Compositions and methods for treating hepatitis c virus

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.

1 . A pharmaceutical composition comprising:
 a) about 25% to about 35% w/w of GS-7977; and   b) at least one pharmaceutically acceptable excipient.   
     
     
         2 . The composition according to  claim 1 , wherein the composition comprises about 30% to about 35% w/w of GS-7977. 
     
     
         3 . The composition according to  claim 1 , wherein the composition comprises about 30% w/w of GS-7977. 
     
     
         4 . The composition according to  claim 1 , wherein the composition comprises about 33% w/w of GS-7977. 
     
     
         5 . The composition according to  claim 1 , wherein the composition comprises crystalline GS-7977. 
     
     
         6 . The composition according to  claim 5 , wherein the crystalline GS-7977 has XRPD 2θ-reflections (°) at about:
 (1) 5.2, 7.5, 9.6, 16.7, 18.3, and 22.2; 
 (2) 5.0, 7.3, 9.4, and 18.1; 
 (3) 4.9, 6.9, 9.8, 19.8, 20.6, 24.7, and 26.1; 
 (4) 6.9, 9.8, 19.7, 20.6, and 24.6; 
 (5) 5.0, 6.8, 19.9, 20.6, 20.9, and 24.9; 
 (6) 5.2, 6.6, 7.1, 15.7, 19.1, and 25.0; or 
 (7) 6.1, 8.2, 10.4, 12.7, 17.2, 17.7, 18.0, 18.8, 19.4, 19.8, 20.1, 20.8, 21.8, and 23.3. 
 
     
     
         7 . The composition according to  claim 6 , wherein the crystalline GS-7977 has XRPD 2θ-reflections (°) at about:
 (1) 5.0, 7.3, 9.4, and 18.1; or 
 (2) 6.1, 8.2, 10.4, 12.7, 17.2, 17.7, 18.0, 18.8, 19.4, 19.8, 20.1, 20.8, 21.8, and 23.3. 
 
     
     
         8 . The composition according to  claim 5 , wherein the crystalline GS-7977 has XRPD 2θ-reflections (°) at about:
 (1) 5.0 and 7.3; or 
 (2) 6.1 and 12.7. 
 
     
     
         9 . The composition according to  claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises at least one of a diluent, a disintegrant, a glidant, and a lubricant. 
     
     
         10 . The composition according to  claim 9 , wherein the at least one pharmaceutically acceptable excipient comprises a diluent selected from the group consisting of dicalcium phosphate, cellulose, compressible sugars, dibasic calcium phosphate dehydrate, lactose, mannitol, microcrystalline cellulose, starch, tribasic calcium phosphate, and combinations thereof. 
     
     
         11 . The composition according to  claim 10 , wherein the diluent is selected from the group consisting of mannitol, microcrystalline cellulose, and combinations thereof. 
     
     
         12 . The composition according to  claim 9 , wherein the at least one pharmaceutically acceptable excipient comprises a disintegrant selected from the group consisting of croscarmellose sodium, crospovidone, microcrystalline cellulose, modified corn starch, povidone, pregelatinized starch, sodium starch glycolate, and combinations thereof. 
     
     
         13 . The composition according to  claim 12 , wherein the disintegrant is croscarmellose sodium. 
     
     
         14 . The composition according to  claim 9 , wherein the at least one pharmaceutically acceptable excipient comprises a glidant selected from the group consisting of colloidal silicon dioxide, talc, starch, starch derivatives, and combinations thereof. 
     
     
         15 . The composition according to  claim 14 , wherein the glidant is colloidal silicon dioxide. 
     
     
         16 . The composition according to  claim 9 , wherein the at least one pharmaceutically acceptable excipient comprises a lubricant selected from the group consisting of calcium stearate, magnesium stearate, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, and combinations thereof. 
     
     
         17 . The composition according to  claim 16 , wherein the lubricant is magnesium stearate. 
     
     
         18 . The composition according to  claim 1  further comprising a coating agent. 
     
     
         19 . The composition according to  claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises:
 a) about 55% w/w to about 65% w/w of a diluent;   b) about 2.5% w/w to about 7.5% w/w of a disintegrant;   c) about 0.25% w/w to about 0.75% w/w of a glidant; and   d) about 1.25% w/w to about 1.75% w/w of a lubricant.   
     
     
         20 . The composition according to  claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises:
 a) about 30% w/w of mannitol and about 30% w/w of microcrystalline cellulose;   b) about 5% w/w of croscarmellose sodium;   c) about 0.5% w/w of colloidal silicon dioxide; and   d) about 1.5% w/w of magnesium stearate.   
     
     
         21 - 50 . (canceled)