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Safety and efficacy of perampanel in advanced Parkinson's disease: A randomized, placebo‐controlled study
Author(s) -
Eggert Karla,
Squillacote David,
Barone Paolo,
Dodel Richard,
Katzenschlager Regina,
Emre Murat,
Lees Andrew J.,
Rascol Olivier,
Poewe Werner,
Tolosa Eduardo,
Trenkwalder Claudia,
Onofrj Marco,
Stocchi Fabrizio,
Nappi Giuseppe,
Kostic Vladimir,
Potic Jagoda,
Ruzicka Evzen,
Oertel Wolfgang
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.22974
Subject(s) - perampanel , placebo , dyskinesia , adverse effect , medicine , population , antagonist , anesthesia , clinical endpoint , psychology , randomized controlled trial , parkinson's disease , disease , alternative medicine , receptor , environmental health , pathology
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