The relative bioavailability was assessed by comparing the NVP XR and IR trough concentrations at week 24 and the geometric mean of all weeks. In determining the sample size, a planned noninferiority margin of 12% was selected for the difference in proportions between NVP XR and NVP IR in terms of continued virological response, assuming that 90% would be responders in both groups. A noninferiority test, with a one-sided α = 0.025 and a randomization ratio of 2:1 for the NVP XR and NVP IR treatment

arms, required 198 and 99 patients, respectively, in order to Selleckchem Oligomycin A have 90% power to reject the null hypothesis. The primary endpoint (proportion of patients with continued virological response at week 24) and its 95% confidence interval (CI) were estimated based on a time to loss of virological response (TLOVR) algorithm as specified by the US Food and Drug Administration (FDA) guidance [16]. Weighted treatment difference and corresponding variance were calculated Nutlin-3a nmr based on Cochran’s statistic [17] with continuity for variance calculation. Noninferiority to the control group in the primary endpoint was determined by comparing the lower 95% confidence limit of the difference in proportions of virological response for the two treatment arms (NVP XR vs. NVP IR) with the noninferiority margin of −12%. Because of the increased numbers of patients enrolled in this study, the noninferiority

margin for the study was adjusted to −10%. An additional approach (SNAPSHOT analysis) was also used to analyse the endpoint of continued suppression, as a key secondary analysis. In this approach, a patient with VL < 50 copies/mL at the 24-week time-point (± 4) was defined as a virological responder. The secondary endpoint of TLOVR using an LLOQ of <400 copies/mL was analysed using the Cox proportional hazard model with baseline background therapy as a stratum variable. All safety data were analysed using descriptive statistical methods. A total of 499 patients were enrolled in the study, an increase over the planned Etofibrate number of 300. This was a result of the unexpectedly rapid enrolment as a result of investigators pre-screening their patients. Of these, 445 were randomized, 295 to NVP XR and 148

to NVP IR; 54 patients were excluded primarily because they did not meet the eligibility criteria (Fig. 1). Two patients, one in each treatment group, were randomized but never received treatment, leaving 443 in the full analysis set. Baseline demographic data, which are shown in Table 1, were similar for the two treatment groups. The baseline VL value was defined as the mean of the VLs at screening and at randomization; 27 patients had a VL > 50 copies/mL at the randomization visit, so 6.1% of patients had a ‘detectable’ baseline VL. As the results for VL at randomization were not available until several days after randomization, these patients were still included in the study and continued in the study based on the earlier nondetectable screening of VL.