Statistical analysis
ADVERSE EVENTS
Statistical analysis was performed using SAS®9.4 (SAS Institute, Cary, NC, USA). Continuous data were summarized in terms of the mean and standard deviation (SD). Categorical variables were summarized in terms of frequency and percentages. The efficacy analysis was based on the full analysis set (FAS), and the safety analysis was based on the safety analysis set (SS), see in the supplementary information protocol.The primary efficacy analysis compared MADRS at Week 8 in the FAS using a mixed model for repeated measurements (MMRM) with the change from baseline in the MADRS total score at each time point after treatment as a dependent variable, baseline MADRS scale total scores as a covariate, baseline MADRS total score strata (26–34, ≥35), age strata (18–30, 31–40, 41–50, and 51–65 years), gender, and the group as fixed effects, and each fixed effect factor and the covariate were nested within each visit. The adjusted mean and its 95% confidence interval (CI) of the changes from baseline in MADRS scale total scores to week 8 in each group were calculated according to this model, as well as the difference and its 95% CI of the adjusted mean for the investigational drug 80 mg group, 160 mg group versus the placebo group.For safety analysis, the type, severity, frequency, and relationship with the study drug for all treat-emergent adverse events (TEAEs) were summarized, and subjects who dropped out from the study due to adverse events and those with serious adverse events were listed. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA). Shift tables were used to summarize the changes of clinical significance evaluation (based on the clinician’s evaluation) of laboratory parameters, and all abnormal parameters with clinical significance were listed.