Statistical analysis
SECONDARY
The primary objective of the study was to demonstrate superiority of SL-APO over SC-APO in improving motor function assessed as change from predose to 90 min postdose in MDS-UPDRS Part III score for SL-APO compared with SC-APO after 4 weeks of dosing in each crossover period (primary endpoint). The sample size calculation was based on randomization of 106 patients in the dose-optimization phase and ≥80 patients in the treatment phase, with ≥55 patients expected to complete treatment; this would provide 90% power to detect a mean treatment difference between SL-APO and SC-APO of 5.5 points for the change in MDS-UPDRS Part III score, assuming a standard deviation (SD) of 12 points for the period differences in treatment. The primary endpoint was analyzed in the treatment phase modified intention-to-treat (mITT) population (all patients who were randomized and received ≥1 dose of either study drug in the treatment phase) and was compared between treatment groups using a linear mixed model, with treatment group, visit week (0, 2, 4), treatment by visit week interaction, treatment phase sequence, and period as fixed factors and the week 0 visit predose MDS-UPDRS Part III score as a covariate. The primary and secondary endpoints were tested in a hierarchical order to maintain an overall type I error rate of 0.05. AEs were summarized descriptively for both the dose-optimization and treatment phase safety populations (all patients who received ≥1 dose of either study drug for each phase).