Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis

Abstract

Aim: To compare patient characteristics and outcomes between the overall and Japanese populations of GLIMMER.

Methods: GLIMMER was a multicenter, double-blind, randomized, placebo-controlled, Phase IIb study evaluating linerixibat for the treatment of pruritus in patients with primary biliary cholangitis.

Results: In total, 147 patients were randomized in the GLIMMER overall population with 38 patients comprising the Japanese population. Demographics and baseline clinical characteristics were similar across treatment groups and between both populations. A reduction in mean worst daily itch score from baseline to week 16 (primary endpoint) was seen in all groups, with the largest reduction observed with linerixibat 40 mg twice daily (BID; -2.92 [95% confidence interval: -5.07, -0.76] and -2.86 [95% confidence interval: -3.76, -1.95] for Japanese and overall populations, respectively). The highest proportion of responders was generally in the 40 mg BID group in both populations regardless of the responder definition applied. Improvements in health-related quality of life were generally consistent in both populations. In the Japanese and overall populations, on-treatment drug-related adverse events were reported in 25% and 19% of patients in the placebo group and 0%-86% and 31%-78% of patients in the linerixibat groups, respectively. Consistent with the mechanism of action, the most common events were gastrointestinal in nature. The effects of linerixibat on pharmacodynamic biomarkers favored BID dosing.

Conclusions: Therapeutic responses and safety of linerixibat were consistent between the Japanese and overall populations of GLIMMER. Linerixibat may provide an effective treatment option for cholestatic pruritus in patients with primary biliary cholangitis.

Clinical trial registration: NCT02966834.

Keywords: bile acid transporter; bile acids; cholestasis; health-related quality of life; primary biliary cholangitis; pruritus.