Capsid assembly modulator dosing regimen

Abstract

The present disclosure is directed to methods of using a capsid assembly inhibitor for the treatment of hepatitis B virus infection.

1 - 30 . (canceled) 
     
     
         31 . A method of treating a hepatitis B virus (HBV) infection or a HBV-induced disease in a subject, comprising administering a pharmaceutical composition comprising
 (a) Compound A:   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, and 
         (b) a stabilizer; 
         wherein the amount of the compound (A) is 50-500 mg, and compound (A) is in the form of a spray dried powder. 
       
     
     
         32 . The method of  claim 31 , wherein the stabilizer is selected from at least one polymer chosen from the group consisting of HPMC, HPMC-AS, and HPMC E5. 
     
     
         33 . The method of  claim 32 , wherein said at least one polymer is in an amount of 50-1500 mg. 
     
     
         34 . The method of  claim 31 , wherein the composition comprises the compound (A) and stabilizer at a ratio in a range of 1:1 to 1:3 by weight. 
     
     
         35 . The method of  claim 31 , wherein the composition comprises 250 mg of Compound (A). 
     
     
         36 . The method of  claim 31 , wherein the composition comprises 50 mg of Compound (A). 
     
     
         37 . The method of  claim 31 , wherein the composition comprises 100 mg of Compound (A). 
     
     
         38 . The method of  claim 31 , wherein the composition further comprises microcrystalline cellulose and silicified microcrystalline cellulose. 
     
     
         39 . The method of  claim 31 , further comprising administering a transcription inhibitor. 
     
     
         40 . The method of  claim 39 , wherein the transcription inhibitor is a nucleoside analog. 
     
     
         41 . The method of  claim 40 , wherein the nucleoside analog is tenofovir disoproxil fumarate, tenofovir alafenamide, or entecavir monohydrate. 
     
     
         42 . The method of  claim 40 , wherein the nucleoside analog is tenofovir, or a pharmaceutically acceptable salt, or prodrug thereof. 
     
     
         43 . The method of  claim 42 , wherein the tenofovir is administered in an amount of 60-600 mg. 
     
     
         44 . The method of  claim 40 , wherein the nucleoside analog is entecavir, or a pharmaceutically acceptable salt thereof. 
     
     
         45 . The method of  claim 44 , wherein the entecavir is administered in an amount of 0.1-1 mg. 
     
     
         46 . The method of claim  1 , further comprising administering an immune modulator, or at least one siRNA or antisense oligonucleotide, or at least one Nucleic Acid Polymer, more particularly at least one immune modulator. 
     
     
         47 . The method of  claim 46 , the immune modulator is interferon. 
     
     
         48 . The method of  claim 31 , wherein the subject is HBV-treatment naïve. 
     
     
         49 . The method of  claim 31 , wherein the HBV-induced disease is cirrhosis, liver failure or hepatocellular carcinoma. 
     
     
         50 . A pharmaceutical composition comprising
 (a) Compound A:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, and
 (b) a stabilizer; 
 wherein the amount of the compound (A) is 50-500 mg, and compound (A) is in the form of a spray dried powder. 
 
     
     
         51 . The pharmaceutical composition of  claim 50 , wherein the stabilizer is selected from at least one polymer chosen from among HPMC and HPMC-AS. 
     
     
         52 . The pharmaceutical composition of  claim 51 , wherein said at least one polymer is in an amount of 50-1500 mg. 
     
     
         53 . The pharmaceutical composition of  claim 51 , wherein the composition comprises the compound (A) and stabilizer at a ratio of 1:3 by weight.