Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants With Primary Biliary Cholangitis

Summary

This study is being conducted to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus (itch) in participants with primary biliary cholangitis (PBC). Participants will receive either placebo or one of the 4 dose regimens of GSK2330672 (20 milligram \[mg\], 90 mg or 180 mg taken once daily or 90 mg twice daily). Participants on GSK2330672 will also receive placebo tablets to maintain blinding. The study has a prospectively defined adaptive design that will utilize interim data to further inform and potentially optimize the doses under investigation. Hence, additional dose regimen may be added during study. The total duration of a participant in the study will be up to 45 days of screening and 24 weeks of study including follow-up.

Timeline

Start

2017-01-11

Primary completion

2020-04-15

Completion

2020-04-15

Outcome

Missed primary endpoint

paper Linerixibat effect on itch was not significantly different versus placebo in the primary intent-to-treat analysis PMID 36343847 ↗

Publications

• Karatza E, Swift B, Carreno F, Mukherjee S, Casillas L, Lennie J, Fettiplace J, McLaughlin MM, Kremer AE. Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat. Liver Int. 2024 Sep;44(9):2293-2302. doi: 10.1111/liv.15982. Epub 2024 May 23.
• Carreno F, Karatza E, Mehta R, Collins J, Austin D, Swift B. Population Dose-Response-Time Analysis of Itch Reduction and Patient-Reported Tolerability Supports Phase III Dose Selection for Linerixibat. Clin Pharmacol Ther. 2024 Feb;115(2):288-298. doi: 10.1002/cpt.3103. Epub 2023 Dec 3.
• Tanaka A, Atsukawa M, Tsuji K, Notsumata K, Suyama A, Ito H, Das S, von Maltzahn R, McLaughlin MM. Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis. Hepatol Res. 2023 Jul;53(7):629-640. doi: 10.1111/hepr.13895. Epub 2023 Mar 13.
• Levy C, Kendrick S, Bowlus CL, Tanaka A, Jones D, Kremer AE, Mayo MJ, Haque N, von Maltzahn R, Allinder M, Swift B, McLaughlin MM, Hirschfield GM; GLIMMER Study Group. GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1902-1912.e13. doi: 10.1016/j.cgh.2022.10.032. Epub 2022 Nov 4.

Drugs

Indications