COMPOSITIONS AND METHODS FOR TREATING OBESITY AND RELATED DISORDERS

• US 20080255093A1
• Filed: 04/29/2008
• Published: 10/16/2008
• Est. Priority Date: 06/14/1999
• Status: Abandoned Application

• Current Assignee: Vivus Incorporated
• Original Assignee: Vivus Incorporated
• Inventors: Wilson, Leland F., Tam, Peter Y.
• Application Number:
  US12/111,793
• Publication Number:
  US 20080255093A1
• Time in Patent Office: Days
• US Class Current: 514/217.01
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/133 having hydroxy groups, e.g. sphingosine
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present invention is drawn to combinations of pharmaceutical agents having similar chemical and/or pharmacological properties, wherein the combinations maximize the therapeutic effect of the drug while minimizing their adverse effects. The methods and compositions of the invention are particularly useful in the treatment of obesity and related conditions which involves treating a subject with a sympathomimetic agent (e.g., phentermine or a phentermine-like drug) or bupropion in combination with an anti-epileptic agent (e.g., topiramate, zonisamide), CB1 antagonists (e.g., rimonabant), or a 5HT_2C-selective serotonin receptor agonist, (e.g., lorcaserin) for the treatment of obesity and related conditions. The invention also features kits for use in the practice of these novel therapies.

Claims

1. A composition for treating obesity or a related condition in a subject comprising:

a first pharmaceutical agent and a second pharmaceutical agent, wherein the second pharmaceutical agent is a sympathomimetic agent and wherein the first pharmaceutical agent is an anti-epileptic agent, CB1 receptor antagonist, or a 5HT_2C-selective serotonin receptor agonist.

2. The composition of claim 1, wherein said sympathomimetic agent is phentermine or bupropion.

3. The composition of claim 1, wherein said first pharmaceutical agent is an anti-epileptic agent.

4. The composition of claim 3, wherein said anti-epilpetic agent is selected from the group consisting of topiramate, zonisamide, γ

-vinyl GABA (vigabatrin), carbamazepine, clonazepam, ethosuximide, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenyloin, primidone, tiagabine, valproate, felbamate, oxazinane-dione, metharbital, ethotoin and mesantoin, vigabatrin, gabapentin, and oxcarbazepine.

5. The composition of claim 3, wherein said anti-epileptic agent is topiramate.

6. The composition of claim 3, wherein said anti-epileptic agent is zonisamide.

7. The composition of claim 1, wherein said first pharmaceutical agent is a CB1 receptor antagonist.

8. The composition of claim 7, wherein said CB1 receptor antagonist is selected from the group consisting of rimonabant, SLV-326, SLV-319, AM251, AM4113, AM281, Taranabant, NIDA-41020, NEWW 0327, O-2050, O-2654, CP-272871, CP-945598, CP-946598, AVE1625, Surinabant, LY320135, AVN-342, GRC-10389, Org-50189, PSNCBAM-1, E-6776, V-24343, ACPA, ACEA, HU-210, and HU-243.

9. The composition of claim 7, wherein said CB 1 receptor antagonist is rimonabant.

10. The composition of claim 1, wherein said first pharmaceutical agent is a 5HT_2C-selective serotonin receptor agonist.

11. The composition of claim 10, wherein said 5HT_2C-selective serotonin receptor agonist is selected from the group consisting of lorcaserin, mesulergine, agomelatine, fluoxetine, BVT933, DPCA37215, 1K264;

PNU 22394;

WAY161503, R-1065, and YM 348.

12. The composition of claim 10, wherein said 5HT_2C-selective serotonin receptor agonist is lorcaserin.

13. The composition of claim 1, comprising a dosage form comprising an immediate release form of the sympathomimetic agent and a controlled release form of the anti-epileptic agent, CB1 receptor antagonist, or 5HT_2C-selective serotonin receptor agonist.

14. The composition of claim 13, wherein the sympathomimetic agent is phentermine.

15. The composition of claim 13, wherein the sympathomimetic agent is bupropion.

16. The composition of claim 13, wherein the anti-epileptic agent is topiramate.

17. The composition of claim 13, wherein the anti-epileptic agent is zonisamide.

18. The composition of claim 13, wherein the CB1 receptor antagonist is rimonabant.

19. The composition of claim 13, wherein the 5HT_2C-selective serotonin receptor agonist is lorcaserin.

20. A method for treating obesity or a related condition in a subject comprising administering to the subject a first pharmaceutical agent and a second pharmaceutical agent, wherein the second pharmaceutical agent is a sympathomimetic agent and wherein the first pharmaceutical agent is an anti-epileptic agent, CB1 receptor antagonist, or a 5HT_2C-selective serotonin receptor agonist.

21. The method of claim 20, wherein the first pharmaceutical agent and the second pharmaceutical agent are administered separately.

22. The method of claim 21, wherein the first pharmaceutical agent and the second pharmaceutical agent are administered at different times of the day.

23. The method of claim 22, wherein the second pharmaceutical agent is administered in the morning and the first pharmaceutical agent is administered at least once later in the day.

24. The method of claim 23, wherein the second pharmaceutical agent is phentermine.

25. The method of claim 24, wherein the phentermine is an immediate release dosage form.

26. The method of claim 25, wherein the first pharmaceutical agent is topiramate.

27. The method of claim 25, wherein the first pharmaceutical agent is zonisamide.

28. The method of claim 25, wherein the first pharmaceutical agent is rimonabant.

29. The method of claim 25, wherein the first pharmaceutical agent is lorcaserin.

30. The method of claim 23, wherein the second pharmaceutical agent is bupropion.

31. The method of claim 30, wherein the bupropion is an immediate release dosage form.

32. The method of claim 31, wherein the first pharmaceutical agent is topiramate.

33. The method of claim 31, wherein the first pharmaceutical agent is zonisamide.

34. The method of claim 31, wherein the first pharmaceutical agent is rimonabant.

35. The method of claim 31, wherein the first pharmaceutical agent is lorcaserin.

36. The method of claim 20, wherein the condition is pre-diabetes, insulin-resistance or diabetes.

37. The method of claim 20, wherein the condition is hypertension.

38. The method of claim 20, wherein the condition is sleep apnea.

39. The method of claim 20, wherein the condition is nonalcoholic steatohepatitis.

40. The method of claim 20, wherein the condition is nonalcoholic fatty liver disease.

41. The method of claim 20, wherein the condition is diabetic nephropathy.

42. A kit comprising a packaged combination of a first pharmaceutical agent and a second pharmaceutical agent, wherein the second pharmaceutical agent is a sympathomimetic agent and wherein the first pharmaceutical agent is an anti-epileptic agent, CB1 receptor antagonist, or a 5HT_2C-selective serotonin receptor agonist and instructions for a patient to carry out drug administration to achieve weight loss, wherein the first and second pharmaceutical agents are present in separate and discrete dosage forms.

43. A kit comprising a sealed package of controlled release dosage forms each containing a first pharmaceutical agent and a second pharmaceutical agent, wherein the second pharmaceutical agent is a sympathomimetic agent and wherein the first pharmaceutical agent is an anti-epileptic agent, CB1 receptor antagonist, or a 5HT_2C-selective serotonin receptor agonist, wherein the dosage forms provide for immediate release of the second pharmaceutical agent and delayed release of the first pharmaceutical agent.