Statistical analyses
zuranolone high‐dose, TEAEs
REGRESSION, EVENTS
The safety analysis population comprised all subjects who received at least one dose of the study drug. The PK concentration population comprised all subjects who reported at least one evaluable plasma concentration of zuranolone. The PK parameter population included all subjects with at least one appropriately estimated PK parameter. The EEG analysis population included all subjects who received at least one dose of zuranolone or placebo and had their EEG measured immediately before administration and at least at one time point after administration.The number of subjects and events of TEAEs and treatment‐related AEs were used to calculate the incidence of individual and overall AEs for each dose group. Laboratory tests, vital signs, ECG, C‐SSRS, SSS, MOAA/S, and DEQ‐5 results were described using summary statistics or a shift table. PK parameters were estimated using noncompartmental methods based on plasma zuranolone concentrations from all parts. For Part A, dose proportionality in Japanese healthy adults was evaluated by linear regression analysis using a power model. The dose independence in Japanese and White healthy adults, accumulation ratio in each group and PK difference at the same dose levels between Japanese and White healthy adults and between Japanese healthy adults and Japanese healthy elderly were compared using analysis of variance (ANOVA). For Part B, the effect of food on the PKs of zuranolone in Japanese healthy adults was evaluated using ANOVA, with subjects as a random effect and dietary condition (administration in the fasted or fed state), group, and dose timing as fixed effects.The estimated changes in low‐beta EEG power from the administration of zuranolone and placebo and their 95% confidence intervals (CIs) were calculated for each time point. Specifically, for the change from baseline of amplitude, differences between zuranolone high‐dose treatment and placebo treatment and their two‐sided 95% CIs, and between zuranolone low‐dose treatment and placebo treatment and their two‐sided 95% CIs were calculated in a 3‐period by 3‐treatment crossover ANOVA model using the subject as the block factor and period and treatment drug as main effects.No data imputation was performed during the statistical analysis, which was performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and WinNonlin version 6.2.1 (Certara, Princeton, NJ, USA).