Statistical analysis
The sample size for this study was not prespecified; all participants who completed the RESTFUL study could enroll if they met the eligibility criteria. Efficacy endpoints were tested hierarchically until failure in the prespecified order listed above. Efficacy outcome measures were centrally assessed for the intent-to-treat population, which comprised all eligible participants who passed screening and were enrolled. Last observation carried forward imputation was used for all efficacy endpoints. For one-sample proportions (CGI-I and PGI-I responder rates for the treatment group), there was no appropriate reference value and thus 95% confidence intervals were presented instead of hypothesis testing. For all other endpoints, hierarchical hypothesis testing was employed to account for multiplicity. Mean scores were compared using The prespecified analysis described above evaluated the cross-sectional effect of TOMAC at week 24. It was also of interest to conduct exploratory analysis measuring the effect of TOMAC over the entire duration of treatment in the extension study based on repeated measures at weeks 8, 16, and 24 compared to week 0. Generalized linear models in SPSS version 29.0 were employed for repeated measures comparisons between treatment group and control group (to calculate treatment effect and treatment-time interaction) and between treatment group and baseline (to calculate time effect). A one-sided alpha level of 0.025 defined statistical significance for all comparisons.Differences in participant characteristics between treatment and control groups were evaluated using 