Compositions and methods for treating hepatitis C virus
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.
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:
and
b) about 55% w/w to about 65% w/w of a diluent consisting of mannitol and microcrystalline cellulose,
in combination with a daily dose of about 800 mg to about 1200 mg ribavirin,
wherein the crystalline compound has XRPD 2θ-reflections)(°) at about: 6.1 and 12.7.
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:
about 30% w/w of mannitol;
about 30% w/w of microcrystalline cellulose;
about 2.5% w/w to about 7.5% w/w of croscarmellose sodium;
about 0.25% w/w to about 0.75% w/w of colloidal silicon dioxide; and
about 1.25% w/w to about 1.75% w/w of magnesium stearate,
in combination with a daily dose of about 800 mg to about 1200 mg ribavirin, wherein the crystalline compound has XRPD 2θ-reflections)(±0.2°) at about 6.1 and 12.7.
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.