Compositions of obeticholic acid and methods of use

Patent metadata

Field	Value
Publication number	US-10646499-B2
Application number	US-201816030141-A
Country	US
Kind code	B2
Filing date	Jul 9, 2018
Priority date	Apr 27, 2015
Publication date	May 12, 2020
Grant date	May 12, 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 nonalcoholic steatohepatitis (NASH) 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 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 25 mg.

3. The method of claim 1 , wherein the tablet comprises obeticholic acid.

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

5. The method of claim 4 , wherein the titration period comprises 1 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 25 mg, and the tablet is administered daily.

8. The method of claim 1 , wherein the amount is 10 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. A method of treatingnonalcoholic steatohepatitis (NASH) 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 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).

11. The method of claim 10 , wherein the amount is about 1 mg to about 25 mg.

12. The method of claim 10 , wherein the tablet comprises obeticholic acid.

13. The method of claim 10 wherein the starting dose is administered in a titration period.

14. The method of claim 13 , wherein said titration period comprises 1 to 6 months.

15. The method of claim 14 , wherein said titration period is 3 months or 6 months.

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

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

18. The method of claim 10 , wherein the amount is about 1 mg to about 5 mg, and the tablet is administered daily.

19. A method of treating nonalcoholic steatohepatitis (NASH) in a subject 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 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).

20. The method of claim 19 , wherein the amount is 25 mg, and the tablet is administered daily.

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

• A61K31/575 Primary

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• A61P1/16

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

• 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

• A61K45/06

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

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title