title: Safety and efficacy of perampanel in advanced Parkinson's disease: a randomized, placebo-controlled study.
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 <or= 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 <or= 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.
authors.affiliation: German Competence Network on Parkinson's Disease, Department of Neurology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Karla
authors.initials: K
authors.lastname: Eggert
authors.forename: David
authors.initials: D
authors.lastname: Squillacote
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.forename: Regina
authors.initials: R
authors.lastname: Katzenschlager
authors.forename: Murat
authors.initials: M
authors.lastname: Emre
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Marco
authors.initials: M
authors.lastname: Onofrj
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kostic
authors.forename: Jagoda
authors.initials: J
authors.lastname: Potic
authors.forename: Evzen
authors.initials: E
authors.lastname: Ruzicka
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D011728:Pyridones / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D009570:Nitriles; D011728:Pyridones; D018091:Receptors, AMPA; C551441:perampanel