{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:02:23Z","timestamp":1787169743740,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Etrasimod is an investigational, once\u2010daily, oral, selective sphingosine 1\u2010phosphate receptor 1,4,5 modulator used as an oral treatment option for immune\u2010mediated inflammatory disorders. This randomized, double\u2010blind, placebo\u2010 and positive\u2010controlled, parallel\u2010group, healthy adult study investigated etrasimod's effect on the QT interval and other electrocardiogram parameters. All participants received etrasimod\u2010matched placebo on day 1. Group A received once\u2010daily, multiple ascending doses of etrasimod (2\u20104\u00a0mg) on days 1\u201014 and moxifloxacin\u2010matched placebo on days 1 and 15. Group\u00a0B received etrasimod\u2010matched placebo on days 1\u201014 and either moxifloxacin 400\u00a0mg or moxifloxacin\u2010matched placebo on days 1 and 15. The primary analysis was a concentration\u2010QTc analysis using a corrected QT interval by Fridericia (QTcF). The etrasimod concentration\u2010QTc analysis predicted placebo\u2010corrected change from baseline QTcF (\u0394\u0394QTcF) values and associated 90% confidence intervals remained &lt;10\u00a0milliseconds over the observed etrasimod plasma concentration range (\u2264279\u00a0ng\/mL). Etrasimod was associated with mild, transient, asymptomatic heart rate slowing that was most pronounced on day 1 (2\u00a0mg, first dose). The largest\u2010by\u2010time point mean placebo\u2010corrected changes in heart rate from time\u2010matched day \u22121 baseline (\u2206\u2206HR) on days 1, 7 (2\u00a0mg, last dose), and 14 (4\u00a0mg, last dose) were \u221215.1, \u22128.5, and \u22126.0\u00a0bpm, respectively. Etrasimod's effects on PR interval were small, with the largest least squares mean placebo\u2010corrected change from baseline in PR interval (\u2206\u2206PR) being 6.6\u00a0milliseconds. No episodes of atrioventricular block were observed. Thus, multiple ascending doses of etrasimod were not associated with clinically relevant QT\/QTc effects in healthy adults and only had a mild, transient, and asymptomatic impact on heart rate.<\/jats:p>","DOI":"10.1002\/cpdd.1388","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T07:44:47Z","timestamp":1709624687000},"page":"326-340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cardiovascular Evaluation of Etrasimod, a Selective Sphingosine 1\u2010phosphate Receptor Modulator, in Healthy Adults: Results of a Randomized, Thorough QT\/QTc Study"],"prefix":"10.1002","volume":"13","author":[{"given":"Borje","family":"Darpo","sequence":"first","affiliation":[{"name":"ERT Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalvin","family":"Connor","sequence":"additional","affiliation":[{"name":"ERT Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Cabell","sequence":"additional","affiliation":[{"name":"Arena Pharmaceuticals, San Diego, CA, USA, a wholly\u2010owned subsidiary of Pfizer Inc New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Grundy","sequence":"additional","affiliation":[{"name":"Arena Pharmaceuticals, San Diego, CA, USA, a wholly\u2010owned subsidiary of Pfizer Inc New York NY 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MorganM ChristopherR et\u00a0al.Safety pharmacokinetics and pharmacodynamics of etrasimod (APD334) an oral selective S1P receptor modulator after single dose escalation in healthy volunteers.Poster presented at: Advances in Inflammatory Bowel Diseases Conference; December 8\u201010 2016;Orlando FL.","DOI":"10.1093\/ecco-jcc\/jjx002.494"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx002.114"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx180.700"},{"key":"e_1_2_10_22_1","unstructured":"SchreiberS MorganM ChristopherR et\u00a0al.Etrasimod (APD334) a potent selective oral S1P receptor modulator with preclinical autoimmune disease\u2010modifying activity exhibits favorable PK\/PD properties in healthy volunteers.Poster presented at: Advances in Inflammatory Bowel Diseases Conference; December 8\u201010 2016;Orlando 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