Linerixibat Long-term Safety, and Tolerability Study (LLSAT)

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 3

Conditions: Cholestasis

Treatments: Drug: Linerixibat

Study type: Interventional

Funder types: Industry

Identifiers

NCT04167358

2019-003158-10 (EudraCT Number)

212358

Details and patient eligibility

About

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.

Enrollment: 251 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

251 participants in 1 patient group

Participants receiving linerixibat

Experimental group

Description:

Participants who previously participated in the Phase 2 studies (BAT117213 and 201000 GLIMMER \[Group 1\]) and Phase 3 study (212620 GLISTEN \[Group 2\]), will receive linerixibat.

Treatment:

Drug: Linerixibat