{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:03:54Z","timestamp":1790996634199,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T00:00:00Z","timestamp":1269820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2010,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Perampanel, a novel, noncompetitive, selective AMPA\u2010receptor 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 \u201cwearing off\u201d motor fluctuations in patients with PD. Patients (N = 263) were randomly assigned to once\u2010daily add\u2010on 0.5, 1, or 2 mg of perampanel or placebo. The primary objective was to determine whether there was a dose\u2010response relationship for efficacy among the 3 perampanel doses and placebo. The primary efficacy endpoint for each treatment was measured as the least\u2010squares (LS) mean change from baseline to week 12 in percent \u201coff\u201d time reduction during the waking day, as recorded by patient diaries. The primary efficacy analysis was a 1\u2010sided Williams test for dose\u2010response trend at the 0.025 level of significance. At week 12, dose\u2010response trends, as determined by the Williams test, were not statistically significant for LS mean reduction in percent \u201coff\u201d time during the waking day (<jats:italic>P<\/jats:italic> = 0.061, with significance defined as <jats:italic>P<\/jats:italic> \u2264 0.025). The 2 higher perampanel doses (ITT population; n = 258) produced nonsignificant reductions from baseline to week 12 in percent \u201coff\u201d time during the waking day versus placebo (7.59%, <jats:italic>P<\/jats:italic>= 0.421 [1 mg], 8.60%, <jats:italic>P<\/jats:italic> = 0.257 [2 mg] versus 5.05% [placebo]; significance for pairwise comparisons defined as <jats:italic>P<\/jats:italic> \u2264 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. \u00a9 2010 Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.22974","type":"journal-article","created":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T15:55:26Z","timestamp":1269878126000},"page":"896-905","source":"Crossref","is-referenced-by-count":69,"title":["Safety and efficacy of perampanel in advanced Parkinson's disease: A randomized, placebo\u2010controlled 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in cooperation with the German Competence Network on Parkinson's Disease","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,5,5]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033447"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.1.11"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.035980"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S031716710003849X"},{"key":"e_1_2_7_6_2","first-page":"CD004554","article-title":"Catechol\u2010O\u2010methyltransferase inhibitors for levodopa\u2010induced complications in Parkinson's disease","volume":"4","author":"Deane KHO","year":"2004","journal-title":"Cochrane Database Syst 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