title: 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.affiliation: Department of Neuroscience, IRCCS San Raffaele, Rome, Italy. fabstocc@tin.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.forename: Rupam
authors.initials: R
authors.lastname: Borgohain
authors.forename: Marco
authors.initials: M
authors.lastname: Onofrj
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: Mohit
authors.initials: M
authors.lastname: Bhatt
authors.forename: Valentina
authors.initials: V
authors.lastname: Lucini
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Giuliani
authors.forename: Ravi
authors.initials: R
authors.lastname: Anand
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001596:Benzylamines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D001596:Benzylamines; D018491:Dopamine Agonists; C092797:safinamide; D000409:Alanine