{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:19:14Z","timestamp":1789100354189,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012739","name":"Zogenix","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100012739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, randomized, double\u2010blind, placebo\u2010controlled, parallel\u2010group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2\u201318\u2009years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had \u22656 convulsive seizures during the 6\u2010week baseline period were randomized to placebo, fenfluramine .2\u2009mg\/kg\/day, or fenfluramine .7\u2009mg\/kg\/day (1:1:1 ratio) administered orally (maximum dose\u2009=\u200926\u2009mg\/day). Doses were titrated over 2\u2009weeks and maintained for an additional 12\u2009weeks. The primary endpoint was a comparison of the monthly convulsive seizure frequency (MCSF) during baseline and during the combined titration\u2013maintenance period in patients given fenfluramine .7\u2009mg\/kg\/day versus patients given placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 169 patients were screened, and 143 were randomized to treatment. Mean age was 9.3\u2009\u00b1\u20094.7\u2009years (\u00b1SD), 51% were male, and median baseline MCSF in the three groups ranged 12.7\u201318.0 per 28\u2009days. Patients treated with fenfluramine .7\u2009mg\/kg\/day demonstrated a 64.8% (95% confidence interval\u2009=\u200951.8%\u201374.2%) greater reduction in MCSF compared with placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001). Following fenfluramine .7\u2009mg\/kg\/day, 72.9% of patients had a\u2009\u226550% reduction in MCSF compared with 6.3% in the placebo group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001). The median longest seizure\u2010free interval was 30\u2009days in the fenfluramine .7\u2009mg\/kg\/day group compared with 10\u2009days in the placebo group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001). The most common adverse events (&gt;15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17737","type":"journal-article","created":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T07:19:04Z","timestamp":1691306344000},"page":"2653-2666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo\u2010controlled clinical trial"],"prefix":"10.1111","volume":"64","author":[{"given":"Joseph","family":"Sullivan","sequence":"first","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7118-0139","authenticated-orcid":false,"given":"Lieven","family":"Lagae","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-4829","authenticated-orcid":false,"given":"J. Helen","family":"Cross","sequence":"additional","affiliation":[{"name":"University College London, National Institute for Health and Care Research Biomedical Research Centre, Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"New York University Langone Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-7079","authenticated-orcid":false,"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Meyer Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-0827","authenticated-orcid":false,"given":"Kelly G.","family":"Knupp","sequence":"additional","affiliation":[{"name":"University of Colorado, Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Laux","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Nikanorova","sequence":"additional","affiliation":[{"name":"Danish Epilepsy Center  Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-7312","authenticated-orcid":false,"given":"Tilman","family":"Polster","sequence":"additional","affiliation":[{"name":"Department of Epileptology (Krankenhaus Mara, Bethel Epilepsy Center) Bielefeld University Medical School  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Talwar","sequence":"additional","affiliation":[{"name":"University of Arizona Health Sciences Center  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berten","family":"Ceulemans","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology University of Antwerp  Edegem Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-4074","authenticated-orcid":false,"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"H\u00f4pital Universitaire Necker\u2013Enfants Malades, Service de Neurologie P\u00e9diatrique, Centre de R\u00e9f\u00e9rence \u00c9pilepsies Rares, Imagine Institute, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unite Mixt\u00e9 de Recherche 1163, Paris Descartes University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail M.","family":"Farfel","sequence":"additional","affiliation":[{"name":"Zogenix, Inc.  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