A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Repeat Doses of GSK2330672 Administration in Subjects With Primary Biliary Cirrhosis (PBC) and Symptoms of Pruritus

Summary

This will be a randomized, double-blind, placebo-controlled study to assess safety and tolerability of GSK2330672 administration in subjects with primary biliary cirrhosis (PBC) and symptoms of pruritus. It is a double-blind, crossover study with subjects receiving placebo or GSK23306772 in random order during two 14-day treatment periods. Additionally, the study will determine GSK2330672 exposure and interactions with ursodeoxycholic acid (UDCA). The total duration of subject participation will be 14 weeks for screening (45 days) and the treatment period. Subjects who are eligible for enrolment will participate in a 2-week placebo run-in period. Subjects will be randomized in a crossover fashion (Sequence 1 / Sequence 2) to receive placebo or GSK2330672 treatment during two consecutive 2-week study periods. Subjects will then participate in a 2-week placebo dosing follow-up period ending in final follow-up assessments. Study results will be utilized to form a benefit: risk profile for GSK2330672 in PBC that will determine plans for progression to exploratory efficacy trials

Timeline

Start

2014-03-10

Primary completion

2015-10-07

Completion

2015-10-07

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.
• Hegade VS, Kendrick SF, Dobbins RL, Miller SR, Thompson D, Richards D, Storey J, Dukes GE, Corrigan M, Oude Elferink RP, Beuers U, Hirschfield GM, Jones DE. Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Lancet. 2017 Mar 18;389(10074):1114-1123. doi: 10.1016/S0140-6736(17)30319-7. Epub 2017 Feb 8.
• Hegade VS, Kendrick SF, Dobbins RL, Miller SR, Richards D, Storey J, Dukes G, Gilchrist K, Vallow S, Alexander GJ, Corrigan M, Hirschfield GM, Jones DE. BAT117213: Ileal bile acid transporter (IBAT) inhibition as a treatment for pruritus in primary biliary cirrhosis: study protocol for a randomised controlled trial. BMC Gastroenterol. 2016 Jul 19;16(1):71. doi: 10.1186/s12876-016-0481-9.

Drugs

Indications