Modified-release dosage forms of 5-HT2C agonists useful for weight management

Patent metadata

Field	Value
Publication number	US-10463676-B2
Application number	US-201916241337-A
Country	US
Kind code	B2
Filing date	Jan 7, 2019
Priority date	Sep 1, 2010
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

The present invention relates to methods for weight management that utilize modified-release dosage forms comprising (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine salts and crystalline forms thereof. The present invention further relates to (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine salts, crystalline forms thereof and modified-release dosage forms comprising them.

First claim

What is claimed is:

1. A method of weight management in an individual in need thereof comprising administering once daily to said individual a modified-release dosage form which is a tablet, wherein the dosage form comprises a core tablet and a functional film coating, wherein said core tablet comprises:
(i) about 7% by weight of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride salt hemihydrate, Form III, and
(ii) about 50% by weight of (hydroxypropyl)methyl cellulose;
wherein said functional film coating comprises ethyl cellulose and (hydroxypropyl)methyl cellulose in a weight ratio of about 85:15; and
wherein said modified-release dosage form provides an in vitro release rate for which the time to achieve 80% release of said (R) 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (T80%) is at least 3 hours as determined by USP Apparatus I Basket Method in 900 mL of 0.1 N HCl solution at 37° C. and 100 rpm.

2. The method of claim 1 , wherein the weight to weight ratio of said core tablet to said functional coating is about 20:1.

3. The method of claim 1 or 2 , wherein the core tablet further comprises microcrystalline cellulose.

4. The method of claim 3 , wherein the core tablet comprises about 20% by weight of microcrystalline cellulose.

5. The method of claim 1 or 2 , wherein the dosage form exhibits a release profile comprising super-case II kinetics under in vitro conditions.

6. The method of claim 1 or 2 , wherein the core tablet further comprises mannitol.

7. The method of claim 1 or 2 , wherein the core tablet further comprises magnesium stearate.

8. The method of claim 1 , wherein said weight management comprises one or more of: weight loss, maintenance of weight loss, decreased food consumption, increasing meal-related satiety, reducing pre-meal hunger, and reducing intra-meal food intake.

9. The method of claim 1 , as an adjunct to diet and exercise.

10. The method of claim 1 , wherein said individual in need of weight management is selected from: an obese patient with an initial body mass index≥30 kg/m 2 ; an overweight patient with an initial body mass index≥27 kg/m 2 in the presence of at least one weight related comorbid condition; and an overweight patient with an initial body mass index≥27 kg/m 2 in the presence of at least one weight related comorbid condition; wherein said weight related co-morbid condition is selected from: hypertension, dyslipidemia, cardiovascular disease, glucose intolerance, and sleep apnea.

11. The method of claim 1 , further comprising administering a second anti-obesity agent to said individual.

12. The method of claim 1 , wherein said second anti-obesity agent is selected from: chlorphentermine, clortermine, phenpentermine, and phentermine, and pharmaceutically acceptable salts, solvates, and hydrates thereof.

13. The method of claim 1 , further comprising administering an anti-diabetes agent to said individual.

14. The method of claim 1 , wherein said anti-diabetes agent is metformin.

15. The method of claim 1 , wherein the amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride salt hemihydrate, Form III is 20.8 mg per tablet.

Assignees

• Arena Pharm Inc

Inventors

• Shao Zezhi Jesse
• Blackburn Anthony C
• Grottick Andrew J
• Morgan Michael E
• Rueter Jaimie Karyn
• Shifrina Anna
• Stirn Scott
• Yang Libo
• Yoon Woo Hyun

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K31/155

  Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A23P20/12

  Apparatus or processes for applying powders or particles to foodstuffs, e.g. for breading; Such apparatus combined with means for pre-moistening or battering · CPC title

• A61K31/55 Primary

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title