Statistical analysis
treatment-emergent adverse, fibrosis, steatohepatitis
FIBROSIS, SECONDARY, EVENTS, EVENTS, STEATOHEPATITIS
Summary tables are presented by treatment group and analysis visit (as applicable) using descriptive statistics. Continuous variables are summarized by arithmetic mean and SD unless otherwise stated. The number and percentage of patients in each category are presented for categorical variables for each treatment group and all patients (total).There were no prespecified hypotheses and statistical models in this study. The primary safety variables were analyzed descriptively using a summary table of absolute and relative frequencies, overall and by preferred term (for the occurrence of AEs, SAEs, and AEs leading to study discontinuation or dose reduction), and using a summary table of absolute and relative frequencies, overall and by type of AEs (for AESIs). Only treatment-emergent adverse events were considered for the analysis.Due to the nature of the primary objective, the assessment was made based on the whole safety profile and not on quantitatively formulated hypotheses for distinct parameters. Therefore, the sample size was based on the feasibility with respect to expected speed of enrollment and duration of the study.For power considerations, events with a true incidence of 30% and above are likely to be observed (almost 100% probability) in a group of 50 patients (size of each treatment group). Events with true incidences below 10% down to 3% are still very likely to be observed, while events with <50% probability are observed only if the true incidence is less than about 2.5%.For the secondary objectives, the difference in the proportion of patients on the different TXR plus CVC regimens who achieved at least a 1-point improvement in fibrosis stage and/or resolution of steatohepatitis at week 48 was compared with TXR and CVC monotherapy patients. Treatment differences between TXR + CVC combination therapy and monotherapy with TXR or CVC were evaluated using a Cochran-Mantel-Haenszel test that controlled for baseline fibrosis stage (F2/F3).For the PK analysis, dose-response and exposure-response relationships for TXR, CVC, and TXR + CVC combination therapy with key selected safety (eg, ALT and AST) and efficacy end points including biomarkers (eg, FGF19 and GGT) were explored.