{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T23:31:43Z","timestamp":1793921503067,"version":"4.8.0"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Aberrant farnesoid X receptor (FXR) signaling is implicated in cholestatic, inflammatory, and fibrotic liver diseases. In preclinical\/clinical studies, semisynthetic bile acid\u2010derived FXR agonists markedly improved hepatic function in various conditions. INT\u2010787, a novel hydrophilic semisynthetic bile acid FXR agonist, has demonstrated a reduction in inflammatory and fibrotic markers and regulation of bile acid\/lipid metabolism. This first\u2010in\u2010human, randomized, placebo\u2010controlled phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of INT\u2010787 and its equipotent metabolites in healthy volunteers by evaluating single ascending doses (SAD), multiple ascending doses (MAD), and food effect. Participants (<jats:italic>n<\/jats:italic>\u2009=\u2009130) across all study portions were similar in age, race, and body mass index. In the SAD and MAD portions, the maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and area under the curve (AUC) for total INT\u2010787 generally increased with dose. In the Food Effect portion, the mean <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of total INT\u2010787 was almost 2\u2010fold higher under fasted conditions compared with fed conditions; AUC<jats:sub>0\u2010inf<\/jats:sub> was unchanged. Steady state for total INT\u2010787 was reached by Day 7. In cohorts receiving \u2265\u200950\u2009mg doses, the half\u2010life of total INT\u2010787 ranged from 21 to 55\u2009h. INT\u2010787 metabolites exhibited increased concentrations after mealtimes despite morning dosing, consistent with endogenous bile acid behavior. Following single and multiple doses of INT\u2010787, decreases in C4 and increases in FGF\u201019 levels were observed. Single and multiple oral doses were generally well tolerated; 4 adverse events of mild, transient pruritus not requiring interventions were reported at higher doses. These results warrant further investigation of INT\u2010787 in patients with liver\u2010related disorders.<\/jats:p>","DOI":"10.1111\/cts.70229","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T22:29:21Z","timestamp":1746052161000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of <scp>INT<\/scp>\u2010787, a Novel Farnesoid X Receptor Agonist, in Healthy Volunteers: A Phase 1 Trial"],"prefix":"10.1111","volume":"18","author":[{"given":"Thomas","family":"Capozza","sequence":"first","affiliation":[{"name":"Intercept Pharmaceuticals, Inc  Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Burkey","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc  Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Van De Wetering","sequence":"additional","affiliation":[{"name":"ICON  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold","family":"Kerb","sequence":"additional","affiliation":[{"name":"ICON  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Callahan","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc  Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Kryzhanovskaya","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc  Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Erickson","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc  Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)00062\u20103"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1016836"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2014.12.011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00544"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2022.111678"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01126"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004166\u20108"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64551"},{"key":"e_1_2_10_10_1","unstructured":"L.Adorini K.Rigbolt K.Voldem\u2010Clausen M.Feigh S.Amuthakannan andM.Erickson \u201cThe Novel FXR Agonist INT\u2010787 Shows Higher Efficacy as Well as Greater Hepatic and Ileal Gene Modulation Than Obeticholic Acid in the Gubra\u2010Amln Mouse Model of Diet\u2010Induced and Biopsy\u2010Confirmed Nonalcoholic Steatohepatitis \u201d2022 Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; 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