95.40), a ffective Disorder (295.70), Disord' ~ Schi .
I
Delusional Disorder sI~otlc ( 298.8), Shared Psychotic (297.1), Brief Dlsor Disorder (297.3}, Psychoticx4e to Medical Condii~ion with Delusio~.~.s Disoxd ~a Gene (293.81), psychotic ageneral al Condition with Hallucinations Disorder Due ti IVIe , , I
(293.82), Psychotic mvise d (298.9), Major Depression, Disorders Not t Specif Single Episode, Severe, without~tares , Major Depression, Recurrent, Psychotic~ (296.2:
Severe, without Psychotic2i.33), Disorder, Mixed, Severe, Features~I Bipola without Psychotic Features (296.63),IBorder, Severe, with psychotic Features I3i.po.l~ ~ Mix (295.64), 'Bipolar Di.sarder,ae, withoutychotic Features {296.43), Manic, Bipolar Disorder, Manic, Severe,o, f'eahn~es6.44), Bipolar Disorder, with Psych ( Depressed, Severe, without Psychotic~2'>.53), Disorder, Depressed, Severe, Faahwes~ Bipoh with Psychotic Features (296.54),rl7isorder~.89), Bipolar Disorder Not Bipol. ~ 1{2 ~UCS-fOir: il7613811 Otherwise Specified (296.80}, Persq' a Ity bisorde aranoid (301.0), Persanal.iiy Disorders, Schi~aid (301.20), Perso ~ IyDisorders, chizotypal (301,22), Personality Disorders, Antisocial (301.7), and P~ ~nality Disar s, Borderline (301.83}.
The term "a patient in uee neatmept" a used herein will refer to any subject or psychiatric patient who c ~r l0.tly has or m dEVelop any of the above syndromes or disorders, including a ' y ymdition or ' cider in which the subj eet spends an exeeasivE amount of time in a shl p ytate or tlnabl to maintain a satisfactory degree o:f wakefulness during a period of the ,~rhecn wake 1 ess is required or desired or has lrZ7S.
Paliperidone, including its ~paceutiaallyaeptable acid addition salts, pl enantiomeric forms and estersa iiministeredr the practise of the preseu,t may invention. Paliperidone is y the described in ~t'.lrS Patent 5,158,952.
well 1rno art and ' As rioted in US Patent 5,158'9.~, paliperldohas basic properties and, conseduently, this compound ~ averted erapeutically active noai-toxic may b, to i acid addition salt forms by : I lh acids, such. as, far example, treatsnen apprapriat inorganic acids, such as hydrohalic~ I' e.,~.ori.c, hydrobromic acid and the like, ' hydroc sulfuric acid, nitric acid, ~ and or organic acids, s'Llch as, for phosphoriq the .
lilt example, acetic, propanoic, c tic, ropanoic, 2-oxopropanaic, hydro 2 hydrox ethanedioic, propanedioic, ' (Z)-2-butenioic, ()3)-2-butenedioic, 2-butanedi i . . ;.
hydrd~cybnta~nedioic, 2,3-dihydrou1j~edioic,, ~ 2-h y-1,2,3 propanetricarboxylic, m.eth.atlestafotlic, ethanesulfonie,I nesulfonic,ethylbenzenesnlfonic, be 4 .
cyclohexanesulfamic, 2-hydroxybe~ ~" ,4-amino-2ydroxybenzoic arid the like acids.
~
Conversely the salt form can o a srd base form by treafioent with be co into the alkali. The term acid addition yd hereinaba also comprises the solvates which salt a such compounds are able to d :iid meant to be included within the form ar..j I solvates scope ofthe present invention.p Is of tes are e,g,, the hydrates, Exa ~ such sol alcoholates and the like.
~
Esters of Paliperidone are ~ i~ in are described in't1S Patent the art ai 5,254,556. P,sters ofpaliperidonecl~~ie 'd, decanoic acid, dndecarlia acid, i octanoi.c a pOCS1'OTt I 17613811 ketxadecauoic acid or hexadecanoici(palmiti; ). The currently preferred acester of paliperidone is paliperidone paImit i Paliperidarle may be formaltol withrmeutical e~ccipie>Gtts into p a variety of . .
dosage forms as described 5,158,92.~peridone will in one embodiment in US P ' of the present invention inan ysaform. Suitable oral dosage be provide oral forms d include but are not limitedlel .releaser dad release dosage forms.
to contra . a Currently preferred are tr;dad age forms_ Most preferred are once daily a relo extended release OROS oral fawas are11 larown in the art. Examples dosag whit of oral dosage forms of paliperidonerascribedn 20040092534, US 20050208132 . U
and US 20050232995.
p'or the practice of this dopaliperiionshould be delivered with a inv dosage form that will provide low nentrationvation (peak to trough) for the plasma c ~ patient receiving treatment to reducevdaykimes1emess andlor sleep disturbance.
exce ~ ' Low plasma concentration m~ans headore variation in plasma variati ' that i concentration (Cmax-G'inin.)h:s beennied. As illustrated in. Figure / Cm ' m '.1 a l.ow plasma concentration variation d by : ge form being tested (specifically is th d between day ~ and 7). The ~r'atioripla concentration from the intrados ~ ' maximum plasma concentrationax) linium plasma concentration (Cmin) (C I to the ~
when minimized reduces excessive a sIe yins and/or sleep disturbance.
rn one embodiment of the invention,ation ismconcentration from Cmax to the r ' :in Cmin p will be less than about ei~rably~ about 30 percent, morE preferably 35 percent, p~ les th~
h-om about 10 percent to ~t, preably from about 15 percent about 30 ~I most to about 25 percent. These aelated(C5ax-Cmin) I Cmax from the ranges are ~ a - administration o:f one to next.rofbly the dosing will be onto dosage form t t per ~Y. ~ ~
I
For the avoidance of doubt ', in adose'° o ~ "ir dose period" refers to the period between the initiation of dnlg rele ~ 1 y a dosa ° fo: . .from. its administration until the administration of the next dose of s ' usage f rm a dosixlg regiment.
Generally, this period will be the period from the a; ~ nistrati.otl of a dose to the administration of another dose, except where a doe;ag' ~: rln does fiat lease drug imanediately upon DOCSTOR; 117GL3811 adnunistrati.on. hi this case, the pe .a of delay of r ease of the drug will have to be considered. This adjustment shoul~b~ considered ia~~establishing Cmin.
Additionally, Figure 1 illust at s a flat plash curve. "Flat plas>ana curve"
means a plasma concentration curve that . ac ies and maim 'ns a substantially constant value after a defined period of time folio " y administrati of a dosage form according to the invention. A steady state wherein t ~e bsolute vain o,f Ctnax and Cmin are relatively canstan.t from day to day is achieve a .er about 6 d: s.
"C" means the concentratio o 'drug in bloo plasma, or serum, of a subject, generally expressed as mass per i ~ v lume, typica nanograms per milliliter.
For convenience, this concentration ma, b ~ referred to .. ein as "drug plasma concentration", "plasma drug cane atr ti.on" ar '~la a concentration". The plasma do-ug concentration at any time foil. ~ ~ ig drug admix stration is referenced as Ctime, as in C9h or C24h, etc. A maximum pla m concentratio obtained following administration of a dosage form obtained directly o the experim tai data without interpolation is rei'erted to as Cmax. A minimum a na concentra ' n obtained following administration of a dosage .fomn. ab i.i ed directly fr ~n experimental data without interpolation is referred Cmin II.
Persons of sI~ill in the a~~ wi 1 a predate the loud plasma drug concentrations obtained in individual subjects will ~ y due to inter atient variability izt the many parameters affecting drug absorpti , 'stribution, tabolism and. excretion. For this reason, unless otherwise indicated, h ~ t a drug pl , as caocentratian is listed, the value listed is the calculated mean value ~ 'd on values l~tained from a groups of subjects tested II.
Those of ordinary s1d11 will that paliperidone, in th appreci its salts, enantiomers, and esters, v~red known uses of risperidane.
can be ad for Far all th example paliperidone a 11 schixaphre~.schizoaffective disorders, can be used to i bipolar mania dr other diseasep ~ychosis,sive behavior, anxiety states in whi aggr or depression is evidenced (e.g. ith dementiapost traumatic stress psychosis associa syndrome, etc.).
As used herein the I;je t", refersanimal, preferably term "su to I a mammal, and.
most preferably a human,cey the (treatment, al~servation who has 1 object or a .
T)0(:S'f'OR: I t7611fl~1 experiment.
The term "therapeuticallya five >'used herein, means rimaurat'that alnaunt of active compound or g t that . a biological ar medicinal pharmaceutical : elicits response in h'mnan that is being rcer, medicaltor or other clinician, sought by a res ' wtuch includes alleviation of the ' or disordereing treated.
symptoms of the di Those of slcill in o.; diseases. easily determine the the treatmer cau effective amount of paliperidonefov the f the diseases listed to administer treatmenabove. In general it is contemplatedc ve amount1d be from about 0.01mg/kg that an eff ' w to abort 2 mglkg body weight. m t ofthe ~t invention, paliperidotte In one embo pres is administered in an toa subjecta day. The mg o:l'compaund oral dosage fo one delivered in such . atient from 0.25 to about 20 a dosage form to a may mg (e.g. 0.25 1 b rng, 0.5 mg, I mg, ',mg,.6 ig, $ mg, 9 mg, 10 mg, 2 mg, 3 mg, 4 m mg, 11 mg, I2 mg, 13 mg, 14 mg, ig, 1$ ~~ng, and 20 mg) per 15 mg, I6 mg, 1 sng, oral dosage form.
'~ ~ ~ ~ -DOCS'I'UK: 11761381 ExAlvr:PraF y Psliperidone Cspsul~ Shaped T'ablet~'r'rilayar 2 mg System A dosage form adapted, d and an osmotic drug delivory des shapE device was manufactured as ~ paliperidane325 g of polyethylene follows: 120 oxide with average molecular weight, d 2000 odium chloride, USl' of 2DD,0 g o were added to a fluid bed granulator~ ~der as prepared by dissolving bowl. Next a solution400 g of hydroxypropylmethyl ~ ed as ' g an average viscosity cellulose id 2910 of 5 cps in h '7,b00 g o.f water. a fluid >.nulated by spraying The dry rx~.aterial.s bed with 4,000 g of binder solution. Next,t on was i the granulatar to the wet gran dried an acceptable moisture content, and p ssing a 7>>nesh screw. Next, sized using b throu the granulation was transferred r and 'th 5 g of butylated to a b1a mixed hydroxytaluene as an antioxidant and 5 g of cid.
lubricated wi stearic Next, a second drug nt campositi~ was prepared as follows:
compa 2$0 g of paliperidone and 9165 a oxide verage molecular weight g of polyeth with of 200,000 were added to a fluid b wl.. . der solution was prepared bed granulato Next by a b dissolving 400 g of yl celluloseentified as 2910 having hydroxypropyl i an average viscosity of S cps . E dry were fluid bed granulated in 7,600 g of wet mat by ~
spraying with 4,000 i n. Next,t granulation was dried g ofbinder sox the in. the gtanlulator to an acceptablec >ateut, d using by passing through moister ~ and a 7-si mesh screen. Next, transferreda blender and mixed with the granulation S g of butylated hydroxytoluenexiant and,.ated with 50 g of stearic as an anti lubr acid.
Next, a push composition epared ows: fast, a binder solution W as fo was prepared. 15.6 leg i one identifiesas K29-32 having an average ofpolyvinylpyrr ~
molecular weight of l ed in ~ of water. Then, 24 kg 40,000 was dis 104.4 of sodium eh.l.oride and 1.2 sized Quadro Comil with a 21-mesh kg of ferric oxide using screen. Then, the screened d 88.44 olyethylene oxide {approximately material ~ kg of 7,000,000 molecular d to d ganulator bowl. The dry weight) were a fluid materials were fluidized ile 4G.2cinder solution was sprayed and mixed kg o from 3 ~
nozzles ants the powder.a ion was n the fluid-hed chamber The gran I dried to an DOC99y7R: 117617811 acceptable rnoistttre level. The coated l;ranules ware ~~ued using a Fluid Air mill wikh a 7-mesh screen. Tl~e granulation was transfeiTed to a t to tumbler, mixed with 1 S g of butylated hydroxytoluene and lubricated with 29A~ g lagnesium stearate.
Next, the paliperidone drug compositions fo fihe first and the second compartments and the push composition were pomp ~;ssed into trilayer tablets.
first, 50 mg of the paliperi.dan.e compartment one compositio was added to the die cavity and pre-compressed, then SO mg oftlxe paliperidone co paxtment two composition vsras added to the die cavity and pre-compressed, then 10 mg of the push campasition was added and the layers were pressed into a 3116" diem ~er longitudinal, deep concave, trilayer arrangement.
The trilayered arrangements vvene coated wi ~ a subcoat laminate. The wall forming composition comprised 70% bydroxyprapy pellulase identified as EF, having an.
average molecular weight of 80,000 and 30% ofpol 'nylpyrrolidone identified as T~29-32 having aJ.~. average molecular weight: of 40,000. 7 ne wall-forming composition was dissolved in auhydrous ethyl alcohol, to rnalce an 8°/ ~~olids solution. The wall~forming eompositiou was spxayed ante and aro~~nd the bilay ed arrangements in a pa~.~
water until approximately 20 mg of laminate was applied t each tablet.
The trilayered arrangements were coated with a semi-permeable wall. The wall farming campasitian campri.sed 994/° cellulose aceta ~ havin.g a 39.8%
acetyl content and 1%~pal.yethylen.e glycol comprising a 3.350 viscosi -average molecular weight.
The wall-forming composition was dissolv~;d in an aceto e:water (95:5 wt:wt) co solvent to make a 5% solids solution. The wall-forming coynp pition was sprayed ante and around the bilayered vrxangements in a pan ca;tter until ppp ximately 40 mg of membrane was , applied to each tablet.
Next, two 25 mil (0.6 mm) exit passageways yvere laser drilled through the senli-permeable wall to connect the drug layer with the ex eriox of the dosage systm. The residual solvent was removed by drying far 144 hau s at 45 °C and ~5%
humidity. After drilling, the osmotic systems were dried for 4 holes ~~ 45 °C to remove excess moisture.
"fhe dosage form produced by this manu,factt 'e was designed to deliver 2 mg of paliperidone iu an ascending delivery pattern from o drug-cantai.ning cores.
The firsi DOCaTOR; 117fi13f;11 core contained 1.2% paliperidone, 73.25% polyethylene oxide possessing a 200,000 molecular weight, 20% sodium chloride, USP, S% hydroxypropylmethyl cellulose having an average viscosity of 5 cps, 0.05°/a butylated liydrcyytoluene, and 0.5% stearic acid, The second. drug core contained 2.8"/o paliperidone, 91.65% polyethylene oxide possessing a 200,000 molecular weight, 5% liydrox3~ropylm.ethyl cellulose having an average viscosity of 5 cps, 0.05% butylated hydroxytoluene, and 0.5% stearic acid. The push corxsposition comprised 73.7% polyethyletle oxide comprising a 7,000,000 molecular weight, 20% sodi4un chloride, S% polyviv~lpyrrolidoae possessing an average molecular weight of 40,000, 1% ferric oxide, 0.05% hutylated hydroxytoluene, and 0.25% magnesium stearate. The semi permeable wall was comprised of 99%
cellulose acetate of 39.8% acetyl content and 1 % polyotllylen~ glycol. The dosage form comprised two passageways, 25 mils (0.6 mm) on the canter of'the drug side.
EXAMPLI~; 2 Paliperidone Capsule Shaped Tables, Trilayer 3 mg System A dosage form adapted, designed and shaped as an osmotic ding delivery device is manufactured as follows: 2.246 kg of paliperidone, $7.2 kg of polyethylene oxide with :average'molecular weight of200,000 and 2~. kg of sodium chloride, trip are added to a fluid bed ~raaulator bowl. Faliperidone amovat includes a 4% manufacturing excess to compensate for losses during processing. ~e~, a binder sol.utinn is prepared by dissolving 7.2 kg ofpalyvinylpyrrolidone identified as X29-32 having an average molecular weight of 40,000 in 52. $ kg of water. The dry materials are fluid bed granulated by spraying with SO kg ofbinder solution: Next, the wet granulation is dried in the ganulator to the acceptable moisture content. Then, the dried granulation is sized using a Flitid Air mill with a 7~mesh screen. The grapulation is transferred to a tote ttmzbler, mixed with 60 g of butylated hydroxytoluene and lubricated with 600 g stearia acid.
bOC&TOR; 117EtSBlI
Ne~ct, a second drug compartment composition is prepared as follows: 5.242 kg of paliperi.done, 0.06 kg ofyellow ferric oxide and 108. kg of polyethylene oxide with average molecular weight of 200,000 are added to a fluid bed granulator.bowl.
Paliperidone amount includes a 4°/a manufacturing excess to cori~pensate for losses duristg processing. Next, a binder solution is prepared by dissolving 7.2 kg of polyvinylpyrrohdone identified as K29-32 having an :average molecular weight of 40,000 in 52.8 kg of water. The dry materials are fluid bed ~;ranul.ated by spraying with 50 kg of binder solution. Next, the wet granulation is dyed in th.e granulator to the acceptable moisture content: Then, the dried granulation is sized using a lr laid A.ir mill with a 7-mesh screen. The granulation is transferred to a tote ~utnbler, mixed with 60 g of butylated hydroxytolvene and lubricated with 600 g s~keatic acid.
Next, a push composition is prepared as follows: first, a bidder solution is prepared. 30 lcg of polyvinylpyrrolidone identified as X2.9-32 having an average molecular weight of 4D,000 is dissolved in 200.8 kg of water. Then, 100 kg of sodium chloride and 5 kg of red ferric oxide are sized using a Quadro Comil with a 21-mesh screen. Then, the screened materials and 368.50 kg of. Polyethylene o~cide (approximately ?,000,000 molecular weight) are added to a fluid bed granulator bowl. The dry materials are fl,uidized arid mined while 192 kg ofbinde~ soluti~pn is sprayed tom 3 nozzles onto the powder. The granulation is dried in the fluid-laed chamber to an acceptable.moisture level. The coated yanules are sized using a >~luid Air mill with a ?mash screen. The granulation is~transferred to a tote tumbler, mixed with 240 g of butylated hydroxytoluene and lubricated with 1240 g stearic acid.
Ne~ct, the paliperidone drug compositions For the first and the second ' r corrrpartmettts attd the push composition are compressed into trilayer tablets. First, 30 mg of the paliperidone compartment one composition is added to the die cavity and pre-compressed, then 54 mg ofthe paliperidono compartment two composition is added to the dic cavity and pre-compressed, then 140~mg of the push composition is added and the layers are pressed into a 3116" diameter lou,gitudinal, deep concave, irilayer arrangement.
oocsrotr; mstzsvr The trilayered arrangements axe coated vUith a subcaat lami.n.ate. The wall forming composition comprises 95% hydroxyethylcellulose and 5% ofpolyethylene glycol comprising a 3.350 viscosity-average ro.r~lecular weight. The wall-forming composition is dissa.lved in water, to make an 6P/° solids solution.
The wall-forming composition is sprayed onto and around the bil~yerec~ arrangements in a pan caater until approximately 10 mg of lai:ainate is applied to each tablet.
The trilayered arrangements are coated with ~ semi-permeable wall. The wall forming composition comprises ~9~% cellulose ~cetata having a 39.8% acetyl content and 1% polyethylene glycol comprising a 3.350 viscosity-average molecular weight.
The wall-forming composition is dissolved in an ac~ton.e:water (95:5 wt:wt) co solvent to make a 5% solids solution. The wall-forming composition is sprayed onto and arovmd tlxe bilayered arrangements iaa a pan coater untillapproximately X45 mg of membrane is applied to each tablet.
Next, two 25 mil (0.64 rnrxi) Exit passageways are laser drilled through the semi-permeable wall to connect the drug layer with tlfe exterior ofthe dosage system. The residual solvent is removed by drying for 144 hours at d.S °C and ~5%
hmnidity followed I I
with approximately 1 hour at 45 °C to remove e~ces~ tlloisture.
The dosage farm produced by this rnanufl~ctur~ is designed to deliver 3 mg of paliperidone in an ascending delivery pattern from tv~a drug-containing cores.
Pnliperidone ~'apsnle Shaped Tablet, Tr.ilayor ~ mg System A dosage form adapted, designed and sllape~ as aroL osmotic drug delivery device is manufactured as follows: 6.64 kg o~paliperido~Ie, 8285 kg afpolyetloylene oxide with average molecular weight of 200,000 and 24 kg. of sodium chloride, ~(.TSP are added to a fluid bed granulator bowl. Paliperidane amaun~ includes a 2.5% manufacturing excess to compensate far losses during processing. N~ext,~a binder solution is prepared by dissolving 7.2 kg oCpolyvinylpyrrolidoue identified ~s 1C29-32 having an average molecular weighLt of 40,000 in 52. & kg of water.; The ~lry materials are fluid bed 16 ~
DOCSTOk: 1 L7613811 'I
granulated by spraying with 50 kg of binder solution. Next, the wet granulation is dried in the granulator to the acceptable moisttue content. Then, the dried granulation is sized using a Fluid Air mill with a.7-mesh. screen. The grapulation is transferred to a tote.. .
tumbler, mined with GO g of butylated hydroxytoluenw and lubricated with 600 g stearic acid.
Next, a second drug compartment composition is~prepared as follows: I5.50 leg of paliperidone, 0.01$ >~g ofblack iron oxide, and 98.20 kg ofpolyethylene oxide with average molecular weight of 200,OOU arE added to a ilttid bed granulator bowl.
Paliperidone amount includes a 2.5% manufacturing gxcess to compensate for losses during processing. Next, a binder soluti.an is prepared by dissolving 7.2 kg of polyvinylpyrrolidane identif ed as 1029-32 having an average molecular weight of 40,000 in 52.8 kg ofwatex. The dry materials are fluid bed gt~a,nulated by spraying with 50 kg of binder solution. Next, the wet granulation is dried in the granulator to the acceptable moisture cor»tent. Then, the dried granulation is sixec~ using a Fluid Air mill with a 7~
mesh screen. The granulation is transferred to a tote tumbler, mixed with 60 g of butylated hydroxytoluene and lubricated with G00 g sxearic acid.
Next, a push composition is prepared as follows: first, a binder solution is prepared. 30 ltg ofpolyvinylpyrrolidone idenfiihed as K29-32 having an average molecular weight of 40,000 is dissolved in 200.8 lcg of water. Then, 100 kg d:f sodium chloride and 5 kg ofred ferric oxide are sized using a.Quadro Comil with a 21-mesh screen. Then, the sc~~eened materials and 368.Sp kg o;f Polyethylene oxide (approximately 7,000,000 molecules weight) are added to a fluid bed granulator bowl. The dry materials are fluidized and mixed while 192 leg of binder solution is sprayed from 3 no:ccles onto the powder. The granulation is dried in the .fl.uid-bed chamber to an acceptable moisture level. The coated granules are sized using a Fluid Air mill with a 7-mesh screen. The granulation is transferred to a tote tumbler, mixed with 240 g o,f butylated hydroxytoluene and lubricated with 1200 g stearic acid.
Next, the paliperidone drug compositions for the first and the second compartments a~~.d the push composition are compressed into trilayer tablets.
First, 50 mg of the paliperidone compartment one composikion is added to the die cavity and pre-compressed, then 50 mg of the paliperidone compartment two composition is added fXICSTOR: i 17613811 to the die cavity and pre-compressed, then 100 mg of the push composition is added and the layers are pressed into a 3/16" diameter longitudi»al, deep concave, trilayer arrangement.
The trilayered arrangements are coated with a subcaat laminate. The wall forming composition comprises 95°~o hydroxyethylce;[lulose and 5%
ofpolyethylene glycol comprising a 3.35p viscosity-average molecuhr weight. The wall-forming composition is dissolved in water, to make an 8% sal'ids solution. The wall-forming composition is sprayed onto and around the bilayered arrangements in a pan.
canter until approximately 10 mg of laminate is applied. to each tyblet.
The trilayered arrangements ors coated with a semi-permeable wall. The wall forming composition comprises 99°,~° cellulose acetate having a 39,8% acetyl content and 1 % polyethylene glycol comprising a 3.350 viscosity-average molecular weight.
The wall-forming composition is dissolled in an acetone:water (95:5 wt:wt) ca solvent to make a 5% solids solution. The wall-forming cam.pas.itian is sprayed onto and around the bilayered arrangements in a pan coater until approximately 45 mg of membrane is applied to each tablet.
Next, two 2S mil (0.64 mm) exit passageways are laser drilled through the semi-permeable wall to connect the drug layer with the exterior of the dosage system. The residual solvent is removed by drying for 144 hoiu's at 45 °C axed 45%
humidity followed with apprQxinnate 1 hour at 4S °C to remove e~ccess moisture.
The dosage form produced bn ilus rnaaulacturs is designed io deliver 9 mg of paliperidone in an ascending delivery pattern from two driGg-contnitung cores.
3~OCS'fOR: I 17G138S1 rierermi~nation of )Plasma Parofile of ~alipe~idone OROS farmttlation Dosage and Administration RISPER1DAL~ (risperidone iR) brand risperi.don.e vas administered to subjects (in these examples the subjects are human patients). 'fhe initial dose of risperidone was 2 mg/day and titrated to 4mglday an Day 2. Because tho bioav,ailability of ER OROS
paliperidone is approximately 30% that of an oral solution ofpali,~erid.one, l2mg ER OR4S
paliperidone dose was selected to be administered as!an equivalent dose with.
respect to plasma levels to 4mg 1R risperidone. The >3R OROS ~aliperidone was provided as 2mg-tablets made substantially as described in Example 1.
Subjects in each group were given a once-daily oral dose, consisting of six (6) 2mg capsules, every morning daring the washout anc~ double-blind treatment periods.
Shady medication was administered sitting in att upright position with 200m1r, of water immediately after a standardized breakfast eaten. between approximately 8:00 a.m. and l0:0o a.m.
Study Evaluations Subjects were required to complete a washou~ period prior to participation in the study. Subjects who successfully completed the washout period atzd continued to meet eligibility criteria were randomly assigned. in equal n~xmber to one of three treatment groups (tbe results of two the treatment groups are provided in this example);
(1.) Paliperidon.e OROS or (2) risperidone immediate rel' ase. During the double-blind treatinent please (days 1 td 6) , sittdy medication was~administored after a standard breakfast. AlI meals during the study, including the vjr~ashout anal treatment periods, were standardized, consisting of a normal sodium diet with approximately 2,500 Kcal per 24 hours. The subject's total fluid intake was monitored and was not to exceed 3,000 mL
per 24 hours. Subjects were to have no more 'than 3 an.ethyIxanthin-containing beverages(e.g. cola, tea coffee) daily. Soft drinks w~re permitted as long as they did not ~ocs~roa: ~ i7s»su contain quinine ar caffeine and did nol: increase the permitted total daily calories allowance. Other foods including chocolate, grapefrpit, grapefn>,it juice, Seville oranges and quinine-containing beverages were not allowed. Strenuous physical activity was not permitted during the study.
Pharmaculdnetic Evaluations At time points during the double-blind tree 'ent period. until the end of the study on Day 7, blood samples were obtained for measv ent of risperidone, paliperidone and active moiety concentrations in plasma. In each treafiient group, a venous blood sample of S nnl, was drawn to obtain about 2 tn 3mL o:f plasrj~a. The Collection schedule was as follows:
On day 1, immediately before dosing at~d at ~, 2, 3, A., 6, 8, 12, 18, a;nd 22 hours postdose:
W Aay 2 through Day ~, immediately befor dosing and at 2 and 22 hours postdase;
i On Day 6, imynediately before dosing and at ~, 2, 3, 4, b, 8, 12, 18, 22, and hours postdase (on Day 7).
Plasma concentrations of risperidone and pal~perid~one were determined by using a validated liquid cvromatography coupled to mass s~~yoctrometry/mass spectrometry, method.
For the subjects rvho received IR risperidone,;the active moiety concentrations were calculated as the sum of the risperidane and paliperidone concentrations.
L'1f)LS7QFt: l 17fi1381!
. - Sleep >Stu~dy i Purpose: Nighttime sleep disturbance and daytime drowsiness are common in patients witli schizophrenia, and can be a significant concern. far patients tlzai is net always effectively addressed with pharmacolqgic treatment.'faliperidone exte~~ded-release tablet (paliperidone IJR) is an investigational. psychotropicl~tipsychotic agent, with once-daily dasittg, that bas been shown to be efficacious and waI'lll-tolerated in 6-week Trials of patients with schi~ophreniat'3. Effects ofpaliperidon~ ER on changes in. sleep architechtre (Dataset 1) were studied in patie~~.ts with schizophrenia~.relatad insomnia, and the clinical importance of these findings was further assessed by patient-rated changes in quality of sleep and daytime drowsiness (Dataset 2) in patients with schizophrenia.
I
Methods: Data were collected in multicenter, doabh-blind, randomized and placebo-cantroll.ed studies in patients with either stable (Data~et 1) or acute (Dataset 2) schizophrenia. Tn I7ataset 1 (n~2) paliperidone ER ~mg ar placebo were administered daily for 2 weeks. Polysomnography (PSG) variables were assessed afi baseline and endpoint. Other sleep measures included Leeds SleeR Evaluation Questiannsire (LSE.
Dataset 2 (n=1326) was a post-hoc analysis of pooled data .from three, G-week studies'-' with paliperidone ER 3mg, 6mg, 9mg, l2mg, 1 Smg, nor placebo daily. The paliperidone ER capsules were prepared as described in Exatr3ple yu~d 3 above. Patients dosed with.
5mg were provided with two 3mg tablets. Patients dosed with l2~mg were provided with one 3mg and one 9mg tablet, Patients dosed with lStirg were provided a 9mg and two i 3mg tablets. Subjects completed Visual Analogue Sale (VAS) assessments of sleep q~.valiiy ('How well have you slept in the past 7 night?') and daytime drowsiness ('How often have you felt drowsy in the past 7 days?').
I
Results: Dataset 1 analysis set {n~36) consisted of 6'~4/o male, mean~SD
age=32.2yt7.3, baseline meantSD PANSS total score=62.9111.2, mean PSG measured latency to persistent sleep of S8.7~45.8 minutes, sleep onset lat~ucy of 49.~~41 _1 minwtes, at~d a severity o.f insomnia confirmed by a baseline mean deep Ef&ciency Index (SEA
of UOCS'I'OH: t17613fl11 7b~:13.4%. '.Treatment with paliperidone ER resulted rn clinically robust and statistically significant improvements in. sleep, including decrsas~s in latency to persistent sleep (41.9-X23.7 minutes) and sleep onset latency (35.92 .6 minutes). SEI was improved (77.515.6%), total sleep time increased (370.474.3 minutes), Stage 11 sleep duration increased (219.3152.5 minutes), and REM sleep dur Lion increased ($O.1f24.6 minutes).
Pali.peridone ER was witliout significant effects~on slew wave sleep. No statistically significant difference was observed, for any ehatlge ir+ LSEQ scare. The clinical relevance of these findings was supported by Dataset 2 (TTT set: n=1.306, 62%
male, mean~SD age~38.1y~10.9, baseline meaWSD pAN 'S total score=93.5111.8). A11 S
doses ofpaliperidane ER provided s.ignficantly grea cr improvements in quality afsleep compared with placelao, as rated by VAS assessment (mean~SD baselinelchange at endpoint: palipetidone ER 3mg=56.4~28.819.Ot3~.:5; paliperidone ER
fimg=53.5~30.3/11.1~33.7; paliperidone ER 9ixig=SG.5~28.7I11.4~33.0;
paliperidone ER
I
l2mg=55.7~28.0/9.7~33.7; paliperidone ER 1 Smg=53.2~29.1111.3a:33.2;
placebo=52.4~29.310.6t35,9 [p~0.U5]). No signific it daytime drowsiness was associated with paliperidone ER t~~eatment (mea,n~Sl~ baseline/change at ettdpaint:
paliperidone LR 3mg=29.4t26.6/-2.928.1; palipera~an,e ER 6~.ng=28.325.1/-0.927.9;
paliperidone ER 9mg=31.Sf27.3/-~..1~32.4; palaperi lone ER l2mg=32.526.81 2.9131.0; pal.i.peridane ER l5mg=3$.5130.31-3at3 .5; placebo=32.3127.3!-3.030.0 ~p~a.os]).
i Conclusions: '1~hese studies suggest that paliper~dan~ ER treahn.ent resulted.
in improvements in sleep architecture and sleep continu'ty and. patient-rated sleep quality without producing or e~cacerbating the daytime draw mess that is typically open associated with therapies effective for the treattr~ent f insomnia.
References 1. Marder S, et al. Neurapsychapharmc~coi 2005; 3p: S2Q0 2. Kane 1, et al. Neuropsychopharmucol 2QQ5; 30: 5191~I-2 3. Davidson M, et al. Schiaophr Res 2006; 81: S43 1?OCST072: 17 761351
Claims (17)
1. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
2. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
3. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
4.~The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
5. ~The use of any one of claims 1 to 4 wherein the treatment is for excessive daytime sleepiness.
6. The use of any one of claims 1 to 4 wherein the treatment is for a sleep disturbance.
7. The case of any one of claims 1 to 4 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar -diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
8. The use of any one of claims 1 to 4 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from tile group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
9. The use of any one of, claims 1 to 4 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II disorder.
10. The use of any one of claims 1 to 4 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation;
Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation;
Mental Retardation Severity Unspecified ; Autistic Disorders; Rett's Disorder;
Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-Induced Persisting Dementia; Alcohol-lnduced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamine ar Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced psychotic disorder with Delusions;
Hallucinogen-Induced Mood Disorder; Hallucinogen-Induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) ar Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acing Arylcyclohexylamine Mood Disorder; Phencyclidine [PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified; Sedative, Hypnotic ar Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological.
Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severed with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation;
Mental Retardation Severity Unspecified ; Autistic Disorders; Rett's Disorder;
Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-Induced Persisting Dementia; Alcohol-lnduced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamine ar Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced psychotic disorder with Delusions;
Hallucinogen-Induced Mood Disorder; Hallucinogen-Induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) ar Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acing Arylcyclohexylamine Mood Disorder; Phencyclidine [PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified; Sedative, Hypnotic ar Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological.
Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severed with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
11. The use of claim 6 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type;
Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Brief Psychotic Disorder;
Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations;
Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severed with Psychotic Features;
Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features; Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid;
Personality Disorders, Schizotypal; Personality Disorders, Antisocial; and Personality Disorders, Borderline.
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type;
Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Brief Psychotic Disorder;
Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations;
Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severed with Psychotic Features;
Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features; Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid;
Personality Disorders, Schizotypal; Personality Disorders, Antisocial; and Personality Disorders, Borderline.
12. The use of any one of claims 1 to 4 wherein the how plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about percent.
13. The use of any one of claims 1 to 4 wherein the how plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
14. The use of any one of claims 1 to 4 wherein the low plasma concentration variation comprises a change in plasma concentration. (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
15. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
16. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma, concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
17. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid. Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with.
Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
l8. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition. with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorders, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with, Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and personality Disorders, Borderline.
19. The use of any one of claims 15 to 18 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
20. ~The use of any one of claims 15 to 18 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 1.0 percent to about 30 percent.
21. The use of any one of claims 15 to 18 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
22. ~The use of any one of claims 15 to 18 wherein the treatment is for excessive daytime sleepiness.
23. ~The use of any one of claims 15 to 18 wherein the treatment is for a sleep disturbance.
24. ~The use as claimed in any one of claims 1 to 23, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
25. ~The use as claimed in any one of claims 1 to 23, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
26. ~The use as claimed in claim 25, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
27. ~The use as claimed in any one of claims 1 to 26, wherein the pharmaceutical composition comprises an oral dosage form.
28. The use as claimed in claim 27, wherein the oral dosage form is an extended release dosage form.
29. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
30. The use of claim 29 wherein the treatment is for excessive daytime sleepiness.
31. The use of claim 29 wherein the treatment is for a sleep disturbance.
32. The use of claim 29 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
33. The use of claim 29 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
34. The use of claim 29 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II
disorder.
35. The use of claim 29 wherein the psychiatric patient has a mental disorder or mental illness selected from the goup consisting of Mild Mental Retardation; Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ; Autistic Disorders; Rett's Disorder;
Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamine or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions;
Hallucinogen-Induced Mood Disorder; Hallucinogen-Induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic, Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified; Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Auxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
36. The use of claim 31 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
37. The use of claim 29 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
38. The use of claim 29 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
39. The use of claim 29 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
40. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
41. The use of claim 40 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
42. The use of claim 40 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
43. ~The use of claim 40 wherein the low plasma concentration variation comprises a change in plasma. concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
44. ~The use of claim 40 wherein the treatment is far excessive daytime sleepiness.
45. ~The use of claim 40 wherein the treatment is for a sleep disturbance.
46. ~The use as claimed in any one of claims 29 to 45, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
47. ~The use as claimed in. any one of claims 29 to 45, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
48. ~The use as claimed in claim 47, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
49. ~The use as claimed in any one of claims 29 to 48, wherein the pharmaceutical composition comprises an oral dosage form.
50. ~The use as claimed in claim 49, wherein the oral dosage form is an extended release dosage form.
51. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
52. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition. providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
53. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
54. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
55. The use of any one of claims 51 to 54 wherein the treatment is for excessive daytime sleepiness.
56. The use of any one of claims 51 to 54 wherein the treatment is for a sleep disturbance.
57. The use of any one of claims 51 to 54 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
58. The use of any one of claims 51 to 54 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
59. The use of any one of claims 51 to 54 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II disorder.
60, The use of any one of claims 51 to 54 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation;
Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation;
Mental Retardation Severity Unspecified; Autistic Disorders; Rett's Disorder, Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-reduced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamino or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions;
Hallucinogen-Induced Mood Disorder; Hallucinogen-Induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamino Related Disorder Not Otherwise Specified; Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
61. The use of claim 56 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severs, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
62. ~The use of any one of claims 51 to 54 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
63. ~The use of any one of claims 51 to 54 wherein the low plasma concentration variation comprises a change in plasma concentration. (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
64. ~The use of any one of claims 51 to 54 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
65. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Mayor Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
65. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected, from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
67. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Magic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
68. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type., Schizophrenia, Disorganized; Schizophrenia, Catatonic lope; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder hue to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
69. The use of any one of claims 65 to 68 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
70. The use of any one of claims 65 to 68 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
71. The use of any one of claims 65 to 68 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
72. The use of any one of claims 65 to 68 wherein the treatment is for excessive daytime sleepiness.
73. The use of any one of claims 65 to 68 wherein the treatment is for a sleep disturbance.
74. The use as claimed in any one of claims 51 to 73, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
75. The use as claimed in any one of claims 51 to 73, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
76. The use as claimed in claim 75, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
77. The use as claimed in any one of claims 51 to 76, wherein the pharmaceutical composition comprises an oral dosage form.
78. The use as claimed in claim 77, wherein the oral dosage form is an extended release dosage form.
79. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carries, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
80. The use of claim 79 wherein the ireatmerat is fox excessive daytime sleepiness.
81. The use of claim 79 wherein the treatment is for a sleep disturbance.
82. The use of claim 79 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
83. The use of claim 79 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
84. The use of claim 79 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II
disorder.
85. The use of claim 79 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation.;
Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ; Autistic Disorders; Rett's Disorder;
Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescentt Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamine or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions;
Hallucinogen, Induced Mood Disorder; Hallucinogen-induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-reduced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine [PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified; Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder-.--.-with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe. without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
86. The use of claim 81 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
87. The use of claim 79 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent, 88. The use of claim 79 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
89. The use of claim 79 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
90. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
91. The use of claim 90 wherein the low plasma concentration variation.
comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
92. The use of claim 90 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
93. The use of claim 90 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
94. The use of claim 90 wherein the treatment is for excessive daytime sleepiness.
95. The use of claim 90 wherein the treatment is for a sleep disturbance.
96. The use as claimed in any one of claims 79 to 95, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
97. The use as claimed in any one of claims 79 to 95, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
98. The use as claimed in claim 97, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
99. The use as claimed in any one of claims 79 to 98, wherein the pharmaceutical composition comprises an oral dosage form.
100. The use as claimed in claim 99, wherein the oral dosage form is an extended release dosage form.
101. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
102. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in creed thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
103. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
104. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for tho treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
105. The pharmaceutical composition of any one of claims 101 to 104 wherein the treatment is for excessive daytime sleepiness.
106. The pharmaceutical composition of any one of claims 101 to 104 wherein the treatment is for a sleep disturbance.
107, The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
108. The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
109. The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II disorder.
110. The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation; Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ;
Autistic Disorders; Rett's Disorder; Childhood Disintegrative Disorders;
Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type; Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type; Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type; Attention-Deficit/Hyperactivity Disorder NOS;
Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder;
Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type;
Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder; Tic Disorder NOS; Alcohol Intoxication Delirium;
Alcohol Withdrawal Delirium; Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication;
Amphetamine ar Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional;
Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations;
Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium;
Hallucinoben-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Mood Disorder;
Hallucinogen-Induced Anxiety Disorder; Hallucinogen-Related Disorder Not Otherwise Specified;
Inhalant Intoxication; Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations); Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise-Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions;
Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations;
Opioid-Inducal Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified;
Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium; Sedation, Hypnotic or Anxiolytic Withdrawal Delirium;
Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations; Sedation, Hypnotic ar Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication; Other, or Unknown, Substance-Induced Delirium;
Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder;
Anxiety Disorder Not Otherwise Specified; Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis; Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania; Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
111. The pharmaceutical composition of claim 106 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized;
Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise; Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and. Personality Disorders, Borderline.
112. The pharmaceutical composition of any one of claims 101 to 104 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
113. The pharmaceutical composition of any one of claims 101 to 104 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
114. The pharmaceutical composition of any one of claims 101 to 104 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
115. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features; ..
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
116. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
117. A pharmaceutical composition comprising a therapeutically effective amount of as enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual. Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief psychotic Disorder; Shared Psychotic Disorder;
psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
118. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
119. The pharmaceutical composition of any one of claims 115S to 118 wherein the l.aw plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
120. The pharmaceutical composition of any one of claims 115 to 118 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
121. The pharmaceutical composition of any one of claims 115 to 118 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
122. The pharmaceutical composition of any one of claims 115 to 118 wherein the treatment is for excessive daytime sleepiness.
123. The pharmaceutical composition of any one of claims 115 to 118 wherein the treatment is for a sleep disturbance.
124. The pharmaceutical composition as claimed in any one of claims 101 to 123, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
125. The pharmaceutical composition as claimed in any one of claims 101 to 123, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
126. The pharmaceutical composition as claimed in claim 125, wherein the therapeutically effective mount is from about 3 mg to about 12 mg.
127. The pharmaceutical composition as claimed in any one of claims 101 to 126, wherein the pharmaceutical composition comprises an oral dosage form.
128. The pharmaceutical composition as claimed in claim 127, wherein the oral dosage form is an extended release dosage form.
129. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
130. The pharmaceutical composition of claim 129 wherein the treatment is for excessive daytime sleepiness.
131. The pharmaceutical composition of claim 129 wherein the treatment is for a sleep disturbance.
132. The pharmaceutical composition of claim 129 wherein the psychiatric patient lies a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
133. The pharmaceutical composition of claim 129 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
134. The pharmaceutical composition of claim 129 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I
disorder and Bipolar II disorder.
135. The pharmaceutical composition of claim 129 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation; Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ; Autistic Disorders;
Rett's Disorder; Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type; Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type; Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type; Attention/Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder; Tic Disorder NOS; Alcohol Intoxication Delirium;
Alcohol Withdrawal Delirium; Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication;
Amphetamine or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional;
Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations;
Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium;
Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Mood Disorder;
Hallucinogen-Induced Anxiety Disorder; Hallucinogen-Related Disorder Not Otherwise Specified;
Inhalant Intoxication; Inhalant Intoxication Delirium; Inhalant-Induced.
Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations); Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions;
Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations;
Opioid-Induced Mood Disorder; Phencyclidine (PCP) ar Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delixium; Phencyclidine (PCp) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (pCp) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified;
Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic-Intoxication Delirium; Sedation, Hypnotic or Anxiolytic Withdrawal Delirium;
Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations; Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic ar Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication; other, or Unknown, Substance-Induced Delirium;
Other, or Unknown, Substance-Induced persisting Dementia; Other, or Unknown, Substance-Induced psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder;
Anxiety Disorder Not Otherwise Specified; Body Dysmorphic Disorder; Hypochondriasis, or hypochondriacal Neurosis; Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania; Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
136. The pharmaceutical composition of claim 131 wherein psychiatric patient has a mental disorder or mental illness selected from the soup consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized;
Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severs, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar. Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
137. The pharmaceutical composition of claim 129 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
138. The pharmaceutical composition of claim 129 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 14 percent to about 30 percent.
139. The pharmaceutical composition of claim 129 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
140. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
141. The pharmaceutical composition of claim 140 wherein the low plasma concentration variation comprises a change in plasma concentration. (Cmax-Cmin/Cmax) of less than about 30 percent.
142. The pharmaceutical composition of claim 140 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
143. The pharmaceutical composition of claim 140 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
144. The pharmaceutical composition of claim 140 wherein the treatment is for excessive daytime sleepiness.
145. The pharmaceutical composition of claim 140 wherein the treatment is for a sleep disturbance, 146. The pharmaceutical composition as claimed in any one of claims 129 to 145, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
147. The pharmaceutical composition as claimed in any one of claims 129 to 145, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
148. The pharmaceutical composition as claimed in claim 147, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
149. The pharmaceutical composition as claimed in any one of claims 129 to 148, wherein the pharmaceutical composition comprises an oral dosage form.
150. The pharmaceutical composition as claimed in claim 149, wherein the oral dosage form is an extended release dosage form, 151. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the sympthoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
152. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
153. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
154. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
155. The use of any one of claims 151 to 154 wherein the treatment is for excessive daytime sleepiness.
156. The use of any one of claims 151 to 154 wherein the treatment is for a sleep disturbance.
157. The use of any one of claims 151 to 154 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
158. The use of any one of claims 151 to 154 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
159. The use of any one of claims 151 to 154 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
160. The use as claimed in any one of claims 151 to 159, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
161. The use as claimed in any one of claims 151 to 159, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
162. The use as claimed in claim 161, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
163. The use as claimed in any one of claims 151 to 162, wherein the pharmaceutical composition comprises an oral dosage form.
164. The use as claimed in claim 163, Wherein the oral dosage form is an extended release dosage form.
165. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
166. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
167. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
168. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
169. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
170. The use of any one of claims 166 to l69 wherein the treatment is for excessive daytime sleepiness.
171. The use of any one of claims 166 to 169 wherein the treatment is for a sleep disturbance.
172. The use of any one of claims 166 to 169 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
173. The use of any one of claims 166 to 169 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
174. The use of any one of claims 166 to 169 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
175. The use as claimed in any one of claims 166 to 174, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
176. The use as claimed in any one of claims 166 to 174, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
177. The use as claimed in claim 176, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
178. The use as claimed in any one of claims 166 to 177, wherein the pharmaceutical composition comprises an oral dosage form.
179. The use as claimed in claim 178, wherein the oral dosage form is an extended release dosage form.
180. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein.
the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
181. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
182. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
183. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
184. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
185. The use of any one of claims 181 to 184 wherein the treatment is for excessive daytime sleepiness.
186. The use of any one of claims 181 to 184 wherein the treatment is for a sleep disturbance.
187, The use of any one of claims 181 to 184 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
188. The use of any one of claims 181 to 184 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
189. The use of any one of claims 181 to 184 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
190. The use as claimed in any one of claims 181 to 189, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
191. The use as claimed in any one of claims 181 to 189, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
192. The use as claimed in claim 191, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
193. The use as claimed in any one of claims 181 to 192, wherein the pharmaceutical composition comprises an oral dosage form.
194. The use as claimed in claim 193, wherein the oral dosage form is an extended release dosage form.
195. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
195. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
197. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
198. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
199. The use of any one of claims 195 to 198 wherein the treatment is for excessive daytime sleepiness.
200. The use of any one of claims 196 to 198 wherein the treatment is for a sleep disturbance.
201. The use of any one of claims 196 to 198 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
202. The use of any one of claims 196 to 198 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
203. The use of any one of claims 19G to 198 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
204. The use as claimed in any one of claims 196 to 203, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
205. The use as claimed in any one of claims 196 to 203, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
206. The use as claimed in claim 205, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
207. The use as claimed in any one of claims 196 to 206, wherein the pharmaceutical.
composition comprises an oral dosage form.
208. The use as claimed in claim 207, wherein the oral dosage form is an extended release dosage form.
209. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
210. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
211. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
212. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
213. The use of any one of claims 209 to 212 wherein the treatment is for excessive daytime sleepiness.
214. The use of any one of claims 209 to 212 wherein the treatment is for a sleep disturbance.
215. The use of any one of claims 209 to 212 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
216. The use of. my one of claims 209 to 212 wherein the low plasma concentration variation. comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
217. The use of an.y one of claims 209 to 212 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
218. The use as claimed in any one of claims 209 to 217, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
219. The use as claimed in any one of claims 209 to 217, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
220. The use as claimed in claim 219, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
221. The use as claimed in any one of claims 209 to 220, wherein the pharmaceutical composition comprises an oral dosage form.
222. The use as claimed in claim 221, wherein the oral dosage form is an extended release dosage form.
223. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
224. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient 1n need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
225. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament far improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
226. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition ,providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
227. The use o:f a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
228. The use of any one of claims 224 to 227 wherein the treatment is for excessive daytime sleepiness.
229. The use of any one of claims 224 to 227 wherein the treatment is for a sleep disturbance.
230. The use of any one of claims 224 to 727 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
231. The use of any one of claims 224 to 227 wherein the low plasma concentration.
variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
232. The me of any one of claims 224 to 227 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
233. The use as claimed in any one of claims 224 to 232, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
234. The use as claimed in any one of claims 224 to 232, wherein the therapeutically effective amount is from about 4.25 mg to about 20 mg.
235. The use as claimed in claim 234, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
236. The use as claimed in any one of claims 224 to 235, wherein the pharmaceutical composition comprises an oral dosage form.
237. The use as claimed in claim 236, wherein the oral dosage form is an extended release dosage form.
238. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
239. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
240. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
241. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament far improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
242. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
243. The use of any one of claims 239 to 242 wherein the treatment is for excessive daytime sleepiness.
244. The use of any one of claims 239 to 242 wherein the treatment is for a sleep disturbance.
245. The use of any one of claims 239 to 242 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
246. The use of any one of claims 239 to 242 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
247. The use of any one of claims 239 to 242 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
248. The use as claimed in any one of claims 239 to 247, wherein the therapeutically affective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
249. The use as claimed in any one of claims 239 to 247, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
250. The use as claimed in claim 249, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
251. The use as claimed in any one of claims 239 to 250, wherein the pharmaceutical composition comprises an oral dosage form.
252. The use as claimed in claim 251, wherein the oral dosage form is an extended release dosage form.
253. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
254. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
255. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
256. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof wherein the symptoms are selected from the group consisting or sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
257. The use of any one of claims 254 to 256 wherein the treatment is for excessive daytime sleepiness.
258. The use of any one of claims 2S4 to 256 wherein the treatment is for a sleep disturbance.
259. The use of any one of claims 254 to 256 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
260. The use of any one of claims 254 to 256 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
261. The use of any one of claims 254 to 256 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
262. The use as claimed in any one of claims 254 to 261, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
263. The use as claimed in any one of claims 254 to 261, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
264. The use as claimed in claim 263, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
265. The use as claimed in any one of claims 254 to 264, wherein the pharmaceutical composition comprises an oral dosage form.
266. The use as claimed in claim 265, wherein the oral dosage form is an extended release dosage form.
267. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
268. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
269. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
270. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected, from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
271. The pharmaceutical composition of any one of claims 267 to 270 wherein the treatment is for excessive daytime sleepiness.
272. The pharmaceutical composition of any one of claims 267 to 270 wherein the treatment is for a sleep disturbance.
273. The pharmaceutical composition of any one of claims 267 to 270 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
274. The pharmaceutical composition of any one of claims 267 to 270 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
275. The pharmaceutical composition of any one of claims 267 to 270 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
276. The pharmaceutical composition as claimed in any one of claims 267 to 275, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
277. The pharmaceutical composition as claimed in any one of claims 267 to 275, wherein the therapeutically effective amount is from about 0.25 mg to about 20 m.g.
278. The pharmaceutical composition as claimed in claim 277, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
279. The pharmaceutical composition as claimed in any one of claims 267 to 278, wherein the pharmaceutical composition comprises an oral dosage form.
280. The pharmaceutical composition as claimed in claim 279, wherein the oral dosage form is an extended release dosage form.
281. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
282. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
283. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
284. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
285. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively law plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
286. The pharmaceutical composition of any one of claims 282 to 285 wherein the treatment is for excessive daytime sleepiness.
287. The pharmaceutical composition of any one of claims 282 to 285 wherein the treatment is for a sleep disturbance.
288. The pharmaceutical composition of any one of claims 282 to 285 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
289. The pharmaceutical composition of any one of claims 282 to 285 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 1.0 percent to about 30 percent.
290. The pharmaceutical composition of any one of claims 282 to 285 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
291. The pharmaceutical composition as claimed in any one of claims 282 to 290, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
292. The pharmaceutical composition as claimed in any one of claims 282 to 290, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
293. The pharmaceutical composition as claimed in claim 292, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
294. The pharmaceutical composition as claimed in any one of claims 282 to 293, wherein the pharmaceutical composition comprises an oral dosage form.
295. The pharmaceutical composition as claimed in claim 294, wherein the oral dosage form is an extended release dosage form.
296. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
297. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
298. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
299. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
300. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
301. The pharmaceutical composition of any one of claims 297 to 300 wherein the treatment is for excessive daytime sleepiness.
302. The pharmaceutical composition of any one of claims 297 to 300 wherein the treatment is for a sleep disturbance.
303. The pharmaceutical composition of any one of claims 297 to 300 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
304. The pharmaceutical composition of any one of claims 297 to 300 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
305. The pharmaceutical composition of any one of claims 297 to 300 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 1,5 percent to about 25 percent.
306. The pharmaceutical composition as claimed in any one of claims 297 to 305, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
307. The pharmaceutical composition as claimed in any one of claims 297 to 305, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
308. The pharmaceutical composition as claimed in claim 307, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
309. The pharmaceutical composition as claimed in any one of claims 297 to 308, wherein the pharmaceutical composition comprises an oral dosage form.
310. The pharmaceutical composition as claimed in claim 309, wherein the oral dosage form is an extended release dosage form.
311. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration. variation of paliperidone to the psychiatric patient in need of treatment.
312. A pharmaceutical. composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
313. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
314. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
315. The pharmaceutical composition of any one of claims 312 to 314 wherein the treatment is for excessive daytime sleepiness.
316. The pharmaceutical composition of any one of claims 312 to 314 wherein the treatment is for a sleep disturbance.
317. The pharmaceutical composition of any one of claims 312 to 314 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
318. The pharmaceutical composition of any one of claims 312 to 314 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
319. The pharmaceutical composition of any one of claims 312 to 314 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
320. The pharmaceutical composition as claimed in any one of claims 312 to 319, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
321. The pharmaceutical composition as claimed in any one of claims 312 to 319, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
322. The pharmaceutical composition as claimed in claim 321, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
323. The pharmaceutical composition as claimed in any one of claims 312 to 322, wherein the pharmaceutical composition comprises an oral dosage form.
324. The pharmaceutical composition as claimed in claim 323, wherein the oral dosage form is an extended release dosage form.
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with.
Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
l8. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition. with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorders, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with, Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and personality Disorders, Borderline.
19. The use of any one of claims 15 to 18 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
20. ~The use of any one of claims 15 to 18 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 1.0 percent to about 30 percent.
21. The use of any one of claims 15 to 18 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
22. ~The use of any one of claims 15 to 18 wherein the treatment is for excessive daytime sleepiness.
23. ~The use of any one of claims 15 to 18 wherein the treatment is for a sleep disturbance.
24. ~The use as claimed in any one of claims 1 to 23, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
25. ~The use as claimed in any one of claims 1 to 23, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
26. ~The use as claimed in claim 25, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
27. ~The use as claimed in any one of claims 1 to 26, wherein the pharmaceutical composition comprises an oral dosage form.
28. The use as claimed in claim 27, wherein the oral dosage form is an extended release dosage form.
29. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
30. The use of claim 29 wherein the treatment is for excessive daytime sleepiness.
31. The use of claim 29 wherein the treatment is for a sleep disturbance.
32. The use of claim 29 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
33. The use of claim 29 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
34. The use of claim 29 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II
disorder.
35. The use of claim 29 wherein the psychiatric patient has a mental disorder or mental illness selected from the goup consisting of Mild Mental Retardation; Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ; Autistic Disorders; Rett's Disorder;
Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamine or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions;
Hallucinogen-Induced Mood Disorder; Hallucinogen-Induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic, Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified; Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Auxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
36. The use of claim 31 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
37. The use of claim 29 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
38. The use of claim 29 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
39. The use of claim 29 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
40. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
41. The use of claim 40 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
42. The use of claim 40 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
43. ~The use of claim 40 wherein the low plasma concentration variation comprises a change in plasma. concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
44. ~The use of claim 40 wherein the treatment is far excessive daytime sleepiness.
45. ~The use of claim 40 wherein the treatment is for a sleep disturbance.
46. ~The use as claimed in any one of claims 29 to 45, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
47. ~The use as claimed in. any one of claims 29 to 45, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
48. ~The use as claimed in claim 47, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
49. ~The use as claimed in any one of claims 29 to 48, wherein the pharmaceutical composition comprises an oral dosage form.
50. ~The use as claimed in claim 49, wherein the oral dosage form is an extended release dosage form.
51. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
52. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition. providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
53. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
54. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
55. The use of any one of claims 51 to 54 wherein the treatment is for excessive daytime sleepiness.
56. The use of any one of claims 51 to 54 wherein the treatment is for a sleep disturbance.
57. The use of any one of claims 51 to 54 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
58. The use of any one of claims 51 to 54 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
59. The use of any one of claims 51 to 54 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II disorder.
60, The use of any one of claims 51 to 54 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation;
Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation;
Mental Retardation Severity Unspecified; Autistic Disorders; Rett's Disorder, Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-reduced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamino or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions;
Hallucinogen-Induced Mood Disorder; Hallucinogen-Induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamino Related Disorder Not Otherwise Specified; Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
61. The use of claim 56 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severs, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
62. ~The use of any one of claims 51 to 54 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
63. ~The use of any one of claims 51 to 54 wherein the low plasma concentration variation comprises a change in plasma concentration. (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
64. ~The use of any one of claims 51 to 54 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
65. ~The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Mayor Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
65. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected, from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
67. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Magic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
68. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type., Schizophrenia, Disorganized; Schizophrenia, Catatonic lope; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder hue to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
69. The use of any one of claims 65 to 68 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
70. The use of any one of claims 65 to 68 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
71. The use of any one of claims 65 to 68 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
72. The use of any one of claims 65 to 68 wherein the treatment is for excessive daytime sleepiness.
73. The use of any one of claims 65 to 68 wherein the treatment is for a sleep disturbance.
74. The use as claimed in any one of claims 51 to 73, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
75. The use as claimed in any one of claims 51 to 73, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
76. The use as claimed in claim 75, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
77. The use as claimed in any one of claims 51 to 76, wherein the pharmaceutical composition comprises an oral dosage form.
78. The use as claimed in claim 77, wherein the oral dosage form is an extended release dosage form.
79. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carries, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
80. The use of claim 79 wherein the ireatmerat is fox excessive daytime sleepiness.
81. The use of claim 79 wherein the treatment is for a sleep disturbance.
82. The use of claim 79 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
83. The use of claim 79 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
84. The use of claim 79 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II
disorder.
85. The use of claim 79 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation.;
Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ; Autistic Disorders; Rett's Disorder;
Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type;
Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type;
Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type;
Attention-Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescentt Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder;
Tic Disorder NOS; Alcohol Intoxication Delirium; Alcohol Withdrawal Delirium;
Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication; Amphetamine or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations; Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium; Hallucinogen-Induced psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions;
Hallucinogen, Induced Mood Disorder; Hallucinogen-induced Anxiety Disorder;
Hallucinogen-Related Disorder Not Otherwise Specified; Inhalant Intoxication;
Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations);
Inhalant-reduced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations; Opioid-Induced Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions;
Phencyclidine [PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified; Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium;
Sedation, Hypnotic or Anxiolytic Withdrawal Delirium; Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions;
Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations;
Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication;
Other, or Unknown, Substance-Induced Delirium; Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder-.--.-with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder; Anxiety Disorder Not Otherwise Specified;
Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis;
Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania;
Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe. without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
86. The use of claim 81 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder;
Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type; Schizophrenia, Residual Type;
Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder;
Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features;
Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II
Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid;
Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
87. The use of claim 79 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent, 88. The use of claim 79 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
89. The use of claim 79 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
90. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the manufacture of a medicament for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
91. The use of claim 90 wherein the low plasma concentration variation.
comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
92. The use of claim 90 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
93. The use of claim 90 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
94. The use of claim 90 wherein the treatment is for excessive daytime sleepiness.
95. The use of claim 90 wherein the treatment is for a sleep disturbance.
96. The use as claimed in any one of claims 79 to 95, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
97. The use as claimed in any one of claims 79 to 95, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
98. The use as claimed in claim 97, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
99. The use as claimed in any one of claims 79 to 98, wherein the pharmaceutical composition comprises an oral dosage form.
100. The use as claimed in claim 99, wherein the oral dosage form is an extended release dosage form.
101. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
102. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in creed thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
103. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
104. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for tho treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
105. The pharmaceutical composition of any one of claims 101 to 104 wherein the treatment is for excessive daytime sleepiness.
106. The pharmaceutical composition of any one of claims 101 to 104 wherein the treatment is for a sleep disturbance.
107, The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
108. The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
109. The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I disorder and Bipolar II disorder.
110. The pharmaceutical composition of any one of claims 101 to 104 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation; Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ;
Autistic Disorders; Rett's Disorder; Childhood Disintegrative Disorders;
Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type; Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type; Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type; Attention-Deficit/Hyperactivity Disorder NOS;
Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder;
Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type;
Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder; Tic Disorder NOS; Alcohol Intoxication Delirium;
Alcohol Withdrawal Delirium; Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication;
Amphetamine ar Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional;
Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations;
Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium;
Hallucinoben-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Mood Disorder;
Hallucinogen-Induced Anxiety Disorder; Hallucinogen-Related Disorder Not Otherwise Specified;
Inhalant Intoxication; Inhalant Intoxication Delirium; Inhalant-Induced Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations); Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise-Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions;
Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations;
Opioid-Inducal Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delirium; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified;
Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic Intoxication Delirium; Sedation, Hypnotic or Anxiolytic Withdrawal Delirium;
Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations; Sedation, Hypnotic ar Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic or Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication; Other, or Unknown, Substance-Induced Delirium;
Other, or Unknown, Substance-Induced Persisting Dementia; Other, or Unknown, Substance-Induced Psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder;
Anxiety Disorder Not Otherwise Specified; Body Dysmorphic Disorder; Hypochondriasis, or Hypochondriacal Neurosis; Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania; Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
111. The pharmaceutical composition of claim 106 wherein psychiatric patient has a mental disorder or mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized;
Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise; Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and. Personality Disorders, Borderline.
112. The pharmaceutical composition of any one of claims 101 to 104 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
113. The pharmaceutical composition of any one of claims 101 to 104 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
114. The pharmaceutical composition of any one of claims 101 to 104 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
115. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features; ..
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
116. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
117. A pharmaceutical composition comprising a therapeutically effective amount of as enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual. Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief psychotic Disorder; Shared Psychotic Disorder;
psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
118. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
119. The pharmaceutical composition of any one of claims 115S to 118 wherein the l.aw plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
120. The pharmaceutical composition of any one of claims 115 to 118 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
121. The pharmaceutical composition of any one of claims 115 to 118 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
122. The pharmaceutical composition of any one of claims 115 to 118 wherein the treatment is for excessive daytime sleepiness.
123. The pharmaceutical composition of any one of claims 115 to 118 wherein the treatment is for a sleep disturbance.
124. The pharmaceutical composition as claimed in any one of claims 101 to 123, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
125. The pharmaceutical composition as claimed in any one of claims 101 to 123, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
126. The pharmaceutical composition as claimed in claim 125, wherein the therapeutically effective mount is from about 3 mg to about 12 mg.
127. The pharmaceutical composition as claimed in any one of claims 101 to 126, wherein the pharmaceutical composition comprises an oral dosage form.
128. The pharmaceutical composition as claimed in claim 127, wherein the oral dosage form is an extended release dosage form.
129. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
130. The pharmaceutical composition of claim 129 wherein the treatment is for excessive daytime sleepiness.
131. The pharmaceutical composition of claim 129 wherein the treatment is for a sleep disturbance.
132. The pharmaceutical composition of claim 129 wherein the psychiatric patient lies a mental disorder or mental illness selected from the group consisting of schizophrenia, bipolar diseases and other disease states in which psychosis aggressive behavior anxiety or depression is evidenced.
133. The pharmaceutical composition of claim 129 wherein the psychiatric patient has a schizophrenia type mental disorder or mental illness selected from the group consisting of schizophrenia, schizoaffective disorder and schizophreniform disorders.
134. The pharmaceutical composition of claim 129 wherein the psychiatric patient has a bipolar mental disorder or mental illness selected from the group consisting of Bipolar I
disorder and Bipolar II disorder.
135. The pharmaceutical composition of claim 129 wherein the psychiatric patient has a mental disorder or mental illness selected from the group consisting of Mild Mental Retardation; Moderate Mental Retardation; Severe Mental Retardation; Profound Mental Retardation; Mental Retardation Severity Unspecified ; Autistic Disorders;
Rett's Disorder; Childhood Disintegrative Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Attention-Deficit/Hyperactivity Disorder Combined Type; Attention-Deficit/Hyperactivity Disorder Predominately Inattentive Type; Attention-Deficit/Hyperactivity Disorder Predominately Hyperactive-Impulsive Type; Attention/Deficit/Hyperactivity Disorder NOS; Conduct Disorder, Childhood-Onset and Adolescent Type; Oppositional Defiant Disorder; Disruptive Behavior Disorder Not Otherwise Specified; Solitary Aggressive Type; Conduct Disorder, Undifferentiated Type; Tourette's Disorder; Chronic Motor Or Vocal Tic Disorder; Transient Tic Disorder; Tic Disorder NOS; Alcohol Intoxication Delirium;
Alcohol Withdrawal Delirium; Alcohol-Induced Persisting Dementia; Alcohol-Induced Psychotic Disorder with Delusions; Alcohol-Induced Psychotic Disorder with Hallucinations; Amphetamine or Similarly Acting Sympathomimetic Intoxication;
Amphetamine or Similarly Acting Sympathomimetic Delirium; Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Delusional;
Amphetamine or Similarly Acting Sympathomimetic Induced Psychotic with Hallucinations;
Cannabis-Induced Psychotic Disorder with Delusions; Cannabis-Induced Psychotic Disorder with Hallucinations; Cocaine Intoxication; Cocaine Intoxication Delirium; Cocaine-Induced Psychotic Disorder with Delusions; Cocaine-Induced Psychotic Disorder with Hallucinations; Halluciogen Intoxication Hallucinogen Intoxication Delirium;
Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Psychotic disorder with Delusions; Hallucinogen-Induced Mood Disorder;
Hallucinogen-Induced Anxiety Disorder; Hallucinogen-Related Disorder Not Otherwise Specified;
Inhalant Intoxication; Inhalant Intoxication Delirium; Inhalant-Induced.
Persisting Dementia; Inhalant-Induced Psychotic Disorder with Delusions; Inhalant-Induced Psychotic with Hallucinations); Inhalant-Induced Mood Disorder; Inhalant-Induced Anxiety Disorder; Inhalant-Related Disorder Not Otherwise Specified; Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Delusions;
Opioid Intoxication Delirium; Opioid-Induced Psychotic Disorder with Hallucinations;
Opioid-Induced Mood Disorder; Phencyclidine (PCP) ar Similarly Acting Arylcyclohexylamine Intoxication; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Intoxication Delixium; Phencyclidine (PCp) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Delusions; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Psychotic Disorder with Hallucinations Phencyclidine (pCp) or Similarly Acting Arylcyclohexylamine Mood Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Induced Anxiety Disorder; Phencyclidine (PCP) or Similarly Acting Arylcyclohexylamine Related Disorder Not Otherwise Specified;
Sedative, Hypnotic or Anxiolytic Intoxication; Sedation, Hypnotic or Anxiolytic-Intoxication Delirium; Sedation, Hypnotic or Anxiolytic Withdrawal Delirium;
Sedation, Hypnotic or Anxiolytic Induced Persisting Dementia; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Delusions; Sedation, Hypnotic or Anxiolytic-Induced Psychotic Disorder with Hallucinations; Sedation, Hypnotic or Anxiolytic-Induced Mood Disorder; Sedation, Hypnotic ar Anxiolytic-Induced Anxiety Disorder; Other, or Unknown, Substance Intoxication; other, or Unknown, Substance-Induced Delirium;
Other, or Unknown, Substance-Induced persisting Dementia; Other, or Unknown, Substance-Induced psychotic Disorder with Delusions; Other, or Unknown, Substance-Induced Psychotic Disorder with Hallucinations; Other, or Unknown, Substance-Induced Mood Disorder; Other, or Unknown, Substance-Induced Anxiety Disorder; Other, or Unknown, Substance Disorder Not Otherwise Specified; Obsessive Compulsive Disorder; Post-traumatic Stress Disorder; Generalized Anxiety Disorder;
Anxiety Disorder Not Otherwise Specified; Body Dysmorphic Disorder; Hypochondriasis, or hypochondriacal Neurosis; Somatization Disorder; Undifferentiated Somatoform Disorder; Somatoform Disorder Not Otherwise Specified; Intermittent Explosive Disorder; Kleptomania; Pathological Gambling; Pyromania; Trichotillomania; and Impulse Control Disorder NOS; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized; Schizophrenia, Catatonic Type ; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
136. The pharmaceutical composition of claim 131 wherein psychiatric patient has a mental disorder or mental illness selected from the soup consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type; Schizophrenia, Disorganized;
Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder; Psychotic Disorder Due to a General Medical Condition with Delusions Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified;
Major Depression, Single Episode, Severs, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar. Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, Paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
137. The pharmaceutical composition of claim 129 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
138. The pharmaceutical composition of claim 129 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 14 percent to about 30 percent.
139. The pharmaceutical composition of claim 129 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
140. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for the treatment of excessive daytime sleepiness and/or a sleep disturbance in a psychiatric patient in need thereof, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment, said psychiatric patient having a mental illness selected from the group consisting of Post traumatic Stress Disorder; Schizophrenia, Paranoid Type,;
Schizophrenia, Disorganized; Schizophrenia, Catatonic Type; Schizophrenia, Undifferentiated Type;
Schizophrenia, Residual Type; Schizophreniform Disorder; Schizoaffective Disorder;
Delusional Disorder; Brief Psychotic Disorder; Shared Psychotic Disorder;
Psychotic Disorder Due to a General Medical Condition with Delusions; Psychotic Disorder Due to a General Medical Condition with Hallucinations; Psychotic Disorders Not Otherwise Specified; Major Depression, Single Episode, Severe, without Psychotic Features; Major Depression, Recurrent, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, without Psychotic Features; Bipolar Disorder, Mixed, Severe, with Psychotic Features; Bipolar Disorder, Manic, Severe, without Psychotic Features; Bipolar Disorder, Manic, Severe, with Psychotic Features; Bipolar Disorder, Depressed, Severe, without Psychotic Features; Bipolar Disorder, Depressed, Severe, with Psychotic Features;
Bipolar II Disorder; Bipolar Disorder Not Otherwise Specified; Personality Disorders, paranoid; Personality Disorders, Schizoid; Personality Disorders, Schizotypal;
Personality Disorders, Antisocial; and Personality Disorders, Borderline.
141. The pharmaceutical composition of claim 140 wherein the low plasma concentration variation comprises a change in plasma concentration. (Cmax-Cmin/Cmax) of less than about 30 percent.
142. The pharmaceutical composition of claim 140 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
143. The pharmaceutical composition of claim 140 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
144. The pharmaceutical composition of claim 140 wherein the treatment is for excessive daytime sleepiness.
145. The pharmaceutical composition of claim 140 wherein the treatment is for a sleep disturbance, 146. The pharmaceutical composition as claimed in any one of claims 129 to 145, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
147. The pharmaceutical composition as claimed in any one of claims 129 to 145, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
148. The pharmaceutical composition as claimed in claim 147, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
149. The pharmaceutical composition as claimed in any one of claims 129 to 148, wherein the pharmaceutical composition comprises an oral dosage form.
150. The pharmaceutical composition as claimed in claim 149, wherein the oral dosage form is an extended release dosage form, 151. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the sympthoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
152. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
153. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
154. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
155. The use of any one of claims 151 to 154 wherein the treatment is for excessive daytime sleepiness.
156. The use of any one of claims 151 to 154 wherein the treatment is for a sleep disturbance.
157. The use of any one of claims 151 to 154 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
158. The use of any one of claims 151 to 154 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
159. The use of any one of claims 151 to 154 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
160. The use as claimed in any one of claims 151 to 159, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
161. The use as claimed in any one of claims 151 to 159, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
162. The use as claimed in claim 161, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
163. The use as claimed in any one of claims 151 to 162, wherein the pharmaceutical composition comprises an oral dosage form.
164. The use as claimed in claim 163, Wherein the oral dosage form is an extended release dosage form.
165. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
166. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
167. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
168. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
169. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
170. The use of any one of claims 166 to l69 wherein the treatment is for excessive daytime sleepiness.
171. The use of any one of claims 166 to 169 wherein the treatment is for a sleep disturbance.
172. The use of any one of claims 166 to 169 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
173. The use of any one of claims 166 to 169 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
174. The use of any one of claims 166 to 169 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
175. The use as claimed in any one of claims 166 to 174, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
176. The use as claimed in any one of claims 166 to 174, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
177. The use as claimed in claim 176, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
178. The use as claimed in any one of claims 166 to 177, wherein the pharmaceutical composition comprises an oral dosage form.
179. The use as claimed in claim 178, wherein the oral dosage form is an extended release dosage form.
180. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein.
the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
181. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
182. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
183. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
184. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
185. The use of any one of claims 181 to 184 wherein the treatment is for excessive daytime sleepiness.
186. The use of any one of claims 181 to 184 wherein the treatment is for a sleep disturbance.
187, The use of any one of claims 181 to 184 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
188. The use of any one of claims 181 to 184 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
189. The use of any one of claims 181 to 184 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
190. The use as claimed in any one of claims 181 to 189, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
191. The use as claimed in any one of claims 181 to 189, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
192. The use as claimed in claim 191, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
193. The use as claimed in any one of claims 181 to 192, wherein the pharmaceutical composition comprises an oral dosage form.
194. The use as claimed in claim 193, wherein the oral dosage form is an extended release dosage form.
195. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
195. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
197. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
198. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
199. The use of any one of claims 195 to 198 wherein the treatment is for excessive daytime sleepiness.
200. The use of any one of claims 196 to 198 wherein the treatment is for a sleep disturbance.
201. The use of any one of claims 196 to 198 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
202. The use of any one of claims 196 to 198 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
203. The use of any one of claims 19G to 198 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
204. The use as claimed in any one of claims 196 to 203, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
205. The use as claimed in any one of claims 196 to 203, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
206. The use as claimed in claim 205, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
207. The use as claimed in any one of claims 196 to 206, wherein the pharmaceutical.
composition comprises an oral dosage form.
208. The use as claimed in claim 207, wherein the oral dosage form is an extended release dosage form.
209. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
210. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
211. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
212. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
213. The use of any one of claims 209 to 212 wherein the treatment is for excessive daytime sleepiness.
214. The use of any one of claims 209 to 212 wherein the treatment is for a sleep disturbance.
215. The use of any one of claims 209 to 212 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
216. The use of. my one of claims 209 to 212 wherein the low plasma concentration variation. comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
217. The use of an.y one of claims 209 to 212 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
218. The use as claimed in any one of claims 209 to 217, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
219. The use as claimed in any one of claims 209 to 217, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
220. The use as claimed in claim 219, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
221. The use as claimed in any one of claims 209 to 220, wherein the pharmaceutical composition comprises an oral dosage form.
222. The use as claimed in claim 221, wherein the oral dosage form is an extended release dosage form.
223. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
224. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient 1n need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
225. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament far improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
226. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition ,providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
227. The use o:f a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
228. The use of any one of claims 224 to 227 wherein the treatment is for excessive daytime sleepiness.
229. The use of any one of claims 224 to 227 wherein the treatment is for a sleep disturbance.
230. The use of any one of claims 224 to 727 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
231. The use of any one of claims 224 to 227 wherein the low plasma concentration.
variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
232. The me of any one of claims 224 to 227 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
233. The use as claimed in any one of claims 224 to 232, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
234. The use as claimed in any one of claims 224 to 232, wherein the therapeutically effective amount is from about 4.25 mg to about 20 mg.
235. The use as claimed in claim 234, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
236. The use as claimed in any one of claims 224 to 235, wherein the pharmaceutical composition comprises an oral dosage form.
237. The use as claimed in claim 236, wherein the oral dosage form is an extended release dosage form.
238. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
239. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
240. The use of a pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
241. The use of a pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament far improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
242. The use of a pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
243. The use of any one of claims 239 to 242 wherein the treatment is for excessive daytime sleepiness.
244. The use of any one of claims 239 to 242 wherein the treatment is for a sleep disturbance.
245. The use of any one of claims 239 to 242 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
246. The use of any one of claims 239 to 242 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
247. The use of any one of claims 239 to 242 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 25 percent.
248. The use as claimed in any one of claims 239 to 247, wherein the therapeutically affective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
249. The use as claimed in any one of claims 239 to 247, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
250. The use as claimed in claim 249, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
251. The use as claimed in any one of claims 239 to 250, wherein the pharmaceutical composition comprises an oral dosage form.
252. The use as claimed in claim 251, wherein the oral dosage form is an extended release dosage form.
253. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
254. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
255. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of bipolar disorder in a psychiatric patient in need thereof wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
256. The use of a pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, in the preparation of a medicament for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof wherein the symptoms are selected from the group consisting or sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
257. The use of any one of claims 254 to 256 wherein the treatment is for excessive daytime sleepiness.
258. The use of any one of claims 2S4 to 256 wherein the treatment is for a sleep disturbance.
259. The use of any one of claims 254 to 256 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
260. The use of any one of claims 254 to 256 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about percent to about 30 percent.
261. The use of any one of claims 254 to 256 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
262. The use as claimed in any one of claims 254 to 261, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
263. The use as claimed in any one of claims 254 to 261, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
264. The use as claimed in claim 263, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
265. The use as claimed in any one of claims 254 to 264, wherein the pharmaceutical composition comprises an oral dosage form.
266. The use as claimed in claim 265, wherein the oral dosage form is an extended release dosage form.
267. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
268. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
269. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
270. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected, from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
271. The pharmaceutical composition of any one of claims 267 to 270 wherein the treatment is for excessive daytime sleepiness.
272. The pharmaceutical composition of any one of claims 267 to 270 wherein the treatment is for a sleep disturbance.
273. The pharmaceutical composition of any one of claims 267 to 270 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
274. The pharmaceutical composition of any one of claims 267 to 270 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
275. The pharmaceutical composition of any one of claims 267 to 270 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
276. The pharmaceutical composition as claimed in any one of claims 267 to 275, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
277. The pharmaceutical composition as claimed in any one of claims 267 to 275, wherein the therapeutically effective amount is from about 0.25 mg to about 20 m.g.
278. The pharmaceutical composition as claimed in claim 277, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
279. The pharmaceutical composition as claimed in any one of claims 267 to 278, wherein the pharmaceutical composition comprises an oral dosage form.
280. The pharmaceutical composition as claimed in claim 279, wherein the oral dosage form is an extended release dosage form.
281. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
282. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
283. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
284. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
285. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively law plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
286. The pharmaceutical composition of any one of claims 282 to 285 wherein the treatment is for excessive daytime sleepiness.
287. The pharmaceutical composition of any one of claims 282 to 285 wherein the treatment is for a sleep disturbance.
288. The pharmaceutical composition of any one of claims 282 to 285 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
289. The pharmaceutical composition of any one of claims 282 to 285 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 1.0 percent to about 30 percent.
290. The pharmaceutical composition of any one of claims 282 to 285 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
291. The pharmaceutical composition as claimed in any one of claims 282 to 290, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
292. The pharmaceutical composition as claimed in any one of claims 282 to 290, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
293. The pharmaceutical composition as claimed in claim 292, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
294. The pharmaceutical composition as claimed in any one of claims 282 to 293, wherein the pharmaceutical composition comprises an oral dosage form.
295. The pharmaceutical composition as claimed in claim 294, wherein the oral dosage form is an extended release dosage form.
296. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
297. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
298. A pharmaceutical composition comprising a therapeutically effective amount of a pharmaceutically acceptable acid addition salt of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
299. A pharmaceutical composition comprising a therapeutically effective amount of an enantiomeric form of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
300. A pharmaceutical composition comprising a therapeutically effective amount of an ester of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
301. The pharmaceutical composition of any one of claims 297 to 300 wherein the treatment is for excessive daytime sleepiness.
302. The pharmaceutical composition of any one of claims 297 to 300 wherein the treatment is for a sleep disturbance.
303. The pharmaceutical composition of any one of claims 297 to 300 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
304. The pharmaceutical composition of any one of claims 297 to 300 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
305. The pharmaceutical composition of any one of claims 297 to 300 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 1,5 percent to about 25 percent.
306. The pharmaceutical composition as claimed in any one of claims 297 to 305, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
307. The pharmaceutical composition as claimed in any one of claims 297 to 305, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
308. The pharmaceutical composition as claimed in claim 307, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
309. The pharmaceutical composition as claimed in any one of claims 297 to 308, wherein the pharmaceutical composition comprises an oral dosage form.
310. The pharmaceutical composition as claimed in claim 309, wherein the oral dosage form is an extended release dosage form.
311. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition comprising an extended release oral dosage form and providing a relatively low plasma concentration. variation of paliperidone to the psychiatric patient in need of treatment.
312. A pharmaceutical. composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of schizophrenia in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
313. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of bipolar disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
314. A pharmaceutical composition comprising a therapeutically effective amount of paliperidone palmitate, together with a pharmaceutically acceptable carrier, for improving symptoms of schizoaffective disorder in a psychiatric patient in need thereof, wherein the symptoms are selected from the group consisting of sleep disturbances and excessive daytime sleepiness, the pharmaceutical composition providing a relatively low plasma concentration variation of paliperidone to the psychiatric patient in need of treatment.
315. The pharmaceutical composition of any one of claims 312 to 314 wherein the treatment is for excessive daytime sleepiness.
316. The pharmaceutical composition of any one of claims 312 to 314 wherein the treatment is for a sleep disturbance.
317. The pharmaceutical composition of any one of claims 312 to 314 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of less than about 30 percent.
318. The pharmaceutical composition of any one of claims 312 to 314 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 10 percent to about 30 percent.
319. The pharmaceutical composition of any one of claims 312 to 314 wherein the low plasma concentration variation comprises a change in plasma concentration (Cmax-Cmin/Cmax) of from about 15 percent to about 25 percent.
320. The pharmaceutical composition as claimed in any one of claims 312 to 319, wherein the therapeutically effective amount is from about 0.01 mg/kg to about 2 mg/kg body weight.
321. The pharmaceutical composition as claimed in any one of claims 312 to 319, wherein the therapeutically effective amount is from about 0.25 mg to about 20 mg.
322. The pharmaceutical composition as claimed in claim 321, wherein the therapeutically effective amount is from about 3 mg to about 12 mg.
323. The pharmaceutical composition as claimed in any one of claims 312 to 322, wherein the pharmaceutical composition comprises an oral dosage form.
324. The pharmaceutical composition as claimed in claim 323, wherein the oral dosage form is an extended release dosage form.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78876406P | 2006-04-03 | 2006-04-03 | |
| US60/788,764 | 2006-04-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2558704A1 true CA2558704A1 (en) | 2006-11-29 |
Family
ID=37480450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2558704 Abandoned CA2558704A1 (en) | 2006-04-03 | 2006-09-22 | Use of paliperidone for the treatment of sleep disturbances and/or excessive daytime sleepiness in psychiatric patients |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101460143A (en) |
| CA (1) | CA2558704A1 (en) |
-
2006
- 2006-09-22 CA CA 2558704 patent/CA2558704A1/en not_active Abandoned
-
2007
- 2007-03-30 CN CNA2007800203023A patent/CN101460143A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN101460143A (en) | 2009-06-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |