Statistical analysis
SECONDARY
All participants who received at least one dose of study drug and had at least one postbaseline safety assessment were included in the safety analysis set for the assessment of safety variables. The full analysis set was defined as all participants to whom study treatment had been assigned at randomization and was used for summarizing demographic and baseline characteristics and assessment of efficacy variables. The end-of-study analysis was conducted on all participant data collected up to the end-of-study visit or the premature treatment discontinuation visit.Analyses were performed using SAS or R programming language. The primary variables were assessed using descriptive statistics (incidence of AEs and SAEs, overall and by preferred term) and baseline-adjusted mean estimates and pairwise differences with a 95% CI from a repeated measures (in the case of multiple assessments) analysis of covariance (ANCOVA) model (ALT, AST and relative change in % HFF). All LS means are reported by treatment arm and interpretation of the comparison does not include the 95% CI (of the difference) or Missing data for ALT and AST were accounted for by using repeated measures ANCOVA (mixed-effects model repeated measures; MMRM), assuming data were missing at random. In the case of dose reduction or treatment discontinuation, any ALT or AST assessments were set to ‘missing’ for all primary efficacy analyses. Missing data for % HFF were imputed using the baseline value for the week 12 analysis. No imputation was applied for the final analysis in Part C, where an MMRM model was used. In the case of treatment discontinuation, HFF assessments obtained >4 weeks after last treatment were set to ‘missing.’Analyses of secondary variables were also based on descriptive statistics, including change from baseline and pairwise differences versus placebo with 95% CI from repeated measures ANCOVA or pairwise ratio versus placebo with 95% CI from ANCOVA (ratio postdose versus predose for FGF19 and ratio postdose versus baseline for C4 at week 6 back-transformed from log scale). All LS means are reported by treatment arm and interpretation of the comparison does not include the 95% CI or All The primary objective of the study was to determine a safe dose or dose range. However, the assessment was to be made based on the whole safety profile and not on quantitatively formulated hypotheses for distinct parameters. Therefore, sample size was based on practicability with respect to expected speed of enrollment and duration of the study, and not on formal statistical criteria. The power considerations for efficacy assessment were based on the mean decrease from baseline in ALT seen with obeticholic acid versus placebo at week 12 (−28 (with an s.d. of 48) versus −11 (with an s.d. of 33), respectively)