• Open Access

Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease

Authors


  • Relevant conflicts of interest/financial disclosures: Dr R. Borgohain has served on the scientific advisory board of Neuronova. Dr. J Szasz serves on the scientific advisory board of Abbott Pharmaceuticals, received funding for travel from the following pharmaceutical companies: Boehringer Ingelheim, Novartis, UCB pharmaceuticals and Lundbeck, and received honoraria for speaking engagements from the following pharmaceutical companies: Abbott, UCB, Novartis, TEVA, Boehringer Ingelheim, and GSK. Dr P. Stanzione serves on the scientific advisory board of UCB pharmaceuticals, received travel expenses and/or honoraria for lectures or educational activities not funded by industry, has received honoraria for speaking engagements from UCB, GlaxoSmithKline, Boehringer Ingelheim, and Chiesi, was the principal investigator for research sponsored by UCB pharmaceuticals in 2012 and received institutional support from Yale university for the IRIS trial, 2010-11-12. Dr. C. Meshram reports no conflicts of interest. Dr. M Bhatt has received honoraria for speaking engagements from the Movement Disorders Society. Dr. D. Chirilineau has received funding for travel to participate in scientific meetings from the following pharmaceutical companies: GlaxoSmithKline, Merck Sereno, Novartis, Ever Neuro Pharma, Lundbeck and Sanofi Aventis. Dr. F. Stocchi has served on scientific advisory boards for TEVA, Novartis, GSK, Lundbeck, IMPAX, Merk Serono, MSD, UCB and Chiesi pharmaceutical and has received research support for research on the pathophysiology of motor fluctuations in PD sponsored by Novartis, GSK. Dr. V. Lucini is an employee of Newron Pharmaceuticals. Dr. R. Giuliani is an employee of Newron Pharmaceuticals. Dr. E. Forrest is an employee of Newron Pharmaceuticals. Ms. P. Rice is an employee of Premier Research. Dr. R. Anand served on the scientific advisory boards of Astra Zeneca 2012, Hoffman LaRoche (AB member) 2011, 2012 and served on the scientific board of Sonexa 2011, is a reviewer and a member of the editorial board of the journal ‘European Neuropsychopharmacology' and reviewer for the journal ‘Experimental Neurology' and is a corporate consultant to: Abbot, Newron, Shire, Roche, Erydel, Takeda, Bioline, and Teva Pharmaceuticals.

  • Full financial disclosures and author roles may be found in the online version of this article.

  • Funding agencies: This study was supported by Newron and Merck Serono S.A., Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.

Abstract

In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P = 0.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression. © 2014 International Parkinson and Movement Disorder Society

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