{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T01:03:57Z","timestamp":1784423037961,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T00:00:00Z","timestamp":1708732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Staccato<jats:sup>\u00ae<\/jats:sup> alprazolam is a single\u2010use, drug\u2013device combination delivering alprazolam to the deep lung that is being evaluated as treatment for rapid and early seizure termination. This article reports pharmacokinetic (PK) data from two phase 1 studies of Staccato alprazolam in healthy adult participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The smoker study (EPK\u2010002\/NCT03516305) was an open\u2010label, nonrandomized, single\u2010dose, PK study in smokers and nonsmokers aged 21\u201350\u2009years, administered a single inhaled dose of 1\u2009mg Staccato alprazolam. The ethnobridging study (UP0101\/NCT04782388) was a double\u2010blind, placebo\u2010controlled study in Japanese, Chinese, and Caucasian participants aged 18\u201355\u2009years randomized 4:1 to a single inhaled dose of Staccato alprazolam 2\u2009mg or Staccato placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the smoker study, 36 participants (18 smokers, 18 nonsmokers) were enrolled and received Staccato alprazolam. Following Staccato administration, alprazolam was rapidly absorbed, with a median time to peak drug plasma concentration (<jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub>) of 2\u2009min in both smokers (range\u2009=\u20092\u201330\u2009min) and nonsmokers (range\u2009=\u20092\u201360\u2009min). Staccato alprazolam was rapidly absorbed to a similar extent in both smokers and nonsmokers. The most commonly reported treatment\u2010emergent adverse events (TEAEs) were somnolence and dizziness. In the ethnobridging study, 10 participants each of Japanese, Chinese, and Caucasian ethnicities were randomized 4:1 to Staccato alprazolam or Staccato placebo. Following Staccato administration, alprazolam was rapidly absorbed and distributed, with a median <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> of 1.5\u20132\u2009min in Japanese (range\u2009=\u20091\u20132\u2009min), Chinese (range\u2009=\u20091\u201334\u2009min), and Caucasian (range\u2009=\u20091\u2013120\u2009min) participants. Somnolence and sedation were the most commonly reported TEAEs. In both studies, there were no deaths, and no participants reported serious or severe TEAEs, or discontinued due to TEAEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Alprazolam was rapidly absorbed, and therapeutic drug levels were achieved within 2\u2009min postdose when administered to the lung with the Staccato device. Staccato alprazolam was generally well tolerated and displayed a safety profile consistent with that known from other alprazolam applications. No new safety signals were identified.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17901","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T11:04:37Z","timestamp":1708772677000},"page":"887-899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetics of Staccato<sup>\u00ae<\/sup> alprazolam in healthy adult participants in two phase 1 studies: An open\u2010label smoker study and a randomized, placebo\u2010controlled ethnobridging study"],"prefix":"10.1111","volume":"65","author":[{"given":"Yoshinobu","family":"Hayakawa","sequence":"first","affiliation":[{"name":"UCB Pharma  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Rospo","sequence":"additional","affiliation":[{"name":"UCB Pharma  Braine\u2010l'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Bartmann","sequence":"additional","affiliation":[{"name":"UCB Pharma  Braine\u2010l'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliceson","family":"King","sequence":"additional","affiliation":[{"name":"UCB Pharma  Smyrna Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Roebling","sequence":"additional","affiliation":[{"name":"UCB Pharma  Monheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-9813","authenticated-orcid":false,"given":"Hugues","family":"Chanteux","sequence":"additional","affiliation":[{"name":"UCB Pharma  Braine\u2010l'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2020.100409"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081754"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13121"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14479"},{"key":"e_1_2_13_6_1","volume-title":"Staccato\u00ae One Breath Technology","author":"Alexza Pharmaceuticals","year":"2023"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17441"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16279"},{"key":"e_1_2_13_9_1","unstructured":"University of Washington.Drug interaction solutions. 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