{"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":1790889515964,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,8]],"date-time":"2013-11-08T00:00:00Z","timestamp":1383868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"UCB Pharma"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Brivaracetam (<jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content>) is a novel high\u2010affinity synaptic vesicle protein 2A ligand currently being investigated for the treatment of epilepsy. The purpose of this phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> study was to evaluate the efficacy and safety\/tolerability of adjunctive <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> in adults with uncontrolled partial\u2010onset (focal) seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a prospective, multicenter, randomized, double\u2010blind, placebo\u2010controlled, parallel\u2010group, fixed\u2010dose trial (N01253; NCT00464269). Adults aged 16\u201370\u00a0years with well\u2010characterized partial epilepsy not fully controlled despite treatment with one or two antiepileptic drugs (<jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s) were enrolled. Patients who experienced eight or more partial\u2010onset seizures, whether or not secondarily generalized, during the 8\u2010week prospective baseline period were randomized (1:1:1:1) to receive twice\u2010daily placebo (<jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>) or <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> (5, 20, or 50\u00a0mg\/day) without titration. The primary efficacy endpoint was percent reduction over <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> in baseline\u2010adjusted partial\u2010onset seizure frequency\/week during the 12\u2010week treatment period. Comparison of <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> with <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> was sequential (50, 20\u00a0mg\/day, then 5\u00a0mg\/day). Secondary endpoints included \u226550% responder rate and median percent reduction from baseline in partial\u2010onset seizure frequency\/week. Post hoc analyses included the primary efficacy endpoint evaluated over 28\u00a0days and exploratory subanalyses of efficacy by seizure subtype. Safety and tolerability assessments included treatment\u2010emergent adverse events (<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s), laboratory tests, electrocardiography, vital signs, and physical and neurologic examinations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>Of 400 patients randomized, 396 were included in the intent\u2010to\u2010treat (<jats:styled-content style=\"fixed-case\">ITT<\/jats:styled-content>) population (<jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> n\u00a0=\u00a098, <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 5\u00a0mg\/day n\u00a0=\u00a097, <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 20\u00a0mg\/day n\u00a0=\u00a0100, <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 50\u00a0mg\/day n\u00a0=\u00a0101) and 392 comprised the modified <jats:styled-content style=\"fixed-case\">ITT<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">mITT<\/jats:styled-content>) population. A total of 361 (91.2%) of 396 patients completed the study. Most patients (78.3%) were receiving two concomitant <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s. Percent reduction in partial\u2010onset seizure frequency\/week over <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> was \u22120.9% (p\u00a0=\u00a00.885) for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 5\u00a0mg\/day, 4.1% (p\u00a0=\u00a00.492) for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 20\u00a0mg\/day, and 12.8% (p\u00a0=\u00a00.025) for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 50\u00a0mg\/day (<jats:styled-content style=\"fixed-case\">mITT<\/jats:styled-content> population). Statistical significance was also achieved for the percent reduction over <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> in baseline\u2010adjusted partial\u2010onset seizure frequency\/28\u00a0days for <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 50\u00a0mg\/day (22.0%; p\u00a0=\u00a00.004) but not for the other <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> dose groups. In the <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 50\u00a0mg\/day group, statistical significance was also seen for the \u226550% responder rate (<jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 32.7% vs. <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> 16.7%; p\u00a0=\u00a00.008) and median percent reduction from baseline in partial\u2010onset seizure frequency\/week (<jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 30.5% vs. <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> 17.8%; p\u00a0=\u00a00.003). In the exploratory subanalysis by seizure subtype, median percent reduction from baseline in seizure frequency\/week and \u226550% responder rate were numerically greater than <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> 20 and 50\u00a0mg\/day groups for simple partial, complex partial, and secondarily generalized seizures. BRV was generally well tolerated, with the majority of TEAEs being mild\u2010to\u2010moderate in intensity. Of the TEAEs reported by \u22655% patients, those with a frequency &gt;3% higher than <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> for any dose of <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> compared with <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content> were somnolence, dizziness, fatigue, influenza, insomnia, nasopharyngitis, vomiting, diarrhea, urinary tract infection, and nausea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Adjunctive <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> at a daily dose of 50\u00a0mg was associated with statistically significant reductions in seizure frequency compared with <jats:styled-content style=\"fixed-case\">PBO<\/jats:styled-content>. All doses of <jats:styled-content style=\"fixed-case\">BRV<\/jats:styled-content> showed good tolerability throughout the study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12433","type":"journal-article","created":{"date-parts":[[2013,11,8]],"date-time":"2013-11-08T16:32:57Z","timestamp":1383928377000},"page":"57-66","source":"Crossref","is-referenced-by-count":235,"title":["Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: A phase <scp>III<\/scp> randomized, double\u2010blind, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"55","author":[{"given":"Victor","family":"Biton","sequence":"first","affiliation":[{"name":"Arkansas Epilepsy Program Little Rock Arkansas U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel F.","family":"Berkovic","sequence":"additional","affiliation":[{"name":"Epilepsy Research Centre and Department of Medicine The University of Melbourne, Austin Health Heidelberg Victoria 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