{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:26Z","timestamp":1787014166306,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy \u22656\u00a0years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A long\u2010term, phase 3, open\u2010label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6\u201365\u00a0years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144\/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41\/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no\u2010benzodiazepine group. Findings were similar in a sub\u2010analysis of patients who were (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a044) or were not (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a075) taking clobazam.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This analysis of patients from a long\u2010term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub\u2010analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16901","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T03:11:40Z","timestamp":1620097900000},"page":"1442-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long\u2010term, open\u2010label safety study"],"prefix":"10.1111","volume":"62","author":[{"given":"Eric B.","family":"Segal","sequence":"first","affiliation":[{"name":"Hackensack University Medical Center, Hackensack Meridian School of Health, and Northeast Regional Epilepsy Group Hackensack NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Tarquinio","sequence":"additional","affiliation":[{"name":"Center for Rare Neurological Diseases Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-1015","authenticated-orcid":false,"given":"Ian","family":"Miller","sequence":"additional","affiliation":[{"name":"Nicklaus Children's Hospital Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Wheless","sequence":"additional","affiliation":[{"name":"Le Bonheur Children's Hospital University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Dlugos","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Biton","sequence":"additional","affiliation":[{"name":"Arkansas Epilepsy Program Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Cascino","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Desai","sequence":"additional","affiliation":[{"name":"Children's Hospital of Los Angeles Los Angeles CA 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 MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kore","family":"Liow","sequence":"additional","affiliation":[{"name":"Hawaii Pacific Neuroscience Honolulu HI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-6006","authenticated-orcid":false,"given":"Michael R.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Cook","sequence":"additional","affiliation":[{"name":"Neurelis, Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis, Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis, Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The DIAZ.001.05 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1965.tb03786.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn037"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000177"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0000000000000140"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.87.3.225"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7597-16.1.48"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602537808993775"},{"key":"e_1_2_9_10_1","first-page":"214","article-title":"Benzodiazepine pharmacology and central nervous system\u2010mediated effects","volume":"13","author":"Griffin CE","year":"2013","journal-title":"Ochsner J"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.15159"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2000.tb00128.x"},{"key":"e_1_2_9_13_1","unstructured":"Valeant Pharmaceuticals.Diastat\u00ae(diazepam rectal gel).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/020648s014lbl.pdf. Accessed 22 July 2020."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806253382602"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.07.001"},{"key":"e_1_2_9_16_1","unstructured":"Neurelis Inc.VALTOCO\u00ae(diazepam nasal spray).https:\/\/www.valtoco.com\/sites\/default\/files\/Prescribing_Information.pdf. Accessed 22 July 2020."},{"key":"e_1_2_9_17_1","unstructured":"UCB Inc.NAYZILAM\u00ae(midazolam) nasal spray.https:\/\/www.ucb\u2010usa.com\/_up\/ucb_usa_com_kopie\/documents\/Nayzilam_PI.pdf. Accessed 22 July 2020."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16449"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16506"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2013.02.018"},{"key":"e_1_2_9_21_1","unstructured":"US Food and Drug Administration. Clinical superiority findings. Available at:https:\/\/www.fda.gov\/industry\/designating\u2010orphan\u2010product\u2010drugs\u2010and\u2010biological\u2010products\/clinical\u2010superiority\u2010findings. Accessed 23 June 2020."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-012-0069-z"},{"key":"e_1_2_9_23_1","volume-title":"Onfi\u00ae (clobazam). Full Prescribing Information","author":"Lundbeck","year":"2021"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.01.025"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16300"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-016-0401-x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb02047.x"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16901","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16901","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16901","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T23:07:53Z","timestamp":1693350473000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/epi.16901"],"URL":"https:\/\/doi.org\/10.1111\/epi.16901","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"assertion":[{"value":"2020-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}