A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson's disease patients†‡§
Funding agencies: The sponsor, Newron Pharmaceuticals S.p.A., was responsible for the study design, investigator selection, general oversight of the trial, and identification of the contract research organization responsible for day-to-day study management, monitoring, data management, and statistical analysis. Professor Pablo Martinez-Martin provided training for the UPDRS. The interpretation of the data and preparation of the manuscript were performed by the authors with the assistance of an independent medical writing agency, funded by Merck Serono. The decision to submit to Movement Disorders was made by the authors.
Relevant conflicts of interest/financial disclosures: F.S. and all the other participants of the clinical study received payment according to the number of patients included in the trial. F.S. has received honoraria for educational symposia and consultancy for Newron and Merck Serono. A.H.V.S. has received honoraria from Merck Serono for medical education symposia and for providing advice in the development of safinamide. R.A. has received honoraria for acting as a consultant for Newron Pharmaceuticals in the development of safinamide, in the conception and organization of this clinical trial, in the statistical design and critical review of the analysis, and in the conception, review, and critique of the manuscript for this article. M.O. has received honoraria for acting as a consultant for Newron Pharmaceuticals and from Merck Serono for an educational symposium. V.L. and R.G. are employees of Newron. R.B. and M.B. have nothing else to disclose.
Full financial disclosures and author roles may be found in the online version of this article.
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. © 2011 Movement Disorder Society
