{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:54:09Z","timestamp":1788792849335,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. We report results from the first two randomised, double\u2010blind clinical studies of daridorexant in Japanese subjects. In the Phase 1 study, daridorexant (10, 25, 50\u2009mg) or placebo were administered in the morning for 4\u2009days in 24 young (mean age 26.9\u2009years) and 24 older (mean age 69.7\u2009years) healthy Japanese adults. Daridorexant reached a peak plasma concentration within 1.0\u2009h across every dose and age group. For all doses, the mean plasma concentration of daridorexant showed a similar change between the age groups. Exposure parameters increased dose\u2010dependently with minimal\/no accumulation upon repeated dosing. The terminal half\u2010life was ~8\u2009h. In the Phase 2, four\u2010period, four\u2010way crossover study, 47 Japanese subjects (mean age 50.4\u2009years) with insomnia disorder were randomised to receive four treatments (daridorexant 10, 25, 50\u2009mg, placebo) during four treatment periods, each consisting of two treatment nights (5\u201312 day washout between treatment periods). Subjects continued their fourth treatment for 12 further days. A statistically significant dose\u2013response relationship (multiple\u2010comparison procedure\u2010modelling, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) was found in the reduction of polysomnography\u2010measured wake after sleep onset (WASO; primary endpoint) and latency to persistent sleep (secondary endpoint) from baseline to days 1\/2. Statistically significant dose\u2013response relationships were also observed for secondary subjective endpoints from baseline to days 1\/2 (sWASO, latency to sleep onset). All daridorexant doses were well tolerated, with no treatment discontinuations and no next\u2010morning residual effects. These results supported further investigation of daridorexant in Japanese patients with insomnia disorder.<\/jats:p>","DOI":"10.1111\/jsr.14302","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T04:31:03Z","timestamp":1723177863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies"],"prefix":"10.1111","volume":"34","author":[{"given":"Makoto","family":"Uchiyama","sequence":"first","affiliation":[{"name":"Department of Psychiatry Nihon University School of Medicine  Tokyo Japan"},{"name":"Tokyo Adachi Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Akita University Graduate School of Medicine  Akita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Yagi","sequence":"additional","affiliation":[{"name":"Kurume University School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"SOUSEIKAI Fukuoka Mirai Hospital Clinical Research Center  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Eto","sequence":"additional","affiliation":[{"name":"SOUSEIKAI Hakata Clinic  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-3788","authenticated-orcid":false,"given":"Clemens","family":"Muehlan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Togo","sequence":"additional","affiliation":[{"name":"Data Management &amp; Biometry, Nxera Pharma Japan Co., Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7414-9017","authenticated-orcid":false,"given":"Yuichi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Yoyogi Sleep Disorder Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182412976"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2005.00344.x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1544"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200847050-00002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2011.07.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170772"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544010-00002"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25680"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527320666210618103344"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-023-01020-9"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-022-00977-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-clinpsy-032813-153716"},{"key":"e_1_2_12_15_1","first-page":"214","article-title":"Benzodiazepine pharmacology and central nervous system\u2010mediated effects","volume":"13","author":"Griffin C. 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