{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:32:27Z","timestamp":1792517547041,"version":"4.5.0"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"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":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>An exploratory analysis from a long\u2010term, phase 3, open\u2010label, repeat\u2010dose safety study of diazepam nasal spray for acute treatment of seizure clusters assessed the use of a second dose up to 24\u00a0hours after the initial dose and effectiveness in potentially reducing the number of seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seizures and doses were recorded in diaries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 175 patients enrolled, 163 received \u22651 dose of diazepam nasal spray and were included in the safety population; those patients received a total of 4390 doses for a total of 3853\u00a0seizure clusters. Less than half of these patients used a second dose a least once during the study (79 patients [48.5%]), with a total of 485\u00a0second doses for seizure clusters (12.6% of all seizure clusters). Among these 79 patients, 33 (41.8%) used only one second dose during the study (range: 1\u201382). The proportion of seizure clusters treated with a second dose over time was consistently low across 24\u00a0h: 0\u20134\u00a0h, 152 (3.9%); 4\u20136\u00a0h, 72 (1.9%); 6\u20138\u00a0h, 39 (1.0%); 8\u201312\u00a0h, 55 (1.4%); 12\u201316\u00a0h, 42 (1.1%); 16\u201320\u00a0h, 42 (1.1%); 20\u201324\u00a0h, 83 (2.2%). Rates of treatment\u2010emergent adverse events (TEAEs) and treatment\u2010related TEAEs occurring within 1\u00a0day of a second dose were low (15.2% and 5.1%, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Patients with epilepsy may experience seizure clusters lasting up to 24\u00a0hours, and little is known about the effectiveness of rescue therapies for that duration. The current labeling of the US Food and Drug Administration (FDA)\u2013approved outpatient treatments for seizure clusters (rectal diazepam, intranasal midazolam, and diazepam nasal spray) allows for a second dose, if needed, for control. These findings support the safety profile of second doses, and the low use supports the effectiveness of diazepam nasal spray across 24\u00a0hours.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17177","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T23:19:53Z","timestamp":1643843993000},"page":"836-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Use of second doses of Valtoco\u00ae (diazepam nasal spray) across 24\u00a0hours after the initial dose for out\u2010of\u2010hospital seizure clusters: Results from a phase 3, open\u2010label, repeat\u2010dose safety study"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-6006","authenticated-orcid":false,"given":"Michael R.","family":"Sperling","sequence":"first","affiliation":[{"name":"Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-3431","authenticated-orcid":false,"given":"James W.","family":"Wheless","sequence":"additional","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\/0000-0003-2272-5005","authenticated-orcid":false,"given":"R. Edward","family":"Hogan","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Dlugos","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Cascino","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kore","family":"Liow","sequence":"additional","affiliation":[{"name":"Hawaii Pacific Neuroscience  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"}],"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"}]},{"name":"DIAZ 001.05 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.04.022"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0000000000000140"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb01607.x"},{"key":"e_1_2_9_6_1","volume-title":"Diastat\u00ae C\u2010IV (diazepam rectal gel). Full prescribing information","author":"Bausch Health US, LLC","year":"2021"},{"key":"e_1_2_9_7_1","volume-title":"NAYZILAM\u00ae (midazolam nasal spray). Full prescribing information","author":"UCB, Inc","year":"2021"},{"key":"e_1_2_9_8_1","volume-title":"Valtoco (diazepam nasal spray). Full prescribing information","author":"Neurelis, Inc","year":"2021"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17041"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1989.tb05819.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb02047.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2012.04.128"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17177","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.17177","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T23:13:36Z","timestamp":1692832416000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,2]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/epi.17177"],"URL":"https:\/\/doi.org\/10.1111\/epi.17177","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742023314.793592757","asserted-by":"object"}]},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,2]]},"assertion":[{"value":"2021-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}