{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:48:04Z","timestamp":1789044484850,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Aquestive Therapeutics, Inc"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Clobazam oral soluble film (<jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content>) is a novel dosage form under development for the adjunctive treatment of seizures associated with Lennox\u2010Gastaut syndrome. The present study was undertaken to assess the pharmacokinetics of clobazam administered as single doses of <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content> 20 and 10 mg compared with clobazam tablets (<jats:styled-content style=\"fixed-case\">CTAB<\/jats:styled-content>) 20 and 10 mg in healthy adults. A secondary objective was to assess the safety and tolerability of single doses of <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content> 20 and 10 mg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 51 adult volunteers were enrolled in a single\u2010dose, open\u2010label, randomized four\u2010sequence, four\u2010period, crossover study with treatments (A) <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content> 20 mg, (B) <jats:styled-content style=\"fixed-case\">CTAB<\/jats:styled-content> 20 mg, (C) <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content> 10 mg, and (D) <jats:styled-content style=\"fixed-case\">CTAB<\/jats:styled-content> 10 mg. Pharmacokinetic sampling for clobazam and N\u2010desmethylclobazam was carried out until 21 days postdose with a 28\u2010day washout. Subjects were monitored for adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s) throughout the study. Visual inspections of the administration site were performed before and after <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content> administration to monitor for mucosal irritation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>COSF at single doses of 10 and 20 mg was bioequivalent to <jats:styled-content style=\"fixed-case\">CTAB<\/jats:styled-content> at equivalent doses for both clobazam and its active metabolite N\u2010desmethylclobazam. The pharmacokinetics of both formulations was dose\u2010proportional at doses of 10 and 20 mg. The number of <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s and the number of subjects experiencing <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s were dose\u2010related across the treatment groups, with somnolence the most common event. None of these events was severe or serious, and most were mild. There was no evidence for local irritation at the administration site following <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>COSF is a novel clobazam dosage form that is bioequivalent to <jats:styled-content style=\"fixed-case\">CTAB<\/jats:styled-content>. Because of its ease of administration, <jats:styled-content style=\"fixed-case\">COSF<\/jats:styled-content> may be expected to improve adherence, reduce likelihood of dosing error, and provide more accurate dosing than formulations of clobazam that are currently available.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14581","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T02:34:53Z","timestamp":1540434893000},"page":"2153-2161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacokinetics of clobazam oral soluble film"],"prefix":"10.1111","volume":"59","author":[{"given":"Allen H.","family":"Heller","sequence":"first","affiliation":[{"name":"Pharma Study Design LLC Woodbridge Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Wargacki","sequence":"additional","affiliation":[{"name":"Aquestive Therapeutics, Inc Warren New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie","family":"Jung","sequence":"additional","affiliation":[{"name":"Aquestive Therapeutics, Inc Warren New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla V.","family":"Buan","sequence":"additional","affiliation":[{"name":"Aquestive Therapeutics, Inc Warren New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Syneos Health Clinical Solutions Early Phase Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Mark","family":"Schobel","sequence":"additional","affiliation":[{"name":"Aquestive Therapeutics, Inc Warren New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285614521314"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/75761"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2006.11.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/11599020-000000000-00000"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812463609"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088456"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318232de76"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2012.09.039"},{"key":"e_1_2_8_10_1","unstructured":"Indivior.FDA approved label. Suboxone\u00ae (buprenorphine and naloxone) sublingual film for sublingual or buccal use.2017.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/022410s023lbl.pdf. Accessed September 4 2018."},{"key":"e_1_2_8_11_1","unstructured":"Galena Biopharma.FDA approved label. Zuplenz (ondansetron) oral soluble film.2014.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/022524s003lbl.pdf. Accessed September 4 2018."},{"issue":"1","key":"e_1_2_8_12_1","first-page":"S15","article-title":"Evolution and management of Lennox\u2010Gastaut syndrome through adolescence and into adulthood: are seizures always the primary issue?","volume":"13","author":"Kerr M","year":"2011","journal-title":"Epileptic Disord"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/seiz.2000.0483"},{"key":"e_1_2_8_14_1","first-page":"149","article-title":"Experimental designs balanced for the estimation of residual effects of treatments","volume":"2","author":"Williams E","year":"1949","journal-title":"Aust J Sci Res"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000272"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31827ada88"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70292-8"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3225"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-0357"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.14581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.14581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.14581","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.14581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:07:41Z","timestamp":1692871661000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.14581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,24]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/epi.14581"],"URL":"https:\/\/doi.org\/10.1111\/epi.14581","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,24]]},"assertion":[{"value":"2018-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}