{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T04:36:33Z","timestamp":1771043793971,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100015661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Despite introduction of several antiseizure medications over the past two decades, treatment options for childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) remain limited. We report the innovative adaptive design of an ongoing phase 2\/3 trial to evaluate efficacy, safety, and tolerability of brivaracetam (BRV) monotherapy in patients 2\u201325\u2009years of age with CAE or JAE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>N01269 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>: NCT04666610; start: July 2021; expected completion: 2024) is a randomized, dose\u2010finding and confirmatory, double\u2010blind, placebo\u2010controlled, parallel\u2010group, multicenter trial. The trial consists of a dose\u2010selection and assessment for futility stage, followed by an optimal\u2010dose stage after interim analysis. Both stages include an up to 2\u2010week screening period, a 2\u2010week placebo\u2010controlled period, and an 11\u2010week active treatment period (10\u2009weeks of initial treatment followed by a 24\u2010hour electroencephalogram [EEG] and an additional week of active treatment for 24\u2010hour EEG assessment). Patients who are absence seizure\u2010free will enter an up to 4\u2010week randomized withdrawal period. Efficacy assessments will be based on 24\u2010hour EEG and seizure diaries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This two\u2010stage adaptive trial design allows investigation of two potentially efficacious BRV doses, where one dose is dropped in favor of the other dose with a better benefit\u2013risk profile. This allows for a combined phase 2 dose\u2010finding and phase 3 confirmatory efficacy trial, which reduces the number of patients needed to be recruited and reduces trial duration. A randomized withdrawal period is included to evaluate sustainability of treatment effect over time and to allow for placebo control while minimizing placebo exposure. Use of EEG capture in addition to seizure diaries offers a robust mechanism of detecting seizure activity and measuring treatment effect. Positive efficacy and safety\/tolerability data may support the use of BRV as monotherapy for CAE or JAE, providing another treatment option and representing long\u2010delayed progress in the treatment of absence seizures in these populations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12628","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T06:56:51Z","timestamp":1658127411000},"page":"588-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and tolerability of brivaracetam monotherapy in childhood and juvenile absence epilepsy: An innovative adaptive trial design"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8995-9792","authenticated-orcid":false,"given":"Thomas","family":"Bast","sequence":"first","affiliation":[{"name":"Epilepsy Center Kork Kehl Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Liv","family":"Schulz","sequence":"additional","affiliation":[{"name":"UCB Pharma Monheim am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florin","family":"Floricel","sequence":"additional","affiliation":[{"name":"UCB Pharma Monheim am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Morita","sequence":"additional","affiliation":[{"name":"UCB Pharma Morrisville North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jody\u00a0M.","family":"Cleveland","sequence":"additional","affiliation":[{"name":"UCB Pharma Morrisville North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6366-1525","authenticated-orcid":false,"given":"Jan\u2010Peer","family":"Elshoff","sequence":"additional","affiliation":[{"name":"UCB Pharma Monheim am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1989.tb05316.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.10.014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389601100611"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00805.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0902014"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2008.03099.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02976.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1684\/epd.2007.0144","article-title":"Treatment of pediatric epilepsy: European expert opinion, 2007","volume":"9","author":"Wheless JW","year":"2007","journal-title":"Epileptic Disord"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380502000101"},{"key":"e_1_2_10_11_1","unstructured":"Parke\u2010Davis.Zarontin\u00ae (ethosuximide) prescribing information 2021. 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