{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:18:35Z","timestamp":1790889515971,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T00:00:00Z","timestamp":1444953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Brivaracetam (<jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content>), a selective and high\u2010affinity synaptic vesicle protein 2A ligand, is in development as adjunctive treatment for partial\u2010onset (focal) seizures (<jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content>). This phase 3 study (N01358; <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>01261325) aimed to confirm the efficacy and safety\/tolerability of <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> in adults (\u226516\u201380 years) with <jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, double\u2010blind, placebo\u2010controlled, multicenter study enrolled patients with uncontrolled <jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content> despite ongoing treatment with 1\u20132 antiepileptic drugs. Patients exposed to levetiracetam \u226490 days before visit 1 were excluded. Patients entered an 8\u2010week prospective baseline period, followed by a 12\u2010week treatment period when they were randomized 1:1:1 to placebo (<jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 100 mg\/day, or BRV 200 mg\/day, started without up\u2010titration. The co\u2010primary efficacy outcomes were percent reduction over placebo in 28\u2010day adjusted <jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content> frequency, and \u226550% responder rate based on percent reduction in <jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content> frequency from baseline to the treatment period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven hundred sixty\u2010eight patients were randomized; 760 were included in the efficacy analysis: 259, 252, and 249 in <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> BRV<\/jats:styled-content> 100 mg\/day, and BRV 200 mg\/day groups, respectively. Percent reduction over <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> in 28\u2010day adjusted seizure frequency (95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>]) was 22.8% for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 100 mg\/day (13.3\u201331.2%; p &lt; 0.001) and 23.2% for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 200 mg\/day (13.8\u201331.6%; p &lt; 0.001). The \u226550% responder rate (odds ratio vs. <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) was 21.6% for <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>, 38.9% for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 100 mg\/day (2.39; 1.6\u20133.6; p &lt; 0.001), and 37.8% for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 200 mg\/day (2.19; 1.5\u20133.3; p &lt; 0.001). Treatment\u2010emergent adverse events (<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s) occurred in 155 (59.4%) of 261 <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> patients versus 340 (67.6%) of 503 <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content>\u2010treated patients (safety population). Discontinuation rates due to <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were 3.8%, 8.3%, and 6.8% for <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> BRV<\/jats:styled-content> 100 mg\/day, and BRV 200 mg\/day, respectively. Most frequent <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> versus <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content>) were somnolence (7.7% vs. 18.1%), dizziness (5.0% vs. 12.3%), and fatigue (3.8% vs. 9.5%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Adjunctive <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 100 and 200 mg\/day was efficacious in reducing <jats:styled-content style=\"fixed-case\">POS<\/jats:styled-content> in adults without concomitant levetiracetam use and was well tolerated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13212","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T12:23:27Z","timestamp":1444998207000},"page":"1890-1898","source":"Crossref","is-referenced-by-count":222,"title":["A randomized, double\u2010blind, placebo\u2010controlled, multicenter, parallel\u2010group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial\u2010onset seizures"],"prefix":"10.1111","volume":"56","author":[{"given":"Pavel","family":"Klein","sequence":"first","affiliation":[{"name":"Mid\u2010Atlantic Epilepsy and Sleep Center Bethesda Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Schiemann","sequence":"additional","affiliation":[{"name":"UCB Pharma Raleigh North Carolina U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Whitesides","sequence":"additional","affiliation":[{"name":"UCB Pharma Raleigh North Carolina 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