{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:15:56Z","timestamp":1788243356013,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was undertaken to examine long\u2010term (up to 7.8\u00a0years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open\u2010label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients who completed the 12\u2010week, multicenter, multinational, double\u2010blind, randomized, placebo\u2010controlled C013\u00a0study, which examined adjunctive cenobamate treatment of adults with uncontrolled focal seizures, were eligible to enroll in the OLE. During the OLE, dose adjustments of cenobamate and concomitant ASMs were allowed. Safety assessments included frequency of treatment\u2010emergent adverse events (TEAEs) and serious TEAEs, TEAE severity, and TEAEs leading to discontinuation. Probability of patient continuation in the OLE was examined using a Kaplan\u2013Meier analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred forty\u2010nine patients entered the OLE (median duration of cenobamate treatment = 6.25\u00a0years). As of the data cutoff, 57% of patients (85\/149) remained in the OLE (median treatment duration = 6.8\u00a0years, range = 6.4\u20137.8\u00a0years). The median modal daily cenobamate dose was 200\u00a0mg (range = 50\u2013400\u00a0mg). The probability of treatment continuation at 1\u20136\u00a0years of cenobamate treatment was 73%, 67%, 63%, 61%, 60%, and 59%, respectively. Among patients who continued at 1\u00a0year (<jats:italic>n<\/jats:italic>\u00a0=\u00a0107), the probability of continuing at Years 2\u20135 was 92%, 87%, 83%, and 82%. The most common discontinuation reasons were patient withdrawal (19.5%, 29\/149), adverse event (10.1%, 15\/149), and lack of efficacy (5.4%, 8\/149). TEAEs leading to discontinuation in 1% or more of patients were fatigue (1.3%, 2\/149), ataxia (1.3%, 2\/149), and memory impairment or amnesia (1.3%, 2\/149). Dizziness (32.9%, 49\/149), headache (26.8%, 40\/149), and somnolence (21.5%, 32\/149) were the most frequently reported TEAEs and were primarily mild or moderate in severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Long\u2010term retention in the C013 OLE study demonstrated sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8\u00a0years in adults with treatment\u2010resistant focal seizures taking one to three ASMs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17007","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T11:02:28Z","timestamp":1626174148000},"page":"2142-2150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Long\u2010term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: Open\u2010label extension of a randomized clinical study"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline A.","family":"French","sequence":"first","affiliation":[{"name":"New York University Langone Comprehensive Epilepsy Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve S.","family":"Chung","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Banner\u2010University Medical Center University of Arizona Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-6039","authenticated-orcid":false,"given":"Gregory L.","family":"Krauss","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Kun","family":"Lee","sequence":"additional","affiliation":[{"name":"Adult Comprehensive Epilepsy Center Seoul National University Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Maciejowski","sequence":"additional","affiliation":[{"name":"NZOZ Diagnomed Clinical Research Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-3980","authenticated-orcid":false,"given":"William E.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Care Center for Children and Adults St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-6006","authenticated-orcid":false,"given":"Michael R.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Kamin","sequence":"additional","affiliation":[{"name":"SK Life Science 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