{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:54:36Z","timestamp":1753869276802,"version":"3.41.2"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T00:00:00Z","timestamp":1576195200000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Psychopharmacology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objectives of this study were primarily to assess the efficacy and safety of SM\u20101 in a circadian challenge model of transient insomnia and secondarily, to assess the contribution of diphenhydramine to the combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Randomized, double\u2010blind, placebo\u2010controlled three\u2010way cross\u2010over study with a 5\u2010hr phase advance. Subjects were 39 healthy adults reporting a history of transient insomnia. All treatments (SM\u20101, SM\u20101 without diphenhydramine, or placebo) were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time (TST) determined by polysomnography. Secondary endpoints included wakefulness after sleep onset (WASO), latency to persistent sleep, number of awakenings (NAW), subjective TST (sTST) and sleep latency (sSL), TST, and NAW by quarters of the night and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale digit symbol substitution test, and subject\u2010reported alertness level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SM\u20101 provided an increase of 126.7 min in TST over placebo (<jats:italic>p<\/jats:italic> &lt; .001). WASO, sTST, sleep quality, and sSL also showed significant improvement. Diphenhydramine demonstrated a significant (<jats:italic>p<\/jats:italic> = .014) contribution of 43.7 min to TST. SM\u20101 was well\u2010tolerated with type and frequency of adverse events comparable with placebo, and no residual sleepiness upon awakening after 8 hr.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SM\u20101 provided a robust and statistically significant increase in TST compared with placebo in a circadian model of transient insomnia, without evidence of next\u2010day impairment. Diphenhydramine contributed to the effect.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hup.2713","type":"journal-article","created":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T07:46:08Z","timestamp":1576309568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of SM\u20101 in a transient insomnia model"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4642-4346","authenticated-orcid":false,"given":"Thomas","family":"Dahl","sequence":"first","affiliation":[{"name":"Sequential Medicine Ltd  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"Sequential Medicine Ltd  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Zammit","sequence":"additional","affiliation":[{"name":"Clinilabs Drug Development Corporation  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Clinilabs Drug Development Corporation  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Roth","sequence":"additional","affiliation":[{"name":"Sleep Disorders and Research Henry Ford Hospital Sleep Disorders Center  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"392","article-title":"Effect of diphenhydramine on subjective sleep parameters and on motor activity during bedtime","volume":"26","author":"Borb\u00e9ly A. 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