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Patients were titrated to 12\u00a0mg\/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open\u2010label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [<jats:styled-content style=\"fixed-case\">ECG]<\/jats:styled-content>, laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 1,216 patients, median exposure was 1.5\u00a0years (range 1\u00a0week to 3.3\u00a0years), with &gt;300 patients treated for &gt;2\u00a0years. Treatment retention was 58.5% at cutoff. AEs reported in \u226510% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in &gt;1% of patients (3.9% and 1.3%, respectively). The only serious <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s reported in &gt;1% of patients were epilepsy\u2010related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, <jats:styled-content style=\"fixed-case\">ECG<\/jats:styled-content> or laboratory parameters were seen. After titration\/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9\u00a0months (in 980 patients with \u22659\u00a0months' exposure) and 58% and 60%, respectively, at 2\u00a0years (in the 337 patients with 2\u00a0years' exposure). Median percentage reduction in frequency of secondarily generalized (<jats:styled-content style=\"fixed-case\">SG<\/jats:styled-content>) seizures ranged from 77% at 9\u00a0months (N\u00a0=\u00a0422) to 90% at 2\u00a0years (N\u00a0=\u00a0141). Among the 694 patients with maintenance data \u22651\u00a0year, 5.3% were seizure\u2010free for the entire year.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>No new safety signals emerged during up to 3\u00a0years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in <jats:styled-content style=\"fixed-case\">SG<\/jats:styled-content> seizures.<\/jats:p><jats:p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/epi.12643\/supinfo\">here<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12643","type":"journal-article","created":{"date-parts":[[2014,5,27]],"date-time":"2014-05-27T14:58:14Z","timestamp":1401202694000},"page":"1058-1068","source":"Crossref","is-referenced-by-count":105,"title":["Long\u2010term safety of perampanel and seizure outcomes in refractory partial\u2010onset seizures and secondarily generalized seizures: Results from phase <scp>III<\/scp> extension study 307"],"prefix":"10.1111","volume":"55","author":[{"given":"Gregory L.","family":"Krauss","sequence":"first","affiliation":[{"name":"Johns Hopkins University Baltimore Maryland U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[{"name":"National Neurological Institute IRCSS C Mondino Foundation Pavia Italy"},{"name":"Department of Internal Medicine and Therapeutics University of Pavia Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elinor","family":"Ben\u2010Menachem","sequence":"additional","affiliation":[{"name":"Sahlgrenska Academy Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Kwan","sequence":"additional","affiliation":[{"name":"The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China"},{"name":"Royal Melbourne Hospital University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry J.","family":"Shih","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville Florida U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Cl\u00e9ment","sequence":"additional","affiliation":[{"name":"Charles LeMoyne Hospital Greenfield Park Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makarand","family":"Bagul","sequence":"additional","affiliation":[{"name":"Eisai Ltd. 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