{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:52:41Z","timestamp":1789707161599,"version":"4.0.1"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Alprazolam administered via the Staccato\u00ae breath\u2010actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE\u2010E\u2010001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult patients with established diagnosis of focal and\/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double\u2010blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0\u00a0mg or 2.0\u00a0mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2\u00a0min after administration of study drug and no recurrence of seizure activity within 2\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double\u2010blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a038; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0392) and 2.0\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a038; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0392), compared with 42.5% for Staccato placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a040). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0\u00a0mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment\u2010related serious AEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Both 1.0\u00a0mg and 2.0\u00a0mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17441","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T09:59:35Z","timestamp":1666346375000},"page":"374-385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato\u00ae alprazolam for rapid seizure termination"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline","family":"French","sequence":"first","affiliation":[{"name":"New York University Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Biton","sequence":"additional","affiliation":[{"name":"Arkansas Epilepsy Program  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Dave","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Detyniecki","sequence":"additional","affiliation":[{"name":"University of Miami  Coral Gables Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Gelfand","sequence":"additional","affiliation":[{"name":"University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gong","sequence":"additional","affiliation":[{"name":"Rancho Los Amigos National Rehabilitation Center  Downey California 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"}]},{"given":"Terence J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Monash University and Alfred Hospital  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Sadek","sequence":"additional","affiliation":[{"name":"Research Institute of Orlando, LLC  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bree","family":"DiVentura","sequence":"additional","affiliation":[{"name":"The Epilepsy Study Consortium  Woodbury New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Reich","sequence":"additional","affiliation":[{"name":"Engage Therapeutics, Inc.  Summit New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouko","family":"Isojarvi","sequence":"additional","affiliation":[{"name":"Engage Therapeutics, Inc.  Summit New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Valeant Pharmaceuticals North America LLC.Diastat C\u2010IV (diazepam rectal gel) rectal delivery system prescribing information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/020648s014lbl.pdf(2016). Accessed 2 Mar 2022."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-5050(02)00559-0"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2017.02.023"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12755"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081754"},{"key":"e_1_2_11_7_1","unstructured":"Pfizer.XANAX\u00ae alprazolam tablets USP prescribing information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/018276s045lbl.pdf(2011). Accessed 2 Mar 2022."},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16279"},{"key":"e_1_2_11_9_1","first-page":"1121","article-title":"Ro 19\u20108022, a nonbenzodiazepine partial agonist at benzodiazepine receptors: neuropharmacological profile of a potential anxiolytic","volume":"262","author":"Jenck F","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.14712\/18059694.2020.35"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(95)02147-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.77.483"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2020.100409"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.316"},{"key":"e_1_2_11_15_1","unstructured":"ClinicalTrials.gov.A study to test the efficacy and safety of Staccato alprazolam in study participants 12\u2009years of age and older with stereotypical prolonged seizures (NCT05077904).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05077904. Accessed 2 Mar 2022."}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17441","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.17441","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17441","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T23:34:57Z","timestamp":1692574497000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,7]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/epi.17441"],"URL":"https:\/\/doi.org\/10.1111\/epi.17441","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,7]]},"assertion":[{"value":"2022-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}