{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:04:20Z","timestamp":1790417060456,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The orexin system is involved in anxiety behaviour and corresponding physiological reactions and constitutes a target for treatment of anxiety disorders. ACT\u2010539313 is a potent, selective orexin\u20101 receptor antagonist being developed for the treatment of anxiety disorders. This first\u2010in\u2010human study investigated its single\u2010dose pharmacokinetics (PK) including food effect, pharmacodynamics (PD), safety and tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This double\u2010blind, placebo\u2010controlled, randomized study included 40 healthy male subjects. Ascending oral doses of 10\u2013400 mg ACT\u2010539313 were investigated in 5 dose groups of 8 subjects (of whom 2 received placebo per dose group). At 100 mg, subjects received ACT\u2010539313 in fasted and fed conditions in a fixed sequential design. PK, PD (objective and subjective measures of sedation and effects on central nervous system), safety and tolerability were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In fasted conditions, ACT\u2010539313 was rapidly absorbed (median time to maximum plasma concentration [C<jats:sub>max<\/jats:sub>] 0.7\u20133.5 h) and cleared from plasma with a mean terminal half\u2010life of 3.3\u20135.7 h across dose levels. A 1.63\u2010fold (90% confidence interval: 1.26\u20132.11) increase in C<jats:sub>max<\/jats:sub> and no change in area under the concentration\u2013time curve extrapolated to infinity was observed under fed compared to fasted conditions. No relevant PD signals were detected except for a trend of reduced saccadic peak velocity around time to C<jats:sub>max<\/jats:sub>. The most commonly reported adverse events were somnolence and headache. All adverse events were transient and of mild or moderate intensity. No treatment\u2010related effects on vital signs, clinical laboratory or 12\u2010lead electrocardiogram were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ACT\u2010539313 exhibits good safety and tolerability at single doses of up to and including 400 mg that warrant further investigations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14251","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T03:09:10Z","timestamp":1581995350000},"page":"1377-1386","source":"Crossref","is-referenced-by-count":26,"title":["First\u2010in\u2010human study with ACT\u2010539313, a novel selective orexin\u20101 receptor antagonist"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2415-3012","authenticated-orcid":false,"given":"Priska","family":"Kaufmann","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil 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