Methods of Treating Obesity

• US 20080161279A1
• Filed: 12/21/2007
• Published: 07/03/2008
• Est. Priority Date: 12/21/2006
• Status: Abandoned Application

• Current Assignee: Aegerion Pharmaceuticals, Inc. (Valline Srl)
• Original Assignee: Aegerion Pharmaceuticals, Inc. (Valline Srl)
• Inventors: Wisler, Gerald L.
• Application Number:
  US11/962,383
• Publication Number:
  US 20080161279A1
• Time in Patent Office: Days
• US Class Current: 514/210.02
• 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 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention is directed to methods for treating and/or controlling obesity in a patient. The methods involve combination therapies using a microsomal triglyceride transfer protein (MTP) inhibitor (for example, AEGR-733 and implitapide) and a cholesterol absorption inhibitor (CAI) (for example, ezetimibe).

Claims

1. A method of treating and/or controlling obesity comprising administering to a patient in need thereof a MTP inhibitor in combination with a cholesterol absorption inhibitor.

2. The method of claim 1, wherein the patient is a human.

3. The method of claim 1 or 2, wherein the patient has a body mass index greater than or equal to about 30 kg/m² before the administration.

4. The method of claim 1 or 2, wherein the patient has a body mass index between about 30 kg/m² and about 60 kg/m² before the administration.

5. The method of claim 1, wherein the patient has a body mass index of between about 25 kg/m² and about 30 kg/m² before the administration.

6. The method of any one of claims 1-5, wherein the MTP inhibitor and the cholesterol absorption inhibitor are administered sequentially.

7. The method of any one of claims 1-5, wherein the MTP inhibitor and the cholesterol absorption inhibitor are administered substantially simultaneously.

8. The method of claims 6 or 7, wherein the MTP inhibitor and the cholesterol absorption inhibitor are administered in separate dosage forms.

9. The method of claim 7, wherein the MTP inhibitor and the cholesterol absorption inhibitor are administered as a single dosage form.

10. The method of any one of claims 1-9, wherein administering the MTP inhibitor in combination with a cholesterol absorption inhibitor provides a synergistic therapeutic effect.

11. The method of claim 10, wherein the MTP inhibitor is administered in a synergistically effective amount.

12. The method of claim 10 or 11, wherein the cholesterol absorption inhibitor is administered in a synergistically effective amount.

13. The method of any one of claims 1-12, wherein the cholesterol absorption inhibitor is selected from the group consisting of:

ezetimibe, MD-0727, FM-VP4, LPD84, LPD179, LPD 145 and AVE5530.

14. The method of any one of claims 1-13, wherein the cholesterol absorption inhibitor is ezetimibe.

15. The method of claim 14, wherein ezetimibe is administered at a dosage of about 1 to about 50 mg/day.

16. The method of claim 15, wherein ezetimibe is administered at a dosage of about 10 mg/day.

17. The method of any one of claims 1-16, wherein the MTP inhibitor is selected from at least one of:

AEGR-733, implitapide, JTT-130, CP-346086, and SLx-4090.

36. The method of any one of claims 1-35, wherein the incidence of gastrointestinal adverse events in the patient is less than 5%.

37. The method of any one of claims 1-35, wherein the method results in fewer incidences gastrointestinal adverse events in the patient as compared to administration of a MTP inhibitor alone.

38. The method of any one of claims 1-35, further comprising assessing a patient using a GSRS scale.

39. The method of claim 38, wherein the reported GSRS is between 1 and 2.

18. The method of 17, wherein the MTP inhibitor is selected from at least one of:

implitapide and AEGR-733.

19. The method of claim 18, wherein the MTP inhibitor is AEGR-733.

20. The method of claim 19, wherein AEGR-733 is administered at a dosage between about 1 to about 25 mg/day inclusive.

21. The method of claim 19, wherein AEGR-733 is administered at a dosage between about 20 mg/day and about 80 mg/day.

22. The method of claim 19, wherein AEGR-733 is administered at about 1 mg/day to about 12 mg/day.

23. The method of claim 22, wherein AEGR-733 is administered daily for at least twelve weeks.

24. The method of claim 22, wherein AEGR-733 is administered at 5 mg/day for at least four weeks.

25. The method of claim 19, comprising administering AEGR-733 at a first dosage of about 1 to about 7.5 mg/day for a first interval of at least four weeks.

26. The method of claim 25, wherein the first dosage is about 5 mg/day.

27. The method of claim 25, further comprising administering AEGR-733 at a second dosage of about 5 mg/day to about 12 mg/day for a second interval of at least four weeks.

28. The method of claim 27, wherein the second dosage is about 7.5 mg/day.

29. The method of claim 27 or 28, further comprising administering AEGR-733 at a third dosage of about 6 mg to about 15 mg/day for a third interval of at least four weeks.

30. The method of claim 29, wherein the third dosage is 10 mg/day.

31. The method of claim 18, wherein the MTP inhibitor is implitapide.

32. The method of claim 31, wherein implitapide is administered at a dosage between about 0.01 to about 60 mg/day inclusive.

33. The method of claim 32, wherein implitapide is administered at about 20 mg/day to about 40 mg/day.

34. The method of claim 33, wherein implitapide is administered daily for at least twelve weeks.

35. The method of claim 31, wherein implitapide is administered at about 20 mg/day to about 40 mg/day for at least four weeks.

40. A method of treating obesity comprising administering to a patient in need thereof a MTP inhibitor in combination with a cholesterol absorption inhibitor, wherein the administration of the combination results in a greater reduction in body mass of the patient after 12 weeks of daily administration as compared to 12 weeks of daily administration of a cholesterol absorption inhibitor or a MTP inhibitor alone.

41. A method of treating obesity comprising administering to a patient in need thereof a MTP inhibitor in combination with a cholesterol absorption inhibitor, wherein the administration of the combination results in a greater reduction in body mass of the patient after 12 weeks of daily administration as compared to 12 weeks of daily administration of a cholesterol absorption inhibitor or a MTP inhibitor alone, and wherein the method results in fewer incidences of gastrointestinal adverse events in the patient as compared to administration of a MTP inhibitor alone.

42. A method of inducing weight loss in a patient comprising administering to the patient an MTP inhibitor in combination with a cholesterol absorption inhibitor so as to induce weight loss in the patient.

43. The method of claim 42, wherein the weight loss is greater than that achieved by administering the cholesterol inhibitor alone or the MTP inhibitor alone.

44. The method of claim 42 or 43, wherein the weight loss is greater than the additive effect of administering the MTP inhibitor alone and the cholesterol absorption inhibitor alone.

45. The use of a combination of an MTP inhibitor and a cholesterol absorption inhibitor in the preparation of a medicament for the treatment of obesity.