{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:55:56Z","timestamp":1791158156848,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,3]],"date-time":"2013-10-03T00:00:00Z","timestamp":1380758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"UCB Pharma"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,1]]},"abstract":"Summary<\/jats:title>Purpose<\/jats:title>To evaluate the safety and tolerability of adjunctive brivaracetam (BRV<\/jats:styled-content>), a high\u2010affinity synaptic vesicle protein 2A<\/jats:styled-content> (SV<\/jats:styled-content>2A<\/jats:styled-content>) ligand, in adults with uncontrolled epilepsy. Efficacy was also assessed in patients with focal seizures as a secondary objective, and explored by descriptive analysis in patients with generalized seizures.<\/jats:p><\/jats:sec>Methods<\/jats:title>This was a phase III<\/jats:styled-content>, randomized, double\u2010blind, placebo (PBO<\/jats:styled-content>)\u2010controlled flexible dose trial (N<\/jats:styled-content>01254\/NCT<\/jats:styled-content>00504881) in adults (16\u201370\u00a0years) with uncontrolled epilepsy (up to 20% could be patients with generalized epilepsy). After a prospective 4\u2010week baseline, patients were randomized (3:1) to b.i.d. BRV<\/jats:styled-content> or PBO<\/jats:styled-content>, initiated at 20\u00a0mg\/day and increased, as needed, to 150\u00a0mg\/day during an 8\u2010week dose\u2010finding period. This was followed by an 8\u2010week stable\u2010dose maintenance period. The treatment period comprised the dose\u2010finding period plus the maintenance period (16\u00a0weeks).<\/jats:p><\/jats:sec>Key Findings<\/jats:title>A total of 480 patients were randomized (BRV<\/jats:styled-content> 359, PBO<\/jats:styled-content> 121); of these, 431 had focal epilepsy and 49 had generalized epilepsy. Ninety percent BRV<\/jats:styled-content>\u2010 and 91.7% PBO<\/jats:styled-content>\u2010treated patients completed the study. Similar proportions of patients (BRV<\/jats:styled-content> 66.0%, PBO<\/jats:styled-content> 65.3%) reported adverse events (AE<\/jats:styled-content>s) during the treatment period. AE<\/jats:styled-content>s led to treatment discontinuation in 6.1% and 5.0% of BRV<\/jats:styled-content>\u2010 and PBO<\/jats:styled-content>\u2010treated patients, respectively. The incidence of AE<\/jats:styled-content>s declined from the dose\u2010finding (BRV<\/jats:styled-content> 56.0%, PBO<\/jats:styled-content> 55.4%) to the maintenance (BRV<\/jats:styled-content> 36.8%, PBO<\/jats:styled-content> 40.9%) period. The most frequent AE<\/jats:styled-content>s during the treatment period were headache (BRV<\/jats:styled-content> 14.2% vs. PBO<\/jats:styled-content> 19.8%), somnolence (BRV<\/jats:styled-content> 11.1% vs. PBO<\/jats:styled-content> 4.1%), and dizziness (BRV<\/jats:styled-content> 8.6% vs. PBO<\/jats:styled-content> 5.8%). The incidence of psychiatric AE<\/jats:styled-content>s was similar for BRV<\/jats:styled-content> and PBO<\/jats:styled-content> (BRV<\/jats:styled-content> 12.3%, PBO<\/jats:styled-content> 11.6%). In patients with focal seizures, the baseline\u2010adjusted percent reduction in seizure frequency\/week in the BRV<\/jats:styled-content> group (n\u00a0=\u00a0323) over PBO<\/jats:styled-content> (n\u00a0=\u00a0108) was 7.3% (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.125) during the treatment period. The median percent reduction in baseline\u2010adjusted seizure frequency\/week was 26.9% BRV<\/jats:styled-content> versus 18.9% PBO<\/jats:styled-content> (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.070), and the \u226550% responder rate was 30.3% BRV<\/jats:styled-content> versus 16.7% PBO<\/jats:styled-content> (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.006). In patients with generalized seizures only, the number of seizure days\/week decreased from 1.42 at baseline to 0.63 during the treatment period in BRV<\/jats:styled-content>\u2010treated patients (n\u00a0=\u00a036), and from 1.47 at baseline to 1.26 during the treatment period in PBO<\/jats:styled-content>\u2010treated patients (n\u00a0=\u00a013). The median percent reduction from baseline in generalized seizure days\/week was 42.6% versus 20.7%, and the \u226550% responder rate was 44.4% versus 15.4% in BRV<\/jats:styled-content>\u2010treated and PBO<\/jats:styled-content>\u2010treated patients, respectively.<\/jats:p><\/jats:sec>Significance<\/jats:title>Adjunctive BRV<\/jats:styled-content> given at individualized tailored doses (20\u2013150\u00a0mg\/day) was well tolerated in adults with uncontrolled epilepsy, and our results provided support for further evaluation of efficacy in reducing focal and generalized seizures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12391","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:57:34Z","timestamp":1381543054000},"page":"38-46","source":"Crossref","is-referenced-by-count":148,"title":["Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III<\/scp>, double\u2010blind, randomized, placebo\u2010controlled, flexible\u2010dose trial"],"prefix":"10.1111","volume":"55","author":[{"given":"Patrick","family":"Kwan","sequence":"first","affiliation":[{"name":"Division of Neurology Department of Medicine and Therapeutics Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong China"},{"name":"Departments of Medicine and Neurology The University of Melbourne Royal Melbourne Hospital Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Trinka","sequence":"additional","affiliation":[{"name":"Department of Neurology Christian\u2010Doppler\u2010Klinik Paracelsus Medical University Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Van Paesschen","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rektor","sequence":"additional","affiliation":[{"name":"First Department of Neurology St. Anne's University Hospital School of Medicine and Central European Centre for Technology (CEITEC) Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"UCB Pharma Biostatistics US Group Raleigh North Carolina U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lu","sequence":"additional","affiliation":[{"name":"UCB Pharma CNS Raleigh North Carolina 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