Long-Term Efficacy and Safety of Zonisamide for Treatment of Parkinsonism in Patients With Dementia With Lewy Bodies: An Open-Label Extension of a Phase three Randomized Controlled Trial.

ABSTRACT Objectives To evaluate the long-term efficacy and safety of zonisamide, an antiepileptic agent, in dementia with Lewy bodies (DLB). Design Phase three clinical trial with 12 week, randomized, placebo-controlled, double-blind, and subsequent 40 week, open-label, extension periods. Setting A total of 109 centers in Japan between April 2015 and November 2017. Participants Outpatients diagnosed with probable DLB. Intervention Outpatients were randomly assigned to receive placebo (P) or zonisamide 25 or 50 mg/day for 12 weeks. In the subsequent open-label 40 week period, all patients initially received zonisamide 25 mg/day for at least 2 weeks followed by optional flexible dosing with zonisamide 25 or 50 mg/day for the remaining period. Measurements The primary outcome was efficacy on motor symptoms, assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score, over the total 52 week trial period. Effects on behavioral and psychological symptoms of dementia and cognitive function, and safety were also evaluated. Results In total, 335 patients were included in the long-term analysis: 106, 117, and 112 in the P-, 25mg-, and 50mg-Flex groups, respectively. UPDRS-III score continued to improve for an additional 12 to 16 weeks in the open-label period (mean [standard deviation] change from baseline at Week 28: −5.1 [7.3] and −6.3 [8.2] in the 25mg- and 50mg-Flex groups) and remained almost constant thereafter. No unexpected neurological or psychiatric adverse events occurred, and no adverse events increased in incidence in the open-label period. Conclusions Long-term treatment with zonisamide was well tolerated and yielded sustained improvement in motor symptoms. Trial registration JapicCTI-152839 (Registered on 9 March 2015) https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152839