Linerixibat Long-term Safety, and Tolerability Study

Phase 3Active Not RecruitingNCT04167358

GlaxoSmithKline245 enrolled

Overview

This is an open-label, non-comparator, global, multi-center, long-term safety study for evaluating safety and tolerability of linerixibat in participants with cholestatic pruritus in primary biliary cholangitis (PBC) who participated in a prior clinical trial with linerixibat (BAT117123 \[NCT01899703\], 201000 GLIMMER \[NCT02966834\] (group 1) or 212620 GLISTEN \[NCT00210418\]) (group 2). All participants will receive open-label linerixibat for the duration of the study. The study duration is expected to last until the study's end or until linerixibat can be lawfully made available to participants. However, the total duration of study participation will vary by participant depending upon the time of entry relative to study end in their respective country.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

245

Conditions

Cholestasis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female participants must be 18 to 80 years of age inclusive, at the time of signing the informed consent in the participant's parent trial BAT117213, GLIMMER or GLISTEN. * Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical trial (BAT117213, GLIMMER or GLISTEN). * Participants must have completed the main treatment period in a prior eligible linerixibat clinical trial (BAT117213, GLIMMER or GLISTEN). * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a) is a woman of non-childbearing potential (WONCBP) or b) is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method. * Capable of giving signed informed consent. Exclusion Criteria: * Screening total bilirubin \>2x upper limit of normal (ULN). * Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>6x ULN. * Screening estimated glomerular filtration rate (eGFR) \<30 milliliters per minute per 1.73 square meter (mL/min/1.73m\^2) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. * Presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites). * Presence of actively replicating viral hepatitis B or C (Viral Hepatitis B \[HBV\], viral Hepatitis C \[HCV\]) infection), primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer. * Current clinically significant diarrhea in the Investigator's medical opinion. * Current symptomatic cholelithiasis or cholecystitis. * Current diagnosis or previous diagnosis of colorectal cancer. * Any current malignancies (including hematologic and solid malignancies). * History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years. * Use of Obeticholic acid: within 8 weeks prior to the date of the screening visit and may not restart until after the end of the study or early study withdrawal. * Administration of any other ileal bile acid transporter (IBAT) inhibitor in the 1 month prior to screening until after the end of the study or early study withdrawal. * QT interval corrected (QTc) \>480 millisecond (msec) at screening (12-lead ECG) * Participants with moderate (or greater) alcohol consumption defined as more than one standard drink per day for women and two drinks per day for men.

Locations (95)

GSK Investigational Site

Davis, California, United States

GSK Investigational Site

West Hollywood, California, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

New York, New York, United States

Outcomes

Primary Outcomes

Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs)

AEs and SAEs will be collected.

Time frame: Up to 66 months

Number of participants with Severe AEs

AEs and SAEs will be collected.

Time frame: Up to 66 months

Secondary Outcomes

Change in domain scores of the PBC-40 over time

The PBC-40 is a participant-derived, disease specific health-related quality of life (QoL) measure with data to support its validity in PBC. The PBC-40 measure is comprised of 40 questions, each scored on a scale of 1 to 5 (where 1 = least impact, 5 = greatest impact) grouped into six domains (symptoms, itch, fatigue, cognition, social, and emotional).