Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN α-2a/RBV in hepatitis C patients

Background & Aims Danoprevir (RG7227; ITMN-191) is a potent inhibitor of the HCV NS3/4A serine protease. The aims of this double-blind, placebo-controlled, multiple-ascending dose phase Ib study were to evaluate safety, tolerability, antiviral activity, resistance, and pharmacokinetics of once- and twice-daily danoprevir in the presence of low-dose ritonavir (danoprevir/r) and in combination with peginterferon alfa-2a (40KD)/ribavirin in treatment-naive HCV genotype 1 patients. Methods Thirty eligible patients were enrolled into three cohorts and treated with danoprevir/r or placebo/r all in combination with peginterferon alfa-2a (40KD)/ribavirin for 15 days. Cohort 1 received danoprevir/r at 100/100 mg twice daily; Cohort 2 200/100 mg once daily; and Cohort 3 200/100 mg twice daily. Results The median reductions in HCV RNA from baseline after 14 days of treatment (day 15) were –5.1, –4.8, and –4.6 log10 IU/ml in Cohorts 1, 2, and 3, respectively, and –2.7 log10 in placebo/r and peginterferon alfa-2a (40KD)/ribavirin recipients. Viral breakthrough was not observed in any patient. On day 15, HCV RNA was undetectable (