{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:29:19Z","timestamp":1770460159036,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015311","name":"Novartis Institutes for Biomedical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015311","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In primary bile acid diarrhoea, feedback by farnesoid X receptor (FXR) and fibroblast growth hormone 19 (FGF19) on hepatic bile acid production is impaired.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the safety, mechanisms and efficacy of negative feedback by FXR activation with tropifexor, a non\u2010bile acid FXR agonist, in patients with primary bile acid diarrhoea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this double\u2010blind, multicentre, randomised, cross\u2010over study, patients received tropifexor 60\u00a0\u00b5g or placebo once daily for 14\u00a0days in each of two treatment periods. Primary objectives included tropifexor safety and tolerability, and on stool frequency and form. Other assessments included pharmacokinetic and pharmacodynamic measures, biochemical markers and gastrointestinal transit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty patients (tropifexor 60\u00a0\u00b5g\/placebo [N\u00a0=\u00a010]; placebo\/tropifexor 60\u00a0\u00b5g [N\u00a0=\u00a010]) were enrolled. Adverse event rates were lower with tropifexor vs placebo (52.9% vs 73.7%). No patient had pruritus during tropifexor intake. There were no significant differences in stool frequency, stool form or loperamide use between treatments. Tropifexor increased FGF19 and decreased 7\u03b1\u2010hydroxy\u20104\u2010cholesten\u20103\u2010one (C4) levels for up to 8\u00a0h. Plasma tropifexor concentrations peaked at 5\u00a0hours post\u2010dose on days 1 and 12. At day 12, tropifexor caused reduction in peak total bile acid concentration (33%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.032) and exposure (36%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.005). Moreover, tropifexor showed a significant increase in ascending colon half\u2010emptying time (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.036).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tropifexor 60\u00a0\u00b5g once daily had acceptable safety and tolerability. Changes in FGF19 and C4 showed effective target engagement; however, higher doses may be required to observe stool frequency changes. Slowing of ascending colon emptying suggests therapeutic potential of tropifexor in patients with primary bile acid diarrhoea.<\/jats:p><jats:p>ClinicalTrials.gov number: NCT02713243.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15967","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T16:14:59Z","timestamp":1595520899000},"page":"808-820","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Randomised clinical trial: significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-7514","authenticated-orcid":false,"given":"Michael","family":"Camilleri","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Linker","family":"Nord","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duane","family":"Burton","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibironke","family":"Oduyebo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceutical Corporation East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koeun","family":"Im","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prafulla","family":"Bhad","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael K.","family":"Badman","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Sanders","sequence":"additional","affiliation":[{"name":"The Academic Unit of Gastroenterology Royal Hallamshire Hospital Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-5835","authenticated-orcid":false,"given":"Julian R. 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