Study endpoints
SE, Movement Disorder, fracture, Parkinson’s Disease Rating Scale
MOVEMENT DISORDER
The adjusted mean (standard error) of the change from baseline in the MDS-UPDRS Part III total score at 24 weeks, the primary endpoint, was –4.4 (2.4) in the zonisamide add-on group and 2.0 (2.5) in the levodopa increase group (PP population) (A) Change from baseline in the MDS-UPDRS Part III total score at each time point for the zonisamide add-on group (•) and the levodopa increase group (▴) (PP population, by MMRM). Each point represents the adjusted mean with SE. B) Difference in change in MDS-UPDRS Part III total score at each time point between the zonisamide add-on group and the levodopa increase group (PP population, by MMRM). Each point represents the adjusted mean with 95% CI. The upper limit ≤3.0 (non-inferiority margin) indicated non-inferiority of zonisamide add-on group and an upper limit ≤0 indicated superiority. CI, confidence interval; MDS-UPDRS, The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale; MMRM, mixed model for repeated measure; PP, per-protocol; SE, standard error.The change from baseline in the MDS-UPDRS Part III total score at 16 weeks was –6.3 (1.8) in the zonisamide add-on group and –0.8 (2.0) in the levodopa increase group (PP population). The adjusted mean difference at 16 weeks was –5.5 (–10.9, –0.05). The upper limit of the 95% CI (–0.05) was lower than 0, which was the criterion for superiority of zonisamide add-on to the levodopa dose increase (The percentage of responders with ≥10%, ≥20%, and ≥30% change from baseline in the MDS-UPDRS Part III total score at 24 weeks was 44.0%, 28.0%, and 16.0% in the zonisamide add-on group and 36.4%, 18.2%, and 0% in the levodopa increase group (Percentage of responders in MDS-UPDRS Part III total score at 24 weeks (mITT population). MDS-UPDRS, The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale; mITT, modified intention-to-treat.For the MDS-UPDRS Part III sub-items, patients in the zonisamide add-on group showed significant improvement in speech (The mean (SD) at baseline and the mean change from baseline at 24 weeks in the MDS-UPDRS Part II total score were 17.0 (8.3) and –1.5 (5.1) in the zonisamide add-on group and 13.8 (7.7) and –0.8 (3.8) in the levodopa increase group, respectively (There were no significant differences in the mean changes between the two groups in RBDQ-JP, Eating Questionnaire, EQ-5D-5L, or ZBI total scores at any time point (Regarding the time from randomization to the first fall and first fracture (