Statistical Analysis
SECONDARY, EVENT
A sample size of 202 participants, with 101 participants in each treatment arm, was determined to provide 90% power to detect a 30-meter difference between treatment groups in the 6MWT and a 90% power to detect a 1-unit difference in the PMMSA TFS. This was assuming standard deviations of 60 meters for 6MWT and 2 units for the PMMSA TFS, at an alpha level of 0.025, as established from a previous study of elamipretide in patients with PMM.Efficacy was assessed in the intention-to-treat (ITT) population, defined as all participants who received at least 1 dose of investigational medication, and the per-protocol (PP) population, which included all ITT participants without defined protocol violations/deviations identified per blinded data review before database lock. These protocol violations/deviations included not meeting inclusion/exclusion criteria or having a selected major protocol deviation deemed to potentially affect efficacy findings; not completing the study; not receiving investigational treatment within 2 days before the week 24 visit; having <80% compliance to investigational product; and not completing the study. Safety was assessed in the safety population, defined as all participants who received at least 1 dose of investigational medication.Primary and secondary efficacy outcomes were assessed as the change from baseline to each on-treatment time point with the primary time point being end of treatment (week 24). Analyses of continuous endpoints were conducted using a mixed-model repeated measures approach, with fixed effects for treatment, visit, the treatment-by-visit interaction, and participant as a random effect. The baseline value and a baseline-by-visit interaction for the endpoint were included as covariates. A family-wise alpha level of 0.05 was maintained for the primary endpoints, using Hochberg procedure at the primary time point of 24 weeks. If both primary endpoints were significantly different from placebo at the 0.05 (2-sided ) level of significance in favor of elamipretide, then both endpoints were considered statistically significant. If not, the endpoint with the smaller In the event that both endpoints in the primary endpoint family were significant at the 5% level, then secondary endpoints were to be tested at week 24 with type I error control, achieved by testing sequentially using a 2-sided alpha level of 0.05. The endpoints and hierarchy of comparisons were as follows: (1) change from baseline in Neuro-QoL Fatigue Short-Form (T score); (2) change from baseline in PGI of PMM symptoms; (3) change from baseline in CGI of PMM symptoms; and (4) change from baseline in most bothersome symptom score on the PMMSA. Sequential comparisons to control type I error were only to be completed if previous comparisons were statistically significant. For these analyses, 