Linerixibat Long-term Safety, and Tolerability Study

JRCT ID: jRCT2080225120

Registered date:10/03/2020

Basic Information

• Recruitment status: recruiting
• Health condition(s) or Problem(s) studied: Primary Biliary Cholangitis (PBC)
• Date of first enrollment: 14/04/2020
• Target sample size: 305
• Countries of recruitment: Argentina,Brazil,Canada,China,France,Germany,Italy,Mexico,Poland,Russian Federation,Spain,United Kingdom,United States
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc :
INN of investigational material : Linerixibat
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material :

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material :

Outcome(s)

Primary Outcome

Safety
-Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs) [ Time Frame: Up to 66 months ]
-Number of participants with Severe AEs [ Time Frame: Up to 66 months ]

Secondary Outcome

Change in domain scores of the PBC-40 over time [ Time Frame: Baseline and up to 65 months ]
Change in health-related quality of life (QoL) by the Euro Quality-5 dimension-3 level (EQ-5D-3L) scores over time (Group 1 only) [ Time Frame: Baseline and up to 65 months ]
Change in self-rated health by EQ VAS scores over time (Group 1 only) [ Time Frame: Baseline and up to 65 months ]
Change in the Beck Depression Inventory (BDI-II) scores over time [ Time Frame: Baseline and up to 65 months ]
Number of participants with clinically significant changes in hematology, biochemistry (including lipid and liver parameters), and coagulation parameters [ Time Frame: Baseline and up to 65 months ]
Percentage of responders at Week 24 and Week 52 of continuous treatment (Group 2 only) [ Time Frame: Week 24 and Week 52 of continuous treatment ]
Percentage of participants with maintenance of efficacy at Week 52 of continuous treatment in those that were responders at Week 24 of continuous treatment (Group 2 only) [ Time Frame: Week 52 of continuous treatment ]
Change from Baseline Monthly Sleep Score (MSS) (Group 2 only) [ Time Frame: Baseline and up to Week 52 of continuous treatment ]
Change from Baseline in Monthly Fatigue Score (MFS)(Group 2 only) [ Time Frame: Baseline and up to Week 52 of continuous treatment ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: GlaxoSmithKline K.K.
• Secondary ID(s): NCT04167358,JapicCTI-205215