Randomized placebo-controlled trial of zonisamide in patients with Parkinson's disease

Background: We previously showed that zonisamide significantly improved parkinsonian symptoms by a multicenter, double-blind clinical trial. Aim: To confirm the efficacy of zonisamide on Parkinson's disease, a phase 3, randomized, placebo-controlled, multicenter, double-blind trial was carried out in Japan. Methods: Participants had advanced Parkinson's disease taking L-dopa with at least one other antiparkinson drug, but were developing a deterioration of response to L-dopa therapy. The trial consisted of a 2-week initial phase (singleblind, with administration of placebo) and a 12-week treatment phase (double-blind, with patients randomly assigned to either placebo, or zonisamide 25 or 50 mg/day). Patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS). Results: A total of 185 patients (mean age 64.8 years; mean duration 7.5 years) were included in the efficacy analysis (placebo, zonisamide 25 mg, 50 mg; 63, 61, 61 patients, respectively). When compared with the placebo group, the UPDRS Part III total score at final assessment (the primary end-point for efficacy) significantly improved (P = 0.029) in the zonisamide 25 mg group. After 12 weeks of therapy, the UPDRS Part III total score significantly improved in both the zonisamide 25 mg (P = 0.038) and 50 mg groups (P = 0.049), compared with the placebo group. Neither the zonisamide 25 mg nor 50 mg group differed significantly from the placebo group in the incidence of adverse events (P = 0.363 and P = 0.713, respectively). Conclusion: These findings confirmed that zonisamide is well tolerated and efficacious in the treatment of advanced Parkinson's disease.