Levodopa is effective for the motor symptoms of
Parkinson's disease (PD), but is associated with motor fluctuations and
dyskinesia. Many patients require add-on
therapy to improve motor fluctuations without exacerbating
dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of
safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to
l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral
safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome
dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome
dyskinesia were 1.36 ± 2.625 hours for
safinamide 100 mg/day, 1.37 ± 2.745 hours for
safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both
safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both
safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of
safinamide 50 mg/day or 100 mg/day to
l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome
dyskinesia, decreased off time, and improved
parkinsonism, indicating that
safinamide improves motor symptoms and
parkinsonism without worsening
dyskinesia.