5%, and giving a final noninferiority margin of 11%. A sample size of 704 patients, including 352 patients in each treatment group, was considered sufficient for showing noninferiority of TVR twice-daily dosing. Assuming an expected SVR12 rate of 72% in each group and a noninferiority margin of –11%, this sample size provided 90% power to reject the inferiority hypothesis. Secondary efficacy variables included the proportion of patients who achieved RVR, achieved SVR at week 24, experienced a relapse, and experienced on-treatment virological failure. For virological responses, data were analyzed without imputation (“observed” analyses) and using a noncompleter equals failure (NC = F) imputation.
Intermittent missing values were imputed as a “response” if the immediate preceding and following visits showed a response and as “no response” otherwise. If any study drug was prematurely discontinued buy H 89 due to virological failure, “no response” was imputed. If any study drug was prematurely discontinued for another reason (ie, not related to virological failure), missing data were marked as “missing for another reason.” However, missing HCV RNA assessments at the SVR12 visit were not imputed and were considered treatment failures (no SVR). Additional sensitivity analyses were also performed to compare virological response rates (Supplementary
Methods). Descriptive statistics of treatment adherence and the number of patients in each adherence category were reported for TVR Alectinib in vitro dosing frequency, timing of intake,
and intake based on the e-diary. This diary captured the amount and timing of TVR dosing relative to the prescribed regimen. Additionally, adherence to dosing of TVR and DNA ligase PEG-IFN/RBV was measured by dispensed versus returned medications (pill count). Adherence was expressed as the percentage of prescribed doses during the treatment period and categorized by defined thresholds. The e-diary analysis was performed using the ITT population, with missing entries considered 0% adherent. Observed data analyses were also performed. The 95% CIs stated in the report were part of the prespecified statistical analysis and provided an informal comparison within the framework of noninferiority. P values stated in the report for the secondary efficacy variables and subgroup analyses were from post hoc statistical testing. HCV NS3/4A population sequencing was performed on plasma samples at baseline and in the case of virological failure or relapse. The frequency of TVR-resistant variants is presented descriptively. Individual empirical Bayesian estimates of TVR PK parameters were determined using a population PK modeling approach. Blood samples (sparse sampling) were taken at sites with the capabilities for PK sampling at weeks 2, 4, 6, and 8 to determine concentrations of TVR, PEG-IFN, and RBV for adherence assessments as well as for PK evaluations.