A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis

作者：Marlyn J. Mayo, Paul J. Pockros, David E. Jones, Christopher L. Bowlus, Cynthia Levy, Imran Patanwala, Bruce R. Bacon, Velimir A. Luketic, Raj Vuppalanchi, SHARON VANDERBRUG MEDENDORP, Alejandro Dorenbaum, Ciara Kennedy, Patricia L. Novak, Joan Gu, George Apostol, Gideon Morris Hirschfield · 发表于：Hepatology Communications · 年份：2019 · DOI：10.1002/hep4.1305 · 被引用次数：97 · 研究领域：Liver Diseases and Immunity、Drug Transport and Resistance Mechanisms、Pediatric Hepatobiliary Diseases and Treatments

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‐dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) 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 = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (–26.5; 95% confidence interval [CI], –31.8, –21.2) and placebo (–23.4; 95% CI, –30.3, –16.4). The difference between groups was not significant ( P = 0.48). 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%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of...