{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:51:08Z","timestamp":1794009068124,"version":"4.8.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Millennium Pharmaceuticals Inc"},{"name":"Takeda Development Center Americas, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objectives<\/jats:title><jats:p>Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug\/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adults with IH aged 18\u201375 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH.<\/jats:p><jats:p>Clinical Trial: Clinicaltrials.gov. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04091438<\/jats:p><\/jats:sec>","DOI":"10.1093\/sleep\/zsad049","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T10:46:27Z","timestamp":1678272387000},"source":"Crossref","is-referenced-by-count":17,"title":["Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6928-5310","authenticated-orcid":false,"given":"Emmanuel","family":"Mignot","sequence":"first","affiliation":[{"name":"Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University Medical School , Palo Alto, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7043-2974","authenticated-orcid":false,"given":"Richard K","family":"Bogan","sequence":"additional","affiliation":[{"name":"Bogan Sleep Consultants, LLC , Columbia, SC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Emsellem","sequence":"additional","affiliation":[{"name":"The Center of Sleep & Wake Disorders , Chevy Chase, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Foldvary-Schaefer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sleep Disorders Center, Cleveland Clinic , Cleveland, OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Naylor","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc., Lexington , MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Neuwirth","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc., Lexington , MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Faessel","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc., Lexington , MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Swick","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc., Lexington , MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Olsson","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc., Lexington , MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"issue":"1","key":"2023090806302003200_CIT0001","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1474-4422(21)00368-9","article-title":"Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study","volume":"21","author":"Dauvilliers","year":"2022","journal-title":"Lancet Neurol."},{"issue":"1","key":"2023090806302003200_CIT0002","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s13311-020-00919-1","article-title":"Idiopathic hypersomnia and other hypersomnia syndromes","volume":"18","author":"Trotti","year":"2021","journal-title":"Neurotherapeutics"},{"issue":"6","key":"2023090806302003200_CIT0003","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/01616412.2017.1315864","article-title":"A review of sleep disorders and melatonin","volume":"39","author":"Xie","year":"2017","journal-title":"Neurol Res."},{"key":"2023090806302003200_CIT0004","volume-title":"International Classification of Sleep Disorders","author":"American Academy of Sleep Medicine","year":"2014","edition":"- Third Edition"},{"key":"2023090806302003200_CIT0005","article-title":"Assessment of sleep disorders and diagnostic procedures. 1. 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