Statistical analysis
weight loss
SECONDARY
The sample size of 240 participants was estimated to provide at least 95% power to show the superiority of optimal mazdutide dose to placebo in terms of body weight change from baseline to week 24, at a two-sided significance level of 0.05. In the calculation of the sample size, it was assumed the mean percentage change in body weight from baseline to week 24 of 2.3% with placebo and −10% with optimal mazdutide dose, a common standard deviation of approximately 8%, and a dropout rate of 20%.The efficacy endpoints were evaluated in mITT population, defined as all participants who received at least one dose of the study treatment and had both baseline and post-baseline body weight measurements. The safety endpoints were evaluated in the safety population, defined as all participants who received at least one dose of the study treatment.The primary analysis for the primary endpoint was done using ANCOVA model with treatment and stratification factor as fixed effects and the baseline body weight value as a covariate. Missing data at week 24 were imputed using last observation carried forward method. Treatment difference versus placebo were provided, with 95% CI and Continuous secondary efficacy endpoints were analysed using MMRM as the sensitivity analysis for the primary endpoint, with corresponding baseline values as covariates. For categorical secondary endpoints of body weight loss of 5% or more and 10% or more at week 24, Clopper-Pearson method was used for within-group CI calculation and Mantel-Haenszel method was used for between-group CI calculation. Cochran-Mantel-Haenszel method was used for statistical testing. Participants without week 24 body weight assessment were treated as non-responders. Post-hoc analysis of participant with body weight loss of 15% or more at week 24 was done using same method above.Safety data were summarised descriptively.All statistical analyses were done using SAS version 9.4. This study is registered with ClinicalTrials.gov, number NCT04904913.