{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:52:32Z","timestamp":1790661152835,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>\n                    Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium\u2010dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for \u22656\u00a0months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20\u00a0mg\/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO\u2122) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13\/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n\u00a0=\u00a024). Mean ItchRO\u2122 weekly sum scores decreased from baseline to week 13\/ET with maralixibat (\u201326.5; 95% confidence interval [CI], \u201331.8, \u201321.2) and placebo (\u201323.4; 95% CI, \u201330.3, \u201316.4). The difference between groups was not significant (\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    =\u00a00.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%).\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1305","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T11:24:52Z","timestamp":1549020292000},"page":"365-381","source":"Crossref","is-referenced-by-count":96,"title":["A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis"],"prefix":"10.1097","volume":"3","author":[{"given":"Marlyn J.","family":"Mayo","sequence":"first","affiliation":[{"name":"Digestive and Liver Diseases,University of Texas Southwestern Medical Center,Dallas,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Pockros","sequence":"additional","affiliation":[{"name":"Scripps Clinic and Scripps Translational Science Institute,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-6811","authenticated-orcid":false,"given":"Christopher L.","family":"Bowlus","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,University of California Davis School of Medicine,Sacramento,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Levy","sequence":"additional","affiliation":[{"name":"Division of Hepatology,University of Miami Miller School of Medicine,Miami,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Patanwala","sequence":"additional","affiliation":[{"name":"Royal Liverpool University Hospital and University of Liverpool,Liverpool,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Bacon","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Saint Louis University School of Medicine,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velimir","family":"Luketic","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Virginia Commonwealth University School of Medicine,Richmond,VA"},{"name":"McGuire Research Institute, McGuire VA Medical Center,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Vuppalanchi","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Medendorp","sequence":"additional","affiliation":[{"name":"Premier Research,Research Triangle Park,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Dorenbaum","sequence":"additional","affiliation":[{"name":"Stanford University,Palo Alto,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Amplyx Pharmaceuticals,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Novak","sequence":"additional","affiliation":[{"name":"Lumena Pharmaceuticals,San Diego,CA (one of the Shire group of 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