{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:28:02Z","timestamp":1761514082101},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009655","name":"Sunovion","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether adjunctive eslicarbazepine acetate (<jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content>) could lead to exacerbation of seizures in some patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Post\u2010hoc analysis of data pooled from three Phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> trials of adjunctive <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> (studies 301, 302, and 304) for refractory partial\u2010onset seizures (<jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content>). Following an 8\u2010week baseline period, patients were randomized to receive placebo or <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> 400, 800, or 1,200\u00a0mg once daily (2\u2010week titration, 12\u2010week maintenance, 2\u20134\u00a0week tapering\u2010off periods). Patient seizure diary data and seizure treatment\u2010emergent adverse event (<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>) reports were pooled for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The modified intent\u2010to\u2010treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. <jats:italic>Titration period<\/jats:italic>: Compared with placebo (32\/21%), significantly smaller proportions of patients taking <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> 800\u00a0mg (20\/15%) and 1,200\u00a0mg (22\/12%) had a \u226525\/\u226550% increase in standardized seizure frequency (<jats:styled-content style=\"fixed-case\">SSF<\/jats:styled-content>) from baseline; there was no significant difference between placebo and <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> 400\u00a0mg. <jats:italic>Maintenance period<\/jats:italic>: Compared with placebo (20%), significantly smaller proportions of patients taking <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> (400\u00a0mg, 12%; 800\u00a0mg, 12%; 1,200\u00a0mg, 14%) had an increase in <jats:styled-content style=\"fixed-case\">SSF<\/jats:styled-content> \u226525%. When evaluating \u226550% increases in <jats:styled-content style=\"fixed-case\">SSF<\/jats:styled-content>, only <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> 800\u00a0mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic\u2010clonic (<jats:styled-content style=\"fixed-case\">sGTC<\/jats:styled-content>) seizures during baseline but had \u22651 <jats:styled-content style=\"fixed-case\">sGTC<\/jats:styled-content> seizure during maintenance treatment (placebo, 11%; <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> 400\u00a0mg, 5%; 800\u00a0mg, 10%; 1,200\u00a0mg, 5%). Fewer patients had a \u226525% increase in <jats:styled-content style=\"fixed-case\">sGTC<\/jats:styled-content> seizure frequency with <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> (400\u00a0mg, 11%; 800\u00a0mg, 9%; 1,200\u00a0mg, 14%) versus placebo (19%). The incidence of seizures reported as <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s was low in all treatment groups; incidences were generally lower with <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> versus placebo. <jats:italic>Tapering\u2010off period<\/jats:italic>: Similar proportions of patients taking <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> and placebo had a \u226525\/\u226550% increase in <jats:styled-content style=\"fixed-case\">SSF<\/jats:styled-content>. Seizure <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content> incidence was numerically higher with <jats:styled-content style=\"fixed-case\">ESL<\/jats:styled-content> versus placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Treatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12083","type":"journal-article","created":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T06:14:49Z","timestamp":1507097689000},"page":"459-466","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Incidence of seizure exacerbation and seizures reported as adverse events during adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three Phase <scp>III<\/scp> controlled trials"],"prefix":"10.1002","volume":"2","author":[{"given":"Mar","family":"Carre\u00f1o","sequence":"first","affiliation":[{"name":"Epilepsy Unit Hospital Clinic Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selim","family":"Benbadis","sequence":"additional","affiliation":[{"name":"Department of Neurology University of South Florida Tampa Florida U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Rocha","sequence":"additional","affiliation":[{"name":"BIAL \u2013 Portela &amp; C<sup>a<\/sup>., S.A. S. Mamede do Coronado (S. Rom\u00e3o e S. Mamede) Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Blum","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Inc. Marlborough Massachusetts U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Inc. 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