A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson's disease patients

• Published in: Movement disorders 2012-01, Vol.27 (1), p.106-112
• Main Authors: Stocchi, Fabrizio, Borgohain, Rupam, Onofrj, Marco, Schapira, Anthony H.V., Bhatt, Mohit, Lucini, Valentina, Giuliani, Rodolfo, Anand, Ravi
• Format: Article
• Language: English
• Subjects: add-on; Adult; Aged; Aged, 80 and over; Alanine - analogs & derivatives; Alanine - pharmacokinetics; Alanine - therapeutic use; Analysis of Variance; Antiparkinson Agents - pharmacokinetics; Antiparkinson Agents - therapeutic use; Benzylamines - pharmacokinetics; Benzylamines - therapeutic use; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dopamine; Dopamine Agonists - pharmacology; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; International Cooperation; Male; Medical sciences; Middle Aged; motor function; Neurology; Parkinson Disease - drug therapy; Parkinson's disease; Retrospective Studies; safinamide; Severity of Illness Index; α-aminoamide
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.23954

Safinamide is an α‐aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add‐on to dopamine agonist (DA) therapy in early‐stage PD. In this 24‐week, double‐blind study, patients with early PD receiving a stable dose of a single DA were randomized to once‐daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty‐nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were −3.90 for safinamide 200 mg, −6.0 for safinamide 100 mg and −3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: −0.4; 95% confidence interval (CI): −2.3–1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: −1.9; 95% CI: −3.7 to −0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation. © 2011 Movement Disorder Society