{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:23:34Z","timestamp":1790785414942,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cilofexor is a nonsteroidal farnesoid X receptor (FXR) agonist being evaluated for treatment of nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC). This work characterized the pharmacokinetics, pharmacodynamic, safety, and tolerability of cilofexor in healthy participants. Cilofexor single and multiple once\u2010daily doses (10 to 300\u2009mg fasting or fed and twice\u2010daily doses [15 and 50\u2009mg; fed]; tablet formulation) were evaluated. In each cohort, participants were randomized to active drug or placebo in a 4:1 ratio (planned\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a015\/cohort). Multiple dosing was for 14\u2009days. Pharmacokinetic and pharmacodynamic samples were collected and safety and tolerability were assessed. Overall, 120 participants were enrolled in the study and 118 participants received at least one dose of study drug. Cilofexor pharmacokinetics followed bi\u2010exponential disposition and its exposure increased in a less\u2010than\u2010dose\u2010proportional manner over the 10 to 300\u2009mg dose range, with no significant accumulation with repeated dosing. Moderate\u2010fat meal reduced cilofexor area under the plasma concentration versus time curve (AUC) by 21% to 45%. Cilofexor increased plasma levels of fibroblast growth factor19 (FGF19) and reduced the serum bile acid intermediate 7\u03b1\u2010hydroxy\u20104\u2010cholesten\u20103\u2010one (C4) and bile acids in an exposure\u2010dependent manner. Cilofexor doses &gt;30\u2009mg appeared to achieve the plateau of intestinal FXR activation. Cilofexor was generally well tolerated; all treatment\u2010emergent adverse events (TEAEs) were mild or moderate in severity, with headache being the most frequently observed TEAE. The pharmacokinetics pharmacodynamic safety, and tolerability results from this study supported further evaluations, and informed dose selection, of cilofexor in phase II studies in patients with NASH and PSC.\n                  <\/jats:p>","DOI":"10.1111\/cts.13469","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T05:13:30Z","timestamp":1672118010000},"page":"536-547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal Farnesoid X\u00a0receptor agonist, in healthy volunteers"],"prefix":"10.1111","volume":"16","author":[{"given":"Islam R.","family":"Younis","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Kirby","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N.","family":"Billin","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deqing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Song","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4937-2775","authenticated-orcid":false,"given":"Ahmed A.","family":"Othman","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24491"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27368"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.07.056"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.710"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17158"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30509"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02484.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31622"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31205"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109609"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2021.1916465"},{"key":"e_1_2_12_13_1","unstructured":"United States Food and Drug Administration.Bioanalytical method validation: guidance for Industry;2018."},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2016-0689"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13469","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13469","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T18:14:58Z","timestamp":1692641698000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,15]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/cts.13469"],"URL":"https:\/\/doi.org\/10.1111\/cts.13469","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,15]]},"assertion":[{"value":"2022-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}