Efficacy Analysis
SECONDARY
The primary analysis was conducted on the intent-to-treat population and based on an ANCOVA model on the percentage change in LDL-C level from baseline to day 150 on each multiply imputed data set (100 total). The model included the part 1 treatment group as a fixed effect and the baseline LDL-C level as a covariate. Treatment effects from these 100 ANCOVA analyses were combined using the Rubin method.The key secondary end points were analyzed from a similar ANCOVA model using the same multiply-imputed washout model as the primary efficacy end point. For the other secondary end points, descriptive and graphical summaries by treatment group were presented. The mixed-effects model for repeated measures was performed to analyze other secondary end points, such as the absolute or percentage change from baseline over time up to day 180 for LDL-C, PCSK9, and other lipid levels. The model included fixed effects of the part 1 treatment group, visit (day 90, day 150, and day 180), baseline value, and the interaction between treatment and visit. The restricted maximum likelihood estimation approach was used with the covariance structure set as “unstructured.” The least squares means were calculated for each treatment at each visit, and linear combinations of the estimated least squares mean were used to form The analysis of the exploratory end point was similar to that of the primary end point. The post hoc analysis was conducted similar to that of the other secondary end points.All end points were tested using a 2-sided significance level of 0.05. The 