Objective: To characterize the efficacy of zonisamide in improving motor symptoms, we performed a post-hoc analysis using data from a phase 3 study that evaluated the efficacy of zonisamide (administered for 12 weeks) on parkinsonism in dementia with Lewy bodies (DLB).

Background: Zonisamide, widely used for epilepsy, has been available as an anti-Parkinson drug in Japan since 2009 [1]. We conducted a phase 2 [2], and phase 3 studies to evaluate the efficacy for parkinsonism and safety in patients with DLB and showed zonisamide improved overall parkinsonism (Unified Parkinson’s Disease Rating Scale [UPDRS] Part 3 total score) and well-tolerated.

Methods: Among the motor symptoms, we focused on tremor (UPDRS items 20 and 21), rigidity (UPDRS item 22), bradykinesia (UPDRS items 23, 24, 25, 26 and 31), and gait/postural instability (UPDRS items 29 and 30). For each of these symptoms, the change in the score from baseline at final evaluation (Week 12) was analyzed using the mixed-effect model for repeated measures (MMRM), among the patients who had the symptom at least once in any evaluation point extracted from the efficacy analysis set (modified intention-to-treat [mITT] population) (n=346, consisting of 118 given placebo, 117 given zonisamide 25 mg, and 111 given zonisamide 50 mg) of the phase 3 study.

Results: At baseline, bradykinesia was the most common of the selected four symptoms in the patients enrolled in this study, accounting for a major part of the UPDRS Part 3 total score [Table 1]. At final evaluation, the changes in the scores from baseline were greater with zonisamide than with placebo for all of the four symptoms, with significant improvement particularly for bradykinesia and tremor.

Conclusions: This post-hoc analysis indicated that zonisamide is particularly effective on bradykinesia and tremor in patients with DLB. (The same results has been submitted at the Annual Meeting of the Japanese Society of Neurology [May 2018].)

References: [1] Murata M, Hasegawa K, Kanazawa I, et al. Randomized placebo-controlled trial of zonisamide in patients with Parkinson’s disease. Neurol Clin Neurosci. 2016; 4: 10-15. [2] Murata M, Odawara T, Hasegawa K, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized, double-blind phase 2 study. Neurology. 2018; 90: e664-e672.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-zonisamide-on-motor-symptoms-in-dementia-with-lewy-bodies-a-post-hoc-analysis-of-a-phase-3-study/