Although the study was open-label, the sponsor was blinded to treatment allocation and viral load results until treatment week 12. Patients were enrolled at 51 centers in the United States. Patients were stratified by serum HCV RNA titers (≤780,000 IU/mL or >780,000 IU/mL) and baseline weight (≤75 or >75 kg). An interactive voice response system was used to randomize patients in a 1:1:1:1 ratio to receive weight-based TBV 20 mg/kg/day, 25 mg/kg/day, or 30 mg/kg/day (Valeant Pharmaceuticals North America, Aliso Viejo, CA) or weight-based RBV at 800, 1000, 1200, or 1400 mg/day (Copegus; Selleckchem Alectinib Hoffmann-La
Roche, Nutley, NJ) in combination with peg-IFN alfa 2b (PegIntron; Schering Corp., Kenilworth, NJ). All patients received doses twice
daily with their morning and evening meals. Patients were treated for 48 weeks, but treatment was discontinued for evidence of nonresponse defined as <2-log decline at week 12 or a positive viral load at week 24. Study treatment was initiated on day 1 and clinic visits occurred at treatment weeks (TWs) 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, and 48, as well as posttreatment follow-up weeks (FWs) 4, 12, 20, and 24. All patients who completed treatment with study drug or discontinued treatment prematurely (except nonresponders) immediately entered a 24-week follow-up period. The study protocol was approved by the institutional review boards of participating institutions and was conducted in accordance with the Declaration of Helsinki and provisions of Good Clinical Practices. All patients provided written Rapamycin chemical structure informed consent. The objective of this study was to select an optimal dose of TBV by comparing the efficacy and safety of three TBV dose levels MCE versus RBV based on body weight, both administered
with peg-IFN alfa-2b to therapy-naive compensated patients with genotype 1 chronic hepatitis C. The primary efficacy endpoint was early virologic response (EVR) defined as the proportion of patients with at least a 2-log decrease from baseline in serum HCV RNA levels at TW12. Additional efficacy endpoints assessed in the trial included SVR; undetectable HCV RNA at TW4, TW24, and TW48; and viral relapse for those who were responders at the end of treatment. Subgroup analyses were carried out to determine the impact of various baseline demographic factors such as sex, age, race, weight, baseline HCV RNA, and fibrosis score on response. Lack of efficacy was defined as less than a 2-log decrease of HCV RNA (IU/mL) at TW12 or detectable HCV RNA at TW24. Relapse rates were calculated by measuring the proportion of responding patients whose plasma HCV levels changed from undetectable at end of treatment to detectable at FW24. The primary safety endpoint was the proportion of patients with Hb < 10 g/dL at any time during the treatment period.