{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:27:58Z","timestamp":1789244878754,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T00:00:00Z","timestamp":1368144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Eisai Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Three phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> studies (304 [<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00699972], 305 [<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00699582], 306 [<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00700310]) evaluated perampanel, an \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid (<jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content>) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with partial seizures despite receiving 1\u20133 antiepileptic drugs were randomized to once\u2010daily placebo, perampanel 8 or 12\u00a0mg (studies 304, 305), or placebo, perampanel 2, 4, or 8\u00a0mg (study 306). Studies included a 6\u2010week baseline period and double\u2010blind treatment phase (6\u2010week titration; 13\u2010week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double\u2010blind phase) and percentage of patients achieving \u226550% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>The pooled intent\u2010to\u2010treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4\u00a0mg, \u221223.3%; 8\u00a0mg, \u221228.8%; 12\u00a0mg, \u221227.2%; placebo, \u221212.8%; p\u00a0&lt;\u00a00.01, each dose vs. placebo), as were 50% responder rates (perampanel 4\u00a0mg, 28.5%; 8\u00a0mg, 35.3%; 12\u00a0mg, 35.0%; placebo, 19.3%; p\u00a0&lt;\u00a00.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4\u00a0mg, \u221231.2%; 8\u00a0mg, \u221235.6%; 12\u00a0mg, \u221228.6%; placebo, \u221213.9%). Perampanel was generally well tolerated. The most frequent treatment\u2010emergent adverse events (<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s) were dizziness, somnolence, and headache. Most <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were mild\/moderate; relatively few patients experienced severe <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s (placebo, 5.4%; perampanel, 8.9%) or serious <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (<jats:styled-content style=\"fixed-case\">ECG<\/jats:styled-content>) findings, or vital signs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12212","type":"journal-article","created":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T15:18:45Z","timestamp":1368199125000},"page":"1481-1489","source":"Crossref","is-referenced-by-count":244,"title":["Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase <scp>III<\/scp> studies"],"prefix":"10.1111","volume":"54","author":[{"given":"Bernhard J.","family":"Steinhoff","sequence":"first","affiliation":[{"name":"Kork Epilepsy Center Kehl\u2010Kork Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elinor","family":"Ben\u2010Menachem","sequence":"additional","affiliation":[{"name":"Sahlgrenska Academy Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Ryvlin","sequence":"additional","affiliation":[{"name":"Citizen Hospital of Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Shorvon","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Kramer","sequence":"additional","affiliation":[{"name":"Eisai Neuroscience Product Creation Unit Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Satlin","sequence":"additional","affiliation":[{"name":"Eisai Neuroscience Product Creation Unit Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Squillacote","sequence":"additional","affiliation":[{"name":"Eisai Global Medical Affairs Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichen","family":"Yang","sequence":"additional","affiliation":[{"name":"Eisai Neuroscience Product Creation Unit Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Eisai Neuroscience Product Creation Unit Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Laurenza","sequence":"additional","affiliation":[{"name":"Eisai Neuroscience Product Creation Unit Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.10.027"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.02.035"},{"key":"e_1_2_7_4_1","unstructured":"Eisai Inc. 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