Zonisamide improves wearing off in Parkinson's disease without exacerbating dyskinesia: Post hoc analysis of phase 2 and phase 3 clinical trials

Introduction: Although phase 2 and 3 clinical trials in Japan showed that zonisamide improved wearing off in patients with Parkinson's disease (PD), no studies to date have evaluated whether zonisamide improves wearing off in patients with PD without exacerbating dyskinesia. Therefore, we examined this hypothesis in a post hoc analysis of pooled data from the previous phase 2 and 3 trials. Methods: Both trials evaluated zonisamide 25 mg and 50 mg versus placebo during a 12-week treatment period. In our analysis, primary efficacy variables were adjusted mean change in wearing off (evaluated as change in "off" time) and dyskinesia from baseline to 12 weeks. Dyskinesia was evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) part 4 items 32 (4-32; duration of dyskinesia) and 33 (4-33; disability of dyskinesia) score. Criteria outcomes included rates of patients meeting specific criteria based on off time plus UPDRS part 432 or 4-33. Results: A total of 212 patients were included in this analysis. Zonisamide 50 mg significantly reduced off time and UPDRS part 4-33 score at week 12 versus placebo without increasing UPDRS part 4-32 score. The proportion of patients receiving zonisamide 50 mg who met the criterion "Off time decreased and UPDRS part 4-33 score did not increase" was significantly higher than that of patients receiving placebo. Conclusion: Zonisamide improves wearing off without exacerbating dyskinesia in Japanese patients with PD. Moreover, zonisamide 50 mg may improve dyskinesia. Further studies are needed to prospectively determine the benefits and clinical relevance of zonisamide on dyskinesia.