{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:49:48Z","timestamp":1792496988498,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Fazamorexant is a dual orexin receptor antagonist being developed for the treatment of insomnia. This study aims to determine the dose\u2010exposure\u2010response relationship of single\u2010dose fazamorexant\n                      <jats:italic>vs<\/jats:italic>\n                      . zolpidem in young adult and elderly healthy Chinese volunteers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single\u2010centre, randomized, double\u2010blind, double\u2010dummy, placebo\u2010 and active\u2010controlled, 4\u2010period crossover study administered fazamorexant (40\u2009mg\/80\u2009mg to young adults; 20\u2009mg\/40\u2009mg to the elderly) and zolpidem (10\u00a0mg). Pharmacokinetics, pharmacodynamics (primary endpoint: SPV) and safety were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following a single 40\u202fmg oral dose of fazamorexant in elderly and young adults, the geometric least\u2011squares mean (GLSM) values for C\n                      <jats:sub>max<\/jats:sub>\n                      were 1527.05\u202fng\/mL (95% CI: 1268.66\u20131838.06) in the elderly and 1652.52\u202fng\/mL (95% CI: 1420.41\u20131922.56) in young adults. The corresponding GLSM AUC\n                      <jats:sub>0\u2013t<\/jats:sub>\n                      values were 7815.91\u202fh\u00b7ng\/mL (95% CI: 5985.56\u201310205.97) and 8351.15\u202fh\u00b7ng\/mL (95% CI: 6716.38\u201310383.84), respectively. There was no significant pharmacokinetic difference between young adults and the elderly with fazamorexant (C\n                      <jats:sub>max<\/jats:sub>\n                      GMR 92.41% [90% CI: 75.84\u2013112.59]; AUC\n                      <jats:sub>0\u2010t<\/jats:sub>\n                      GMR 93.59% [90% CI: 70.43\u2013124.37]). In general, high\u2010dose fazamorexant caused similar or less impairment\n                      <jats:italic>vs<\/jats:italic>\n                      . zolpidem in eye movements (SPV: young adults: 110.4\u2009\u00b1\u200980.1\n                      <jats:italic>vs<\/jats:italic>\n                      . 108.3\u2009\u00b1\u200982.7\u00a0deg\/sec\uff1belderly: 145.1\u2009\u00b1\u200964.2\n                      <jats:italic>vs<\/jats:italic>\n                      . 185.5\u2009\u00b1\u200963.0\u00a0deg\/sec), choice\u2010reaction\u2010time performance, body sway and memory tests in young and elderly cohorts. The effects of low\u2010dose fazamorexant on these psychomotor and cognitive measurements were significantly smaller than those of high\u2010dose fazamorexant and zolpidem in both age cohorts. Despite of similarity in exposure, fazamorexant demonstrated larger effects on the pharmacodynamic measurements in the elderly than in young adults, suggesting an age\u2010related increase of pharmacological sensitivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clinically hypnotic doses of fazamorexant induced less balance, judgement and memory impairment in healthy adults and elderly volunteers compared to the comprehensive suppression of zolpidem on the neurological system. These preliminary results suggest that fazamorexant is a potentially safer drug for insomnia. No age\u2010related pharmacokinetic difference was identified with fazamorexant.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70414","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:26:11Z","timestamp":1768872371000},"page":"1473-1486","source":"Crossref","is-referenced-by-count":1,"title":["Hypnotic doses of fazamorexant induced less impairment on balance and cognition than zolpidem in healthy younger and elderly individuals"],"prefix":"10.1002","volume":"92","author":[{"given":"Chen","family":"Xia","sequence":"first","affiliation":[{"name":"Phase I Unit, Beijing Tiantan Hospital, Capital Medical University  Beijing 100050 China"},{"name":"Hangzhou Tigermed Consulting Co., Ltd.  Hangzhou 310051 Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Xingxing","sequence":"additional","affiliation":[{"name":"Yangtze River Pharmaceutical Group Co, Ltd.  Taizhou 225300 Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Lu","sequence":"additional","affiliation":[{"name":"Yangtze River Pharmaceutical Group Co, Ltd.  Taizhou 225300 Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Ruwei","sequence":"additional","affiliation":[{"name":"Yangtze River Pharmaceutical Group Co, Ltd.  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