{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:05:04Z","timestamp":1783955104036,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100024157","name":"Neurelis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100024157","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Seizure clusters, intermittent increases in seizure activity that differ from a patient's usual seizure pattern, may occur despite treatment with a daily anti\u2010seizure medication. Benzodiazepine\u2010containing immediate\u2010use seizure medications (ISMs; also called rescue therapies) are the cornerstone of treatment for seizure clusters. Diazepam nasal spray is approved by the U.S. Food and Drug Administration to treat seizure clusters in patients with epilepsy \u22652\u2009years of age. A prior long\u2010term safety study of diazepam nasal spray showed an increased inter\u2010seizure cluster interval (SEIzure interVAL [SEIVAL]) in days across a year in patients 6 to 65\u2009years of age. The current analysis focused on changes in SEIVAL over time in a separate study in children with epilepsy 2 to 5\u2009years of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with epilepsy 2 to 5\u2009years of age were enrolled in an open\u2010label, Phase 1\/2a trial of diazepam nasal spray that included a single\u2010dose pharmacokinetics period, 180\u2010day safety period, and optional extension period. Doses of 5, 10, or 15\u2009mg were administered based on weight (0.5\u2009mg\/kg). A post hoc analysis evaluated SEIVAL for consecutive 90\u2010day periods overall and in a consistent cohort of patients with persistent use and SEIVALs in each period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among enrolled patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936), 22 (61.1%) had \u22651 SEIVAL, with a total of 315 SEIVALs recorded. Mean SEIVAL (\u00b1SD) doubled from 25.2 (\u00b121.3) days in Period 1 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920) to 51.9 (\u00b172.4) days in Period 3 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098). In the consistent cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097), mean SEIVAL increased from 22.1 (\u00b112.7) days in Period 1 to 27.7 (\u00b125.4) days in Period 3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These results corroborate those of the earlier post hoc analysis of data from patients 6 to 65\u2009years of age who received diazepam nasal spray for seizure clusters. These findings suggest a beneficial long\u2010term treatment effect of diazepam nasal spray beyond acute use as an ISM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70256","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:21:22Z","timestamp":1778167282000},"page":"3471-3478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased interval between seizure clusters across time in pediatric patients treated with the immediate\u2010use seizure medication diazepam nasal spray"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-3431","authenticated-orcid":false,"given":"James W.","family":"Wheless","sequence":"first","affiliation":[{"name":"Le Bonheur Children's Hospital University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-6394","authenticated-orcid":false,"given":"Eric","family":"Segal","sequence":"additional","affiliation":[{"name":"Hackensack University Medical Center and Northeast Regional Epilepsy Group and Hackensack Meridian School of Medicine  Hackensack New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-2814","authenticated-orcid":false,"given":"Jurriaan M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Harvard Medical School and Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7602-3474","authenticated-orcid":false,"given":"Steven M.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Boston Children's Health Physicians  New York USA"},{"name":"Department of Neurology Westchester Medical Center  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genei","family":"Bougher","sequence":"additional","affiliation":[{"name":"Northwest Florida Clinical Research Group  Gulf Breeze Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Davis","sequence":"additional","affiliation":[{"name":"CSD Biostatistics, Inc.  Oro Valley Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-1367","authenticated-orcid":false,"given":"Leock Y.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-0722","authenticated-orcid":false,"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"},{"name":"John A. Burns School of Medicine University of Hawaii  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-0606","authenticated-orcid":false,"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"},{"name":"Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science Florida Atlantic University  Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107836"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0000000000000140"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272\u2010023\u201000601\u2010x"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S481758"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010023\u201000568\u20104"},{"key":"e_1_2_15_8_1","volume-title":"Diastat\u00ae C\u2010IV (diazepam rectal gel). Full Prescribing Information","author":"Bausch Health US, LLC","year":"2023"},{"key":"e_1_2_15_9_1","volume-title":"VALTOCO\u00ae (diazepam nasal spray). Full Prescribing Information","author":"Neurelis, Inc","year":"2025"},{"key":"e_1_2_15_10_1","volume-title":"Nayzilam\u00ae (midazolam nasal spray). Full Prescribing Information","author":"UCB, Inc","year":"2023"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806253382602"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.15159"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17041"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17385"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18473"},{"key":"e_1_2_15_16_1","unstructured":"SperlingMR PetersJM DavisCS RabinowiczAL CarrazanaE.Is disease modification in seizure clusters possible? Results from the long\u2010term safety study of diazepam nasal spray. Presented at: American Epilepsy Society 2024 Annual Meeting December 6\u201310 2024; Los Angeles CA."},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107983"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2019.00223"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2007.10.010"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12954"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13092258"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi.70051"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.02.002"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild\u20102019\u2010318676"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70256","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:15:00Z","timestamp":1783952100000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/epi.70256"],"URL":"https:\/\/doi.org\/10.1002\/epi.70256","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]},"assertion":[{"value":"2025-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}