Combination formulation of two antiviral compounds

Abstract

Disclosed are pharmaceutical compositions comprising Compound I, having the formula: and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.

1 .- 59 . (canceled) 
     
     
         60 . A method of treating hepatitis C in a human patient in need thereof comprising administering to the patient once daily a pharmaceutical composition, wherein the pharmaceutical composition comprises:
 a) about 200 mg of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound Ito copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula:   
       
         
           
           
               
               
           
         
         b) about 400 mg of substantially crystalline sofosbuvir having the formula: 
       
       
         
           
           
               
               
           
         
         c) about 355 mg of microcrystalline cellulose; 
         d) about 30 mg of croscarmellose sodium; and 
         e) about 15 mg of magnesium stearate. 
       
     
     
         61 . The method of  claim 60 , wherein the pharmaceutical composition is in the form of a tablet comprising a film coating. 
     
     
         62 . The method of  claim 61 , wherein the film coating is a polyvinylalcohol-based coating. 
     
     
         63 . The method of  claim 60 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1 and 12.7° 2θ±0.2. 
     
     
         64 . The method of  claim 60 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1, 20.1, and 20.8° 2θ±0.2. 
     
     
         65 . The method of  claim 60 , wherein the pharmaceutical composition is administered for about 12 weeks. 
     
     
         66 . The method of  claim 60 , wherein the patient is infected with hepatitis C virus of genotype 1. 
     
     
         67 . The method of  claim 60 , wherein the patient is infected with hepatitis C virus of genotype 2. 
     
     
         68 . The method of  claim 60 , wherein the patient is infected with hepatitis C virus of genotype 3. 
     
     
         69 . The method of  claim 60 , wherein the patient is infected with hepatitis C virus of genotype 4. 
     
     
         70 . The method of  claim 60 , wherein the patient is infected with hepatitis C virus of genotype 5. 
     
     
         71 . The method of  claim 60 , wherein the patient is infected with hepatitis C virus of genotype 6. 
     
     
         72 . The method of  claim 60 , wherein the patient is not suffering from cirrhosis.