WO2010008719A9 - Formulations pharmaceutiques orales d’antagonistes de vla-4 - Google Patents

Formulations pharmaceutiques orales d’antagonistes de vla-4 Download PDF

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Publication number
WO2010008719A9
WO2010008719A9 PCT/US2009/047353 US2009047353W WO2010008719A9 WO 2010008719 A9 WO2010008719 A9 WO 2010008719A9 US 2009047353 W US2009047353 W US 2009047353W WO 2010008719 A9 WO2010008719 A9 WO 2010008719A9
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical formulation
compound
fatty acid
vla
dose
Prior art date
Application number
PCT/US2009/047353
Other languages
English (en)
Other versions
WO2010008719A2 (fr
WO2010008719A3 (fr
Inventor
David Harris
Ramya Kumbale
Original Assignee
Schering Corporation
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 Schering Corporation filed Critical Schering Corporation
Publication of WO2010008719A2 publication Critical patent/WO2010008719A2/fr
Publication of WO2010008719A3 publication Critical patent/WO2010008719A3/fr
Publication of WO2010008719A9 publication Critical patent/WO2010008719A9/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the present invention provides pharmaceutical formulations suitable for oral administration comprising a granulate comprising a VLA-4 antagonist that is Compound I or a pharmaceutically acceptable salt thereof, a surfactant, a binder, a disintegrant, and a diluent, wherein the VLA-4 antagonist comprises about 5% to 50% by weight of the pharmaceutical formulation.
  • capsules of exemplary formulation D were packaged as 10 capsules per bottle in induction-sealed HDPE bottle with child- resistant caps. Samples were stored at 25 0 C and 60% relative humidity up to 1 year or 40 0 C and 75% relative humidity up to 6 months. Following storage under the aforementioned conditions, samples were pulled at various time points (e.g., 1 month, 3 months, 6 months, 9 months, 12 months) and assessed for moisture content (using volumetric Karl Fischer titration method), label strength, and the presence of Compound IA degradation products.
  • ECGs were obtained on Days -1 and 1, and these ECGs were machine read with over-reading by the investigator.
  • blood samples were collected predose (0 hour), 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose.
  • metabolite profiling blood samples were collected predose (0 hour), 2 and 6 hours postdose, and urine was collected from 0 to 24 hours postdose.
  • Whole blood was collected predose (0 hour), 2 and 6 hours postdose to explore the effect of Compound IA on the expression of cell surface markers and the relative abundance of lymphocyte subtypes in peripheral blood using FACS analyses.
  • Multiple blood samples were collected on Days -1 and 1 in a time-matched manner to determine the peripheral lymphocyte counts.
  • Test Product, Dose, Mode of Administration Compound IA, 50 mg capsules (specifically, capsules of comparative formulation F described in Table IB above) and 200 mg capsules (specifically, capsules of exemplary formulation D described in Table IA above).
  • Doses administered were: 1 x 50 mg (total 50 mg), 3 x 50 mg (total 150 mg), 6 x 50 mg (total 300 mg), 3 x 200 mg (total 600 mg), and 5 x 200 mg (total 1000 mg).
  • the study drug was administered orally.
  • Compound IA pharmaceutical formulations described herein provided sufficient bioavailability following oral administration at a single dose >150 mg to elicit a modest increase in peripheral circulating lymphocytes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des formulations pharmaceutiques orales comprenant un antagonistes de VLA-4 et un tensioactif. Dans un mode de réalisation préféré, l’antagoniste de VLA-4 est le sel monosodique d’acide (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-méthyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-méthylphényl)propanoïque. La présente invention concerne en outre des procédés pour traiter et/ou prévenir et/ou inhiber la progression d’une maladie inflammatoire utilisant de telles formulations pharmaceutiques.
PCT/US2009/047353 2008-06-16 2009-06-15 Formulations pharmaceutiques orales d’antagonistes de vla-4 WO2010008719A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6185708P 2008-06-16 2008-06-16
US61/061,857 2008-06-16

Publications (3)

Publication Number Publication Date
WO2010008719A2 WO2010008719A2 (fr) 2010-01-21
WO2010008719A3 WO2010008719A3 (fr) 2010-03-11
WO2010008719A9 true WO2010008719A9 (fr) 2010-07-01

Family

ID=41395474

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/047353 WO2010008719A2 (fr) 2008-06-16 2009-06-15 Formulations pharmaceutiques orales d’antagonistes de vla-4

Country Status (1)

Country Link
WO (1) WO2010008719A2 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3810085A1 (fr) 2018-06-20 2021-04-28 Progenity, Inc. Traitement d'une maladie du tractus gastro-intestinal par un inhibiteur de l'intégrine

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2761266B1 (fr) * 1997-03-28 1999-07-02 Sanofi Sa Composition pharmaceutique formee par granulation humide pour l'administration orale d'un derive du n-piperidino-3- pyrazolecarboxamide, de ses sels et de leurs solvates
UA72207C2 (uk) * 1998-04-07 2005-02-15 Брістол- Майєрс Сквібб Фарма Компані Фармацевтична композиція ефавіренцу з добавкою дезінтегруючих агентів у вигляді швидкорозчинних капсул або таблеток та спосіб її виготовлення
WO2003039516A1 (fr) * 2001-11-07 2003-05-15 Fujisawa Pharmaceuticla Co., Ltd. Procede pour ameliorer la dissolution de medicaments a faible pouvoir de dissolution
CA2513493A1 (fr) * 2002-11-08 2004-05-27 Schering Corporation Produits de combinaison comprenant des derives d'acide carboxylique inhibant la liaison des integrines a leurs recepteurs et autres composes therapeutiques

Also Published As

Publication number Publication date
WO2010008719A2 (fr) 2010-01-21
WO2010008719A3 (fr) 2010-03-11

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