Compositions of obeticholic acid and methods of use

Patent metadata

Field	Value
Publication number	US-10758549-B2
Application number	US-202016787796-A
Country	US
Kind code	B2
Filing date	Feb 11, 2020
Priority date	Apr 27, 2015
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

The disclosure relates to obeticholic acid formulations with improved stability, dissolution, and/or solubility, methods of preparing the same for use and methods of treating various diseases and conditions.

First claim

The invention claimed is:

1. A method of treating primary biliary cholangitis (PBC) in a subject in need thereof, said method comprising administering to the subject a tablet comprising an intra-granular portion and an extra-granular portion, the intra-granular portion comprising obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof in an amount of about 1 mg to about 50 mg, and one or more pharmaceutically acceptable excipients, and the extra-granular portion comprising one or more pharmaceutically acceptable excipients,
wherein at least one pharmaceutically acceptable excipient in the tablet has an alcohol content of less than about 6% (w/w);
wherein the amount is a starting dose, an adjusted dose or a re-adjusted dose; and
wherein the tablet is administered daily (QD), every other day (Q2D), once a week (QW), twice a week (BID), three times a week (TIW), once a month (QM), or twice a month (Q2M).

2. The method of claim 1 , wherein the amount is about 1 mg to about 10 mg.

3. The method of claim 1 , wherein the intra-granular portion comprises obeticholic acid.

4. The method of claim 1 , wherein the amount is a starting dose and the tablet is administered in a titration period.

5. The method of claim 4 , wherein the titration period is from 1 month to 6 months.

6. The method of claim 5 , wherein the titration period is 3 months or 6 months.

7. The method of claim 1 , wherein the amount is 10 mg, and the tablet is administered daily.

8. The method of claim 1 , wherein the amount is 5 mg, and the tablet is administered daily.

9. The method of claim 1 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.

10. The method of claim 1 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours before the tablet is administered.

11. The method of claim 1 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours after the tablet is administered.

12. A method of treating primary biliary cholangitis (PBC) in a subject in need thereof, said method comprising administering to the subject a tablet comprising obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof in an amount of about 1 mg to about 50 mg, and one or more pharmaceutically acceptable excipients,
wherein the obeticholic acid or the pharmaceutically acceptable salt or amino acid conjugate thereof is in the form of jet-milled particles, and wherein at least 50% of the particles have a diameter of 200 μm or less;
wherein at least one pharmaceutically acceptable excipient in the tablet has an alcohol content of less than about 6% (w/w);
wherein the amount is a starting dose, an adjusted dose or a re-adjusted dose; and
wherein the tablet is administered daily (QD), every other day (Q2D), once a week (QW), twice a week (BID), three times a week (TIW), once a month (QM), or twice a month (Q2M).

13. The method of claim 12 , wherein the amount is about 1 mg to about 10 mg.

14. The method of claim 12 , wherein the tablet comprises obeticholic acid.

15. The method of claim 12 , wherein the amount is a starting dose and the tablet is administered in a titration period.

16. The method of claim 15 , wherein the titration period is from 1 month to 6 months.

17. The method of claim 16 , wherein the titration period is 3 months or 6 months.

18. The method of claim 12 , wherein the amount is 10 mg, and the tablet is administered daily.

19. The method of claim 12 , wherein the amount is 5 mg, and the tablet is administered daily.

20. The method of claim 12 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.

21. The method of claim 12 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours before the tablet is administered.

22. The method of claim 12 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours after the tablet is administered.

23. A method of treating primary biliary cholangitis (PBC) in a subject in need thereof, said method comprising administering to the subject a tablet comprising an intra-granular portion and an extra-granular portion, the intra-granular portion comprising obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof in an amount of about 1 mg to about 50 mg, and one or more pharmaceutically acceptable excipients, and the extra-granular portion comprising one or more pharmaceutically acceptable excipients,
wherein the obeticholic acid or the pharmaceutically acceptable salt or amino acid conjugate thereof is in the form of jet-milled particles, and wherein at least 50% of the particles have a diameter of 200 μm or less;
wherein at least one pharmaceutically acceptable excipient in the tablet has an alcohol content of less than about 6% (w/w);
wherein the amount is a starting dose, an adjusted dose or a re-adjusted dose; and
wherein the tablet is administered daily (QD), every other day (Q2D), once a week (QW), twice a week (BID), three times a week (TIW), once a month (QM), or twice a month (Q2M).

24. The method of claim 23 , wherein the intra-granular portion comprises obeticholic acid.

25. The method of claim 24 , wherein the amount is 10 mg, and the tablet is administered daily.

26. The method of claim 24 , wherein the amount is 5 mg, and the tablet is administered daily.

27. The method of claim 24 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.

28. The method of claim 24 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours before the tablet is administered.

29. The method of claim 24 , wherein the method further comprises administering to the subject a bile acid binding resin at least 4 hours after the tablet is administered.

30. The method of claim 23 , wherein the amount is about 1 mg to about 10 mg.

31. The method of claim 23 , wherein the amount is a starting dose and the tablet is administered in a titration period.

32. The method of claim 31 , wherein the titration period is from 1 month to 6 months.

33. The method of claim 32 , wherein the titration period is 3 months or 6 months.

Assignees

• Intercept Pharmaceuticals Inc
• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Lancaster Richard Gail
• Olmstead Kay K
• Kagihiro Masashi
• Matono Mitsuhiro
• Taoka Ikuko
• Pruzanski Mark
• Shapiro David
• Hooshmand-Rad Roya
• Pencek Richard
• Sciacca Cathi
• Eliot Lise
• Edwards Jeffrey
• Macconell Leigh A
• Marmon Tonya K

Classifications

• C07J9/005

  containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K47/50

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title