Funding agencies: Newron and Merck Serono
Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations
Article first published online: 9 DEC 2013
© 2013 The Authors. Movement Disorders published by Wiley on behalf of the International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 29, Issue 2, pages 229–237, February 2014
How to Cite
Borgohain, R., Szasz, J., Stanzione, P., Meshram, C., Bhatt, M., Chirilineau, D., Stocchi, F., Lucini, V., Giuliani, R., Forrest, E., Rice, P., Anand, R. and Study 016 Investigators (2014), Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Mov. Disord., 29: 229–237. doi: 10.1002/mds.25751
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
The Study 016 Investigators are listed in the Appendix.
- Issue published online: 20 FEB 2014
- Article first published online: 9 DEC 2013
- Manuscript Accepted: 18 OCT 2013
- Manuscript Revised: 10 OCT 2013
- Manuscript Received: 13 JUN 2013
- MAO-B inhibitor;
Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia. © 2013 International Parkinson and Movement Disorder Society