24 All patients provided written informed consent before undertaking any study-related procedures. This was a phase II, randomized, open-label trial of tegobuvir plus GS-9256, both administered orally in combination for 28 days, or check details both in combination with RBV, or both in combination with Peg-IFN alfa-2a and RBV. Patients were randomly assigned (1:1) to 40 mg of tegobuvir taken BID plus 75 mg of GS-9256 BID or 40 mg of tegobuvir BID plus 75 mg of GS-9256 BID plus RBV for 28 days. RBV (Copegus;

Roche, Nutley, NJ) was administered in a divided total daily oral dose of 1,000-1,200 mg (1,000 mg for patients weighing <75 kg and 1,200 mg for patients weighing ≥75 kg). Randomization was stratified by plasma HCV RNA level (< or ≥ 2,000,000 IU/mL) at screening (15 blocks of size 2). The sponsor's biometrics group generated the randomization schedule by using SAS software (SAS Institute Inc., Cary, NC). In assigning patients to treatment in this open-label study, individual study sites sent randomization

worksheets to the sponsor, BIBW2992 supplier who assigned subject numbers on the basis of the randomization schedule. After the first two treatment arms were completed, the protocol was amended and a third arm was added to the study to evaluate antiviral response with quadruple therapy. Patients received 40 mg of tegobuvir BID plus 75 mg of GS-9256 BID in combination with Peg-IFN alpha-2a (Pegasys; Roche) and RBV for 28 days. Subcutaneous injections of 180 μg of Peg-IFN alpha-2a were given once-weekly (QW). After the first 28 days of treatment, all patients received continued treatment with Peg-IFN

and RBV and were asked to return for follow-up visits 12, 24, 48, 上海皓元医药股份有限公司 and 72 weeks after the last study drug dose. The selection of the specific Peg-IFN (alpha-2a or alpha-2b) and RBV products and regimen during this phase of the study was at the discretion of the investigator. Peg-IFN and RBV standard of care was initiated earlier than 28 days in the following circumstances: lack of early response, as defined by a <2-log10 IU/mL HCV RNA reduction from baseline by day 5, or rebound, as defined by an HCV RNA increase of >0.5 log10 IU/mL from nadir confirmed over two time points occurring after day 5 with an absolute value >1,000 IU/mL. The study protocol (EudraCT identifier: 2009-013690-18) was approved by each institution’s independent ethics committee before study initiation. The primary efficacy endpoint was VL suppression at day 28, as measured by the proportion of patients achieving RVR, defined as plasma HCV RNA <25 IU/mL at day 28. Plasma HCV RNA reduction from baseline was also evaluated. Plasma for HCV RNA measurements was collected at screening, on day 1 predose (baseline), and on days 3, 5, 7, 14, 21, and 28.