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

Abstract

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.

• Authors: Fabrizio Stocchi, Rupam Borgohain, Marco Onofrj, Anthony H V Schapira, Mohit Bhatt, Valentina Lucini, Rodolfo Giuliani, Ravi Anand, Study 015 Investigators
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 27 Issue 1 Pg. 106-12 (Jan 2012) ISSN: 1531-8257 [Electronic] United States
• PMID: 21913224 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Movement Disorder Society.

Chemical References

• Antiparkinson Agents
• Benzylamines
• Dopamine Agonists
• safinamide
• Alanine

Topics

• Adult
• Aged
• Aged, 80 and over
• Alanine (analogs & derivatives, pharmacokinetics, therapeutic use)
• Analysis of Variance
• Antiparkinson Agents (pharmacokinetics, therapeutic use)
• Benzylamines (pharmacokinetics, therapeutic use)
• Dopamine Agonists (pharmacology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• International Cooperation
• Male
• Middle Aged
• Parkinson Disease (drug therapy)
• Retrospective Studies
• Severity of Illness Index