{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:59:21Z","timestamp":1773071961051,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015693","name":"Purdue Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005612","name":"Shionogi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Sunobinop is a novel, potent, selective partial agonist at nociceptin\/orphanin FQ peptide (NOP) receptors. The primary objective of this randomized, double-blind, placebo-controlled study was to assess the next-day residual effects of an evening dose of sunobinop in healthy participants. Participants were randomized into 1 of 5 treatment sequences. Treatment consisted of 1 dose each of sunobinop 0.2, 0.6, 2, and 6\u00a0mg suspension and placebo suspension. Key pharmacodynamic (PD) measures included the digit symbol substitution test (DSST), Karolinska sleepiness scale (KSS), and body sway. The randomized safety population consisted of 25 participants. The DSST, KSS, and body sway showed dose-dependent effects following the administration of sunobinop, with no significant differences versus placebo at sunobinop doses &amp;lt;2\u00a0mg. At sunobinop 2\u00a0mg, PD effects were relatively small in magnitude and inconsistent. The last timepoint where significant differences between sunobinop 2\u00a0mg and placebo on the DSST, KSS, and body sway were observed was at 12\u00a0h, 16.5\u00a0h, and 13.5\u00a0h postdose, respectively. Sunobinop 6\u00a0mg resulted in larger and consistent PD effects, with significant differences from placebo at all timepoints up to 16.5\u201318\u00a0h postdose. Somnolence was the most frequently reported adverse event (AE), and all AEs were mild-to-moderate. No deaths occurred during the study or discontinuations due to an AE. Overall, a nighttime oral dose of sunobinop up to 2\u00a0mg was safe and generally well tolerated in healthy participants with limited next-day residual effects that were consistent with other sedative\/hypnotic drugs.<\/jats:p>","DOI":"10.3389\/fphar.2024.1432902","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T08:24:23Z","timestamp":1724055863000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of sunobinop for next-day residual effects in healthy participants"],"prefix":"10.3389","volume":"15","author":[{"given":"Alessandra","family":"Cipriano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram P.","family":"Kapil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjunath S.","family":"Shet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen","family":"Apseloff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garth T.","family":"Whiteside","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/jsr.12158","article-title":"Subjective sleepiness is a sensitive indicator of insufficient sleep and impaired waking function","volume":"23","author":"Akerstedt","year":"2014","journal-title":"J. Sleep. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3109\/00207459008994241","article-title":"Subjective and objective sleepiness in the active individual","volume":"52","author":"Akerstedt","year":"1990","journal-title":"Int. J. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1111\/jsr.12528","article-title":"Normative data on the diurnal pattern of the Karolinska Sleepiness Scale ratings and its relation to age, sex, work, stress, sleep quality and sickness absence\/illness in a large sample of daytime workers","volume":"26","author":"Akerstedt","year":"2017","journal-title":"J. Sleep. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1097\/j.pain.0000000000000597","article-title":"Nociceptin\/orphanin FQ receptor expression in clinical pain disorders and functional effects in cultured neurons","volume":"157","author":"Anand","year":"2016","journal-title":"Pain"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"Association","year":"2013"},{"key":"B6","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1097\/00004714-199304000-00003","article-title":"Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects","volume":"13","author":"Berlin","year":"1993","journal-title":"J. Clin. Psychopharmacol."},{"key":"B7","article-title":"Zolpidem","volume-title":"StatPearls [Internet]","author":"Bouchette","year":"2024"},{"key":"B8","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1002\/cpdd.1394","article-title":"Safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of sunobinop in healthy participants","volume":"13","author":"Cipriano","year":"2024","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1097\/JCP.0000000000000941","article-title":"Digit symbol substitution test: the case for sensitivity over specificity in neuropsychological testing","volume":"38","author":"Jaeger","year":"2018","journal-title":"J. Clin. Psychopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1080\/00325481.2017.1249265","article-title":"A review of trazodone use in psychiatric and medical conditions","volume":"129","author":"Khouzam","year":"2017","journal-title":"Postgrad. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nrd2572","article-title":"The nociceptin\/orphanin FQ receptor: a target with broad therapeutic potential","volume":"7","author":"Lambert","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"B12","doi-asserted-by":"publisher","first-page":"765","DOI":"10.5664\/jcsm.8294","article-title":"Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening","volume":"16","author":"Murphy","year":"2020","journal-title":"J. Clin. Sleep. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1111\/j.1365-2869.2011.00928.x","article-title":"Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs","volume":"20","author":"Roth","year":"2011","journal-title":"J. Sleep. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"259","DOI":"10.5665\/sleep.2386","article-title":"Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men","volume":"36","author":"Sun","year":"2013","journal-title":"Sleep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1097\/00004714-200006000-00007","article-title":"Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance","volume":"20","author":"Troy","year":"2000","journal-title":"J. Clin. Psychopharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/npr2.12262","article-title":"Residual effects of low dose of suvorexant, zolpidem, and ramelteon in healthy elderly subjects: a randomized double-blind study","volume":"42","author":"Uemura","year":"2022","journal-title":"Neuropsychopharmacol. Rep."},{"key":"B17","volume-title":"Manual for the wechsler adult Intelligence scale, revised","author":"Wechsler","year":"1981"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e171172","DOI":"10.1172\/JCI171172","article-title":"The nociceptin\/orphanin FQ receptor partial agonist sunobinop promotes non-REM sleep in rodents and patients with insomnia. J Clin Invest","volume":"134","author":"Whiteside","year":"2024","journal-title":"J. Clin. Invest."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e152","DOI":"10.1097\/ju.0000000000003229.09","article-title":"PD05-09: effects of sunobinop (V117957) in a model of acute cystitis induced by cyclophosphamide","volume":"209","author":"Whiteside","year":"2023","journal-title":"J. Urology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.pharmthera.2013.10.011","article-title":"The biology of Nociceptin\/Orphanin FQ (N\/OFQ) related to obesity, stress, anxiety, mood, and drug dependence","volume":"141","author":"Witkin","year":"2014","journal-title":"Pharmacol. Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1432902\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T08:24:28Z","timestamp":1724055868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1432902\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":20,"alternative-id":["10.3389\/fphar.2024.1432902"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1432902","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,19]]},"article-number":"1432902"}}