Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study.

Abstract Introduction Safinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to l -DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off. Methods This 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on l -DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index. Results A total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p  Conclusion As an adjunct to l -DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.