{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:42:13Z","timestamp":1789810933551,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ozanimod is a novel, selective, oral sphingosine\u20101\u2010phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double\u2010blind, placebo\u2010controlled, positive\u2010controlled, parallel\u2010group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2\u00a0mg over 14\u00a0days) or placebo (for 14\u00a0days). A single dose of moxifloxacin 400\u00a0mg or placebo was administered on days 2 and 17. The primary end point was the time\u2010matched, placebo\u2010corrected, baseline\u2010adjusted mean QTcF (\u0394\u0394QTcF). A total of 113\/124 (91.1%) subjects completed the study. The upper limits of the 2\u2010sided 90% confidence intervals for \u0394\u0394QTcF for both ozanimod 1 and 2\u00a0mg were below the 10\u2010millisecond regulatory threshold. No QTcF &gt;480\u00a0milliseconds or postdose change in QTcF of &gt;60\u00a0milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and \u0394\u0394QTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile.<\/jats:p>","DOI":"10.1002\/cpdd.383","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T16:52:40Z","timestamp":1502124760000},"page":"263-276","source":"Crossref","is-referenced-by-count":63,"title":["Cardiac Safety of Ozanimod, a Novel Sphingosine\u20101\u2010Phosphate Receptor Modulator: Results of a Thorough QT\/QTc Study"],"prefix":"10.1002","volume":"7","author":[{"given":"Jonathan Q.","family":"Tran","sequence":"first","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Hartung","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan D.","family":"Olson","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boaz","family":"Mendzelevski","sequence":"additional","affiliation":[{"name":"Bioclinica Inc  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg A.","family":"Timony","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus F.","family":"Boehm","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Peach","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Gujrathi","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Frohna","sequence":"additional","affiliation":[{"name":"Receptos a wholly owned subsidiary of Celgene Corporation  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13476"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00018-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513248"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200176200"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00451.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22426"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21227"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1014-4"},{"key":"e_1_2_10_10_1","first-page":"1","article-title":"The organization of the sphingosine 1\u2010phosphate signaling system","volume":"378","author":"Rosen H","year":"2014","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907839"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909494"},{"key":"e_1_2_10_13_1","unstructured":"U.S. Food and Drug Administration. 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