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Safety and efficacy of perampanel in advanced Parkinson's disease: A randomized, placebo-controlled study

Authors


  • Potential conflict of interest: This study and editorial support were sponsored by Eisai Co., Ltd. No compensation was provided to the authors for their work on this manuscript. All authors, except for Dr. Squillacote, received compensation from Eisai for their site's conduct of the study. Drs. Barone, Lees, and Oertel received honoraria from Eisai as members of the Advisory Board of this study. Dr. Rascol has received unrestricted scientific grant and honoraria from Eisai for his advice to the company on this project. Dr. Dodel received honoraria from Eisai for presenting the study at meetings. Drs. Katzenschlager, Poewe, Kostic, and Ruzicka received honoraria from Eisai for consulting in relation to this study. Dr. Emre has been on the Protocol Development and Advisory Committee for the study and received honoraria for his advice. Dr. Onofrj received honoraria from Eisai in his capacity as Principal Investigator.

Abstract

Perampanel, a novel, noncompetitive, selective AMPA-receptor antagonist demonstrated evidence of efficacy in reducing motor symptoms in animal models of Parkinson's disease (PD). We assessed the safety and efficacy of perampanel for treatment of “wearing off” motor fluctuations in patients with PD. Patients (N = 263) were randomly assigned to once-daily add-on 0.5, 1, or 2 mg of perampanel or placebo. The primary objective was to determine whether there was a dose-response relationship for efficacy among the 3 perampanel doses and placebo. The primary efficacy endpoint for each treatment was measured as the least-squares (LS) mean change from baseline to week 12 in percent “off” time reduction during the waking day, as recorded by patient diaries. The primary efficacy analysis was a 1-sided Williams test for dose-response trend at the 0.025 level of significance. At week 12, dose-response trends, as determined by the Williams test, were not statistically significant for LS mean reduction in percent “off” time during the waking day (P = 0.061, with significance defined as P ≤ 0.025). The 2 higher perampanel doses (ITT population; n = 258) produced nonsignificant reductions from baseline to week 12 in percent “off” time during the waking day versus placebo (7.59%, P= 0.421 [1 mg], 8.60%, P = 0.257 [2 mg] versus 5.05% [placebo]; significance for pairwise comparisons defined as P ≤ 0.05). There were no significant changes in dyskinesia or cognitive function in any perampanel group versus placebo. Adverse events were similar across treatment groups. Perampanel treatment was well tolerated and safe, but failed to achieve statistical significance in primary and secondary endpoints. © 2010 Movement Disorder Society

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