{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:56:12Z","timestamp":1791640572344,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Eisai Inc. Medical"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lemborexant, a dual orexin receptor antagonist, is approved for the treatment of insomnia and is under investigation for treating other sleep disorders. Here we summarize pharmacokinetic, pharmacodynamic, and safety data from 3 randomized, double\u2010blind, placebo\u2010controlled phase 1 studies: single ascending doses in healthy adults (Study 001; 1\u2010200\u00a0mg; N\u00a0=\u00a064), multiple ascending doses in healthy and elderly adults (Study 002; 2.5\u201075\u00a0mg; N\u00a0=\u00a055), and multiple doses in healthy white and Japanese adults (Study 003; 2.5\u201025\u00a0mg; N\u00a0=\u00a032). Lemborexant exposure increased with increasing dose. The time to maximum concentration ranged from approximately 1 to 3 hours for the 5\u2010 and 10\u2010mg doses. The mean effective half\u2010life was 17 hours for lemborexant 5\u00a0mg and 19 hours for lemborexant 10\u00a0mg. The plasma concentration at 9 hours postdose was 27% of the maximum concentration following multiple dosing with lemborexant 10\u00a0mg. There were no clinically relevant effects on next\u2010morning residual sleepiness (Karolinska Sleepiness Scale, Digital Symbol Substitution Test, Psychomotor Vigilance Test) for doses through 10\u00a0mg\/day, indicating no effect of residual plasma concentrations on next\u2010day residual effects. Lemborexant was well tolerated across the doses tested. There were no clinically relevant effects of age, sex, or race on lemborexant pharmacokinetics, pharmacodynamics, or safety. These results suggest that lemborexant at doses through 25\u00a0mg provides an overall pharmacokinetic, pharmacodynamic, and safety profile suitable for obtaining the target pharmacologic effect supporting treatment of insomnia while minimizing residual effects during wake time.<\/jats:p>","DOI":"10.1002\/cpdd.817","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:05:10Z","timestamp":1590710710000},"page":"153-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Pharmacokinetics, Pharmacodynamics, and Safety of the Dual Orexin Receptor Antagonist Lemborexant: Findings From Single\u2010Dose and Multiple\u2010Ascending\u2010Dose Phase 1 Studies in Healthy Adults"],"prefix":"10.1002","volume":"10","author":[{"given":"Ishani","family":"Landry","sequence":"first","affiliation":[{"name":"Eisai Inc Woodcliff Lake  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenya","family":"Nakai","sequence":"additional","affiliation":[{"name":"Eisai Co, Ltd, Koishikawa  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Ferry","sequence":"additional","affiliation":[{"name":"Eisai Inc Woodcliff Lake  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagadeesh","family":"Aluri","sequence":"additional","affiliation":[{"name":"Eisai Inc Woodcliff Lake  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hall","sequence":"additional","affiliation":[{"name":"Eisai Inc Woodcliff Lake  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojan","family":"Lalovic","sequence":"additional","affiliation":[{"name":"Eisai Inc Woodcliff Lake  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L.","family":"Moline","sequence":"additional","affiliation":[{"name":"Eisai Inc Woodcliff Lake  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2017.03.015"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010510-100528"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.04.007"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2016.12.008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.18254"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.6800"},{"key":"e_1_2_11_9_1","unstructured":"YardleyJ PinnerK MurphyP FilippovG ZammitG MolineM.Efficacy of lemborexant compared with placebo in adult and elderly subjects with insomnia: results from a phase 3 study (SUNRISE\u20102). Presented at: Advances in Sleep and Circadian Science\/Sleep Research Society; February 1\u20104 2019; Clearwater Beach FL."},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00217"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2018.1482509"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.241422"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz076"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04117.x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199203000-00003"},{"key":"e_1_2_11_16_1","unstructured":"LalovicB MajidO LandryI et\u00a0al.Population pharmacokinetics of lemborexant a dual orexin receptor antagonist in healthy adult and elderly subjects and subjects with primary insomnia. Presented at: Annual Meeting of the Population Approach Group in Europe; June 11\u201014 2019; Stockholm Sweden."},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207459008994241"},{"key":"e_1_2_11_18_1","volume-title":"Manual for the Wechsler Adult Intelligence Scale, Revised","author":"Wechsler D.","year":"1981"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1417.002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1076\/jcen.20.3.310.823"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.785"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-14-90"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsy260"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1544"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.10.003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70053-5"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.817","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.817","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.817","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T14:47:18Z","timestamp":1693752438000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,28]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/cpdd.817"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.817","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,28]]},"assertion":[{"value":"2020-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}