Statistical analysis
fall injuries, fracture, fractures, fall-related injuries, BPSD
SECONDARY
The modified intention-to-treat (mITT) population was defined as all randomized patients who received at least one dose of the study drug and with available data on MDS-UPDRS Part III total score at baseline and after receiving study drugs. The per-protocol (PP) population was defined as all patients in the mITT population who complied with the study protocol. The safety population was defined as all patients enrolled in the study who received at least one dose of the study drug.The primary analysis for efficacy was performed in the PP population, and the secondary analysis for efficacy was conducted in the mITT population. To analyze the primary endpoint, a mixed model for repeated measures (MMRM) was used to estimate the difference in the adjusted means between the two groups, its 95% confidence interval (CI), and p-value. The MMRM included the change from baseline in MDS-UPDRS Part III total score at 8, 16, and 24 weeks in the PP population as a response variable, treatment group, evaluation time point (week), and treatment group– week interactions as fixed effects, and the value of MDS-UPDRS Part III total score at baseline as a covariate. In the MMRM analysis, an unstructured covariance was assumed for the intrasubject errors at the three time points. Non-inferiority was demonstrated when the upper limit of the two-sided 95% CI was ≤3.0 for the adjusted mean difference between the two groups in the change of MDS-UPDRS Part III total score from baseline at 24 weeks. Furthermore, if non-inferiority was demonstrated, superiority was demonstrated when the upper limit of the 95% CI was less than 0. A similar analysis to the primary analysis was performed for the change in MDS-UPDRS Part III total score from baseline to 8 and 16 weeks in the PP population. The same statistical analysis method was used for the secondary analysis of the primary endpoint in the mITT population.The secondary endpoints were analyzed in the mITT population. Regarding MDS-UPDRS Part II, RBDQ-JP, Eating Questionnaire, EQ-5D-5L, ZBI, Fall Questionnaire, NPI, MMSE, and pareidolia test, the statistical significance differences were tested by Wilcoxon signed-rank sum test for change from baseline and by Wilcoxon rank-sum test for intergroup differences. Time to first fall and first fracture, incidences of study discontinuation, and discontinuation due to worsening BPSD symptoms were estimated using the Kaplan– Meier Method, and these intergroup differences were tested by log-rank test. Intergroup differences in the percentages of responders in MDS-UPDRS Part III, proportion of patients with fall-related injuries, including fractures, due to falls at each time point, and proportions of patients undergoing surgical treatment for fall injuries were tested by Fisher’s exact test.AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRAversion 24.1). The number and percentage of patients in each treatment group who reported a TEAE and ADR were calculated and summarized by System Organ Class and Preferred Term.A 