bms-790052 and Diarrhea

Patients with chronic hepatitis C virus (HCV) infection and previous null response to pegylated interferon (Peg-IFN) and ribavirin (RBV) have limited therapeutic options. HCV genotype 1 is the most common worldwide and the most difficult to treat; genotype 1b is the most common subtype of genotype 1 outside North America. The enhanced antiviral activity achieved by combining two direct-acting antiviral (DAA) agents may improve clinical outcomes. This open-label, phase IIa study included 10 patients with chronic HCV genotype 1b infection and previous null response (<2 log(10) reduction in HCV RNA after 12 weeks) to Peg-IFN and RBV. Patients received dual DAA treatment for 24 weeks with the nonstructural protein 5A replication complex inhibitor, daclatasvir (60 mg once-daily), and the nonstructural protein 3 protease inhibitor, asunaprevir (initially 600 mg twice-daily, then subsequently reduced to 200 mg twice-daily). The primary efficacy endpoint was the proportion of patients with sustained virologic response (SVR) at 12 weeks post-treatment (SVR(12) ). Nine patients completed 24 weeks of treatment; 1 patient discontinued treatment after 2 weeks. In the 9 patients who completed the full course of treatment, HCV RNA was undetectable at week 8 and remained undetectable through the end of treatment; all 9 patients achieved SVR(12) and SVR(24) . HCV RNA also remained undetectable post-treatment in the patient who discontinued after 2 weeks. There was no viral breakthrough. Diarrhea and headache, generally mild, were the most common adverse events; transaminase elevations were reported in 3 patients, but did not result in discontinuation.. Dual therapy with daclatasvir and asunaprevir, without Peg-IFN and RBV, can achieve high SVR rates in difficult-to-treat patients with HCV genotype 1b infection and previous null response to Peg-IFN and RBV.

Topics: Adult; Aged; Antiviral Agents; Carbamates; Diarrhea; Drug Therapy, Combination; Female; Genotype; Headache; Hepacivirus; Hepatitis C; Humans; Imidazoles; Incidence; Interferon-alpha; Isoquinolines; Japan; Male; Middle Aged; Polyethylene Glycols; Protease Inhibitors; Pyrrolidines; Recombinant Proteins; Ribavirin; Sulfonamides; Treatment Failure; Treatment Outcome; Valine; Viral Nonstructural Proteins