{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:00:19Z","timestamp":1787500819592,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"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":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The sphingosine\u20101\u2010phosphate 1 receptor (S1P\n                    <jats:sub>1R<\/jats:sub>\n                    ) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P\n                    <jats:sub>1R<\/jats:sub>\n                    and S1P\n                    <jats:sub>5R<\/jats:sub>\n                    receptors in clinical development for the treatment of chronic immune\u2010mediated, inflammatory diseases. This first\u2010in\u2010human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose\u2010escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg\/d, with no severe adverse events (AEs) and no dose\u2010limiting toxicities. The most common ozanimod\u2010related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady\u2010state volume of distribution (73\u2013101 L\/kg), moderate oral clearance (204\u2013227 L\/h), and an elimination half\u2010life of approximately 17 to 21 hours. Ozanimod produced a robust dose\u2010dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg\/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose\u2010dependent negative chronotropic effect was observed following the first dose, with the dose\u2010escalation regimen attenuating the first\u2010dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once\u2010daily regimens under clinical investigation.\n                  <\/jats:p>","DOI":"10.1002\/jcph.887","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T10:13:29Z","timestamp":1491905609000},"page":"988-996","source":"Crossref","is-referenced-by-count":107,"title":["Results From the First\u2010in\u2010Human Study With Ozanimod, a Novel, Selective Sphingosine\u20101\u2010Phosphate Receptor Modulator"],"prefix":"10.1002","volume":"57","author":[{"given":"Jonathan Q.","family":"Tran","sequence":"first","affiliation":[{"name":"Receptos, a wholly owned subsidiary of Celgene Corporation  San Diego CA 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 CA 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 CA 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 CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Rosen","sequence":"additional","affiliation":[{"name":"Scripps Research Institute  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Smith","sequence":"additional","affiliation":[{"name":"Receptos, a wholly owned subsidiary of Celgene Corporation  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Receptos, a wholly owned subsidiary of Celgene Corporation  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg A.","family":"Timony","sequence":"additional","affiliation":[{"name":"Receptos, a wholly owned subsidiary of Celgene Corporation  San Diego CA 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 CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Gujrathi","sequence":"additional","affiliation":[{"name":"Receptos, a wholly owned subsidiary of Celgene Corporation  San Diego CA 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 CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,11]]},"reference":[{"issue":"2","key":"e_1_2_8_2_1","first-page":"S21","article-title":"A review of current and emerging therapeutic strategies in multiple sclerosis","volume":"19","author":"Tullman MJ.","year":"2013","journal-title":"Am J Manag Care"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20797"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009283431307"},{"key":"e_1_2_8_5_1","first-page":"722","volume-title":"Cecil Textbook of Medicine","author":"Stenson W.","year":"2001"},{"key":"e_1_2_8_6_1","first-page":"1633","volume-title":"Harrison's Principles of Internal Medicine","author":"Glickman R.","year":"1998"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.06.081"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425240903134769"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/eci.10.46"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.35"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-015-0261-z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13476"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907839"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052643"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00041-7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006289853"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12336"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.01.021"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2003.02065.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00018-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513248"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio804"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12129"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.244"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004264165"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513500551"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.887","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T01:20:20Z","timestamp":1696382420000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,11]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1002\/jcph.887"],"URL":"https:\/\/doi.org\/10.1002\/jcph.887","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,11]]}}}