Compositions and methods for treating hepatitis C virus

• US 9,549,941 B2
• Filed: 11/11/2014
• Issued: 01/24/2017
• Est. Priority Date: 11/29/2011
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Cleary, Darryl G., Reynolds, Charles J., Berrey, Miriam Michelle, Hindes, Robert G., Symonds, William T., Ray, Adrian S., Mo, Hongmei, Hebner, Christy M., Oliyai, Reza, Zia, Vahid, Stefanidis, Dimitrios, Pakdaman, Rowchanak, Casteel, Melissa Jean
• Primary Examiner(s): Arnold, Ernst V
• Assistant Examiner(s): Chang, Kyung Sook
• Application Number:
  US14/538,736
• Publication Number:
  US 20150150896A1
• Time in Patent Office: 805 Days
• Field of Search: None
• US Class Current: 1/1
• 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 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/664 Amides of phosphorus acids
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

Disclosed herein are a composition and unit dosage form for the treatment of hepatitis C virus (HCV) infection comprising GS-7977 and at least one pharmaceutically acceptable excipient, as well as methods for making said composition and unit dosage form. Also disclosed herein is a method of treating a subject, preferably a human, infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period.

Claims

1. A method of treating a human infected with hepatitis C virus comprising administering to the human a composition comprising:

a) about 25% to about 35% w/w of a crystalline compound having the structure;

2. The method according to claim 1, wherein the method comprises administering a daily dose of about 400 mg of the crystalline compound.

3. The method according to claim 2, wherein the method comprises administering a daily dose of about 1000 mg to about 1200 mg of ribavirin.

4. The method according to claim 1, wherein the method comprises administering the crystalline compound to the human once, twice, three times or four times daily.

5. The method according to claim 1, wherein the method comprises administering ribavirin to the human once, twice, three times or four times daily.

6. The method according to claim 1, wherein the method comprises administering the crystalline compound to the human once daily.

7. The method according to claim 6, wherein the method comprises administering ribavirin to the human twice daily.

8. The method according to claim 1, wherein the method comprises administering a daily dose of about 400 mg of the crystalline compound and a daily dose of about 1000 mg to about 1200 mg of ribavirin.

9. The method according to claim 8, wherein the method comprises administering the crystalline compound to the human once daily and administering ribavirin to the human twice daily.

10. The method of claim 1, wherein the method comprises administering the crystalline compound and ribavirin to the human concurrently or alternatively.

11. The method of claim 1, wherein the method comprises administering the crystalline compound and ribavirin to the human orally.

12. The method of claim 11, wherein the method comprises administering the crystalline compound in a tablet or a capsule form.

13. The method of claim 12, wherein the method comprises administering ribavirin in a tablet or capsule form.

14. The method of claim 1, wherein the human is infected with hepatitis C virus genotype 1, 2, 3, 4, 5, or 6, or any combination thereof.

15. The method of claim 1, wherein the human is infected with hepatitis C virus genotype 2 or 3.

16. The method of claim 1, wherein the method comprises administering the composition in combination with ribavirin for a period of about 12 weeks.

17. The method of claim 1, wherein the composition further comprises:

about 2.5% w/w to about 7.5% w/w of a disintegrant;

about 0.25% w/w to about 0.75% w/w of a glidant; and

about 1.25% w/w to about 1.75% w/w of a lubricant.

18. The method of claim 1, wherein the diluent consists of about 30% w/w of mannitol and about 30% w/w of microcrystalline cellulose.

19. The method of claim 1, wherein the composition comprises about 33% w/w of the crystalline compound.

20. A method of treating a human infected with hepatitis C virus comprising administering to the human a composition comprising:

about 25% w/w to about 35% w/w of a crystalline compound having the structure;

21. The method of claim 20, wherein the composition comprises:

about 33% w/w of the crystalline compound;

about 30% w/w of mannitol;

about 30% w/w of microcrystalline cellulose;

about 5% w/w of croscarmellose sodium;

about 0.5% w/w of colloidal silicon dioxide; and

about 1.5% w/w of magnesium stearate.

22. The method of claim 20, wherein the composition comprises an intragranular portion comprising:

about 33% w/w of the crystalline compound;

about 30% w/w of mannitol;

about 25% w/w of microcrystalline cellulose;

about 2.5% w/w of croscarmellose sodium;

about 0.45% w/w of colloidal silicon dioxide; and

about 0.75% w/w of magnesium stearate.

23. The method of claim 20, wherein the composition further comprises an extragranular portion comprising:

about 5% w/w of microcrystalline cellulose;

about 2.5% w/w of croscarmellose sodium;

about 0.05% w/w of colloidal silicon dioxide; and

about 0.75% w/w of magnesium stearate.