WO1997048394A1 - Combinaison de ropinirole et de l-dopa servant a traiter la maladie de parkinson - Google Patents

Combinaison de ropinirole et de l-dopa servant a traiter la maladie de parkinson Download PDF

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Publication number
WO1997048394A1
WO1997048394A1 PCT/GB1997/001640 GB9701640W WO9748394A1 WO 1997048394 A1 WO1997048394 A1 WO 1997048394A1 GB 9701640 W GB9701640 W GB 9701640W WO 9748394 A1 WO9748394 A1 WO 9748394A1
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WO
WIPO (PCT)
Prior art keywords
dopa
disease
ropinirole
parkinson
treatment
Prior art date
Application number
PCT/GB1997/001640
Other languages
English (en)
Inventor
Diane Fuell
Original Assignee
Smithkline Beecham Plc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to JP10502504A priority Critical patent/JP2000513349A/ja
Priority to EP97926149A priority patent/EP0914117A1/fr
Publication of WO1997048394A1 publication Critical patent/WO1997048394A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil

Definitions

  • This invention relates to a method of treatment of early stage Parkinson's Disease patients, in particular the use of a combination of ropinirole and L-DOPA.
  • L-DOPA was first introduced over 25 years ago for the treatment of Parkinson's Disease and has since become the 'gold standard' for symptomatic therapy. Nevertheless, L- DOPA has disadvantages, primarily in terms of its long term motor complications. After several years treatment, patients experience a wearing off effect of L-DOPA at the end of dosing periods; these simple fluctuations may then develop into more complex on-off phenomenon where the patient may oscillate, sometimes rapidly and inconsistently, between being "on” (i.e. relatively free of Parkinsonian symptoms), and "off, or "frozen”. Additionally, long term L-DOPA therapy is associated with the emergence of dyskinesias which may be as disabling as the disease itself, and often limit the L-DOPA dose.
  • dopamine agonists such as bromocriptine, pergolide and lisuride have traditionally been used as adjunct therapy. These drugs have longer half-lives than L-DOPA and so are able to prolong its dopa ⁇ rinergic effects and smooth out the wearing-off of doses.
  • dopamine agonists When used as adjunct therapy, dopamine agonists have been shown to improve the anti- Parkinsonian efficacy of L-DOPA.
  • dopamine agonists have been used as monotherapy, to treat the early stages of the disease. There generally however comes a point in the treatment regimen when the addition of L-DOPA (so-called L-DOPA rescue) becomes necessary. Even so, the onset of L-DOPA associated complications is delayed in comparison with patients who are treated with L-
  • Ropinirole (4-(2-di-n-propylaminoethyl)-2(3H)-indolone) is the compound of formula (I):
  • the present invention provides a method of treatment for Parkinson's Disease which method comprises co-administering an effective amount of a combination of ropinirole and L-DOPA to a patient suffering from Parkinson's Disease.
  • the present invention further provides:- a) ropinirole for use in the treatment of Parkinson's Disease in combination with L-DOPA in which L-DOPA is used at a low dose, in comparison to that which would be used at a corresponding stage of the disease, if L-DOPA was being used as monotherapy;
  • L-DOPA for use in the treatment of Parkinson's Disease in combination with ropinirole in which L-DOPA is used at a low dose, in comparison to that which would be used at a corresponding stage of the disease, if L-DOPA was being used as monotherapy;
  • L-DOPA in the manufacture of a medicament for use in the treatment of Parkinson's Disease in combination with ropinirole in which L-DOPA is used at a low dose, in comparison to that which would be used at a corresponding stage of the disease, if L-DOPA was being used as monotherapy.
  • treatment in accordance with the invention is used at an early stage of the development of Parkinson's Disease in a patient.
  • a patient is initially titrated to an appropriate dosage of ropinirole, followed by the addtion of a low dosage of L-DOPA. The dosages of each may then be titrated according to an individual patients response, until an optimal therapeutic regimen is established.
  • L-DOPA is used at a low-dose, in comparison to that which would be used at a corresponding stage of the disease, if L-DOPA was being used as monotherapy.
  • Suitable low dosages are in the range 25 to 200mg/day, preferably 25 to 150, more preferably 50 to lOOmg/day.
  • the patient will be started on ropinirole at a low dosage, for instance 0.25mg tid and then titrated up towards 1.5mg tid, for instance over a three to six week period, in increments of 0.25mg, to allow for tolerance to develop to peripheral side effects such as vomitting and nausea.
  • L-DOPA is then added in, at a dosage of 50mg tid, and after a suitable period, for instance two weeks, to allow for stabilisation and to check against any unforeseen drug interactions, the dosage of ropinirole is again increased, for instance to 2mg tid.
  • the dosage of ropinirole may be increased further, for instance up to 8 mg tid, until no further beneficial therapeutic effect is seen, when the dosage of L-DOPA may be increased. It will however be appreciated that the response of individual patients varies and some may tolerate a more rapid rate of increase of dosage.
  • the optimum daily dosage of ropinirole and L-DOPA must be determined by careful titration for each patient. An appropriate regimen will be at the discretion of the physician.
  • L-DOPA is used at an initial dosage of for instance 250mg/day and this is then titrated up towards a normal dosage range of from 2 to 8g/day.
  • L-DOPA may be used alone or in combination with a peripheral decarboxylase inhibitor such as carbidopa (for instance Sinemet (Du Pont) or benserazide (for instance, Madopar, Roche).
  • a peripheral decarboxylase inhibitor such as carbidopa (for instance Sinemet (Du Pont) or benserazide (for instance, Madopar, Roche).
  • the separate dosages of L-DOPA and ropinirole will be taken by the patient at more or less the same time, and preferably three times a day.
  • L-DOPA may be used in any of the pharmaceutical formulations in which it is normally provided, for instance tablets. Each dosage may be made up of a single tablet or a combination of different tablets which may be of the same or different strengths.
  • Ropinirole may be used in any of the pharmaceutical formulations in which it is normally provided, for instance tablets. Each dosage may be made up of a single tablet or a combination of different tablets which may be of the same or different strengths. Ropinirole is preferably provided as the hydrochloride salt. In a further aspect, the present invention provides a kit comprising a first pharmaceutical formulation comprisng L-DOPA and a second pharmaceutical formulation comprising ropinirole.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Nouvelles combinaisons de ropinirole et de L-DOPA servant à traiter la maladie de Parkinson. On applique généralement ce traitement à un stade précoce de la maladie et on utilise la L-DOPA à faibles doses par rapport à celles qu'on utiliserait à un stade correspondant de la maladie si on utilisait la L-DOPA en monothérapie.
PCT/GB1997/001640 1996-06-19 1997-06-19 Combinaison de ropinirole et de l-dopa servant a traiter la maladie de parkinson WO1997048394A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP10502504A JP2000513349A (ja) 1996-06-19 1997-06-19 パーキンソン病の治療における使用のためのロピニロールおよびｌ―ｄｏｐａの組み合わせ
EP97926149A EP0914117A1 (fr) 1996-06-19 1997-06-19 Combinaison de ropinirole et de l-dopa servant a traiter la maladie de parkinson

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9612752.7A GB9612752D0 (en) 1996-06-19 1996-06-19 Novel treatment
GB9612752.7 1996-06-19

Publications (1)

Publication Number Publication Date
WO1997048394A1 true WO1997048394A1 (fr) 1997-12-24

Family

ID=10795500

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/001640 WO1997048394A1 (fr) 1996-06-19 1997-06-19 Combinaison de ropinirole et de l-dopa servant a traiter la maladie de parkinson

Country Status (4)

Country Link
EP (1) EP0914117A1 (fr)
JP (1) JP2000513349A (fr)
GB (1) GB9612752D0 (fr)
WO (1) WO1997048394A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000021550A2 (fr) * 1998-10-13 2000-04-20 President And Fellows Of Harvard College Methodes et compositions de traitement des maladies neurodegeneratives

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0299602A2 (fr) * 1987-05-21 1989-01-18 Smith Kline & French Laboratories Limited L'emploi de dérivés de l'indolone pour la fabrication de médicaments pour le traitement du parkinsonisme

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0299602A2 (fr) * 1987-05-21 1989-01-18 Smith Kline & French Laboratories Limited L'emploi de dérivés de l'indolone pour la fabrication de médicaments pour le traitement du parkinsonisme

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BROOKS ET AL: "ROPINIROLE INTHE SYMPTOMATIC TREATMENT OF PARKINSON'S DISEASE", J NEURAL TRASMISSION, vol. S45, 1995, WIEN, AUSTRIA, pages 231 - 238, XP002040492 *
RABEY J M: "SECOND GENERATION OF DOPAMINE AGONISTS: PROS AND CONS.", J NEURAL TRANSMISSION, vol. S45, 1995, WIEN , AUSTRIA, pages 231 - 224, XP002040493 *
RASCOL ET AL: "A PLACEBO-CONTROLLED STUDY OF ROPINIROLE, A NEW D2 AGONIST, IN THE TREATMENT OF MOTOR FLUCTUATIONS OF L-DOPA-TREATED PARKISONIAN PATIENTS", ADVANCES IN NEUROLOGY, vol. 69, 1996, PHILADELPHIA. USA, pages 531 - 534, XP002040494 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000021550A2 (fr) * 1998-10-13 2000-04-20 President And Fellows Of Harvard College Methodes et compositions de traitement des maladies neurodegeneratives
WO2000021550A3 (fr) * 1998-10-13 2000-07-27 Harvard College Methodes et compositions de traitement des maladies neurodegeneratives

Also Published As

Publication number Publication date
GB9612752D0 (en) 1996-08-21
EP0914117A1 (fr) 1999-05-12
JP2000513349A (ja) 2000-10-10

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