Investigators recorded all observed or volunteered adverse events (AEs), as well as the severity (mild, moderate, severe) and the

investigator’s opinion of the relationship to study treatment. The AEs included adverse drug reactions, illnesses with onset during the study, and exacerbation of previous illnesses. In addition, the investigator recorded as AEs any clinically significant changes in physical examination findings and abnormal objective test findings (e.g., electrocardiogram results, laboratory test results, check details and so forth). The AEs were monitored throughout the study, and coded using MEdDRA version 11.0. Baseline HCV RNA was defined as the average of screening and day 0 and 1 (0 hour) values. In study 1, data for patients receiving placebo across all

cohorts and data for the two HCV subtypes were pooled for analysis. Change in log10 HCV RNA between baseline and day 8 and maximum change from baseline were secondary endpoints. In study 2, change in log10 HCV RNA between baseline and the last day of dosing, and maximum change from baseline, were coprimary endpoints. Statistical analyses were conducted at a two-sided 5% significance level. Descriptive statistics were used to summarize AEs. HCV genotype was determined with the Versant HCV genotype assay, version 2.0 (LiPA; Bayer HealthCare Diagnostics, Tarrytown, NY) and confirmed AZD5363 mouse retrospectively for all patients using phylogenetic analysis of NS5B nucleotide sequence at baseline (Lab21 Healthcare, Cambridge, UK). Genotype

designations indicated in Table 1 are derived from retrospective phylogenetic analysis. Two-step amplification and population sequencing of the HCV NS5B encoding selleck inhibitor region was performed on plasma samples collected at: screening and days 8 and 28 in study 1; at baseline and days 5, 10, and 28 for cohort A; and baseline and days 3, 5, and 28 for cohort B in study 2. The derived translations were aligned to reference sequences according to genotype: genotype 1a (Genbank accession, H77: NC_004102) and genotype 1b (Genbank accession, Con1: AJ238799). All 32 randomized patients in study 1 and all 20 patients in study 2 completed the studies. In study 1, there were no notable differences in demographic parameters or baseline HCV RNA concentrations between patients receiving filibuvir or placebo (Table 1). Demographics and baseline plasma HCV RNA concentrations were similar between studies 1 and 2. The genotypic distribution (1a versus 1b) within each cohort is listed in Table 1. Administration of filibuvir resulted in rapid, dose-dependent reductions in HCV RNA concentrations (Fig. 2). The mean maximum change from baseline in HCV RNA ranged from −0.97 log10 IU/mL (100 mg BID) to −2.30 log10 IU/mL (700 mg BID; Table 2). No patient achieved undetectable HCV RNA levels during filibuvir therapy. In study 1, the mean maximum reductions in HCV RNA concentrations were statistically greater compared with placebo (P < 0.