Of the 10 protocol-defined failures identified in the study, postbaseline resistance testing was not performed in 5 patients because of low HCV RNA levels (<1,000 IU/mL by day 42 of the study). Of the remaining 5

EPZ-6438 cell line patients, 2 genotype 1b–infected patients (ANs 2957 and 3290) receiving placebo did not exhibit a greater than 2log10 decrease in HCV RNA during the dosing period (classified as “nonresponders”). RAVs were not detected in viruses from these patients by population sequencing (Table 4). The R155K variant was detected in viruses from 1 genotype 1a–infected patient (AN 3249), who exhibited a greater than 1log10 increase from nadir while receiving vaniprevir 800 mg QD (classified as a “breakthrough”) (Fig. 3). Two patients (1 infected with genotype 1a and 1 with genotype 1b) who received vaniprevir 300 mg BID exhibited a greater than 1log10 increase in HCV RNA from nadir after

completion of the 28-day vaniprevir dosing period (classified as “relapse after vaniprevir/placebo Alvelestat supplier dosing”). RAVs R155K and D168V were detected by population sequencing in the genotype 1a–infected patient (AN 3242; Table 4). Clonal analysis revealed that these RAVs were not linked (data on file; Merck & Co., Inc., Whitehouse Station, NJ). RAVs D168V and D168T were identified in viruses from the genotype 1b–infected patient (AN 2966). In total, 70 patients provided consent Cytidine deaminase for inclusion in the host genetic analysis, but 3 samples had insufficient template. The IL28B genotype analysis therefore compared genotype at loci rs12979860, rs12980275, and rs8103142 with RVR and SVR outcomes in 67 patients with samples available for testing from all treatment groups. IL28B genotype did not correlate significantly with SVR outcome (Supporting Table 3 and data not shown; P = 0.486 for rs12979860), in contrast to previous published work on response to Peg-IFN-α-2a/RBV treatment in a larger cohort of patients.19 IL28B genotype also did not associate

with the primary endpoint for this study, RVR (Supporting Table 4 and data not shown; P = 0.312 for rs12979860). In total, AEs were reported by 85 (90.4%) of the 94 treated patients across all treatment groups, with no notable between-group differences (Table 5). Among patients receiving vaniprevir, nausea (34.7%), headache (33.3%), influenza-like illness (22.7%), and fatigue (21.3%) were the most frequently reported AEs. These incidence rates were generally comparable with those among patients in the placebo group: nausea (26.3%), headache (36.8%), influenza-like illness (21.1%), and fatigue (36.8%). However, vomiting was reported by 40.0% (8 of 20) of the patients in the vaniprevir 600-mg BID group, compared to 0% (0 of 19) of the patients in the placebo group, and the difference of 40.0% (95% CI: 19.9%-61.