inerixibat Long-term Safety and Tolerability Study (LLSAT)

Phase 1

Conditions: Moderate to Severe Pruritus (itching) caused by primary biliary cholangitis (PBC)
MedDRA version: 24.1Level: PTClassification code 10064190Term: Cholestatic pruritusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
MedDRA version: 21.0Level: PTClassification code 10080429Term: Primary biliary cholangitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2019-003158-10-BE

Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 295

Inclusion Criteria

Participants are eligible to be included in the study only if all the
following criteria apply:
Age
1. Male or female participants must be 18 to 80 years of age inclusive, at the time of signing the informed consent in the participant's parent study BAT117213, GLIMMER or GLISTEN
Note: if country/site age requirements for consent differ, the more stringent (e.g., higher age) restriction will be required for that country/site.
Type of Participant and Disease Characteristics
2.Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical study(BAT117213, GLIMMER or GLISTEN)
3.Participants must have completed the main treatment period(s) in a prior eligible linerixibat clinical study (BAT117213, GLIMMER or GLISTEN)
Contraception requirements
4.Contraceptive/Barrier Requirements (applicable for female participants only): A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP)
OR
o Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in Section 10.4 during the study intervention period (at a minimum until 4 weeks after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in
relationship to the first dose of study intervention, etc.).
-A WOCBP must have a negative highly sensitive urine pregnancy test (or serum, as required by local regulations) within 7 days before the first dose of study intervention, see Section 10.4 Pregnancy Testing.
o If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
• Additional requirements for pregnancy testing during and after study intervention are listed in Section 8.2.5 Pregnancy Testing and Section 10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Note: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Full requirements for pregnancy testing during and after study intervention are located in Section 10.4 Appendix 4.
Informed Consent
5. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion Criteria

Participants are excluded from the study if any of the following criteria
apply:
Medical Conditions
1.Screening total bilirubin >2x ULN.
Notes: Total bilirubin >2x ULN but <3x ULN is acceptable if bilirubin is
fractionated and direct bilirubin is <35%
2.Screening ALT or aspartate aminotransferase (AST) >6x ULN
3.Screening estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
4. Group 2 Participants who meet increased liver chemistry monitoring criteria or any stopping criteria during LLSAT Screening period (GLISTEN Week 28 to Week 32 visit) or temporarily discontinue study treatment due to a drug-related adverse event during the LLSAT Screening period, which is ongoing before Baseline Visit.
Note: participants that meet increased liver chemistry monitoring criteria or stopping criteria at any timepoint during GLISTEN and restart of study intervention has not been approved by GSK are excluded
5. Presence of hepatic decompensation (e.g., variceal bleeding, encephalopathy or ascites)
6. Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection,primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer
7. Current clinically significant diarrhea in the Investigator's medical opinion
8. Current symptomatic cholelithiasis or cholecystitis. Participants with history of cholecystectomy =3 months before screening may be eligible for enrollment
9. Current diagnosis or previous diagnosis of colorectal cancer
10. Any current malignancies (including hematologic and solid malignancies).
11. History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years.
12. Any current medical condition (e.g. psychiatric disorder, senility or dementia), which may affect the participant's ability to comply with the protocol specified procedures
Prior/Concomitant Therapy
13. 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. [Rationale: The potential for a Drug-Drug Interaction (DDI) between obeticholic acid and linerixibat is under investigation. A DDI study assessing the concomitant use of OCA and 40 mg linerixibat twice daily is planned and depending on those results this
OCA exclusion may be removed]
14. Administration of any other IBAT inhibitor in the 1 month prior to screening until after End of Study or Early study withdrawal [Rationale: Effects of another IBAT inhibitor may confound interpretation of the linerixibat safety and tolerability profile]
Prior/Concurrent Clinical Study Experience
15. Current enrollment or participation in any other clinical study (except for GLISTEN) involving an investigational study treatment within 8 weeks prior to the screening visit
Note: For participants coming from the GLISTEN study there is no specified waiting period before enrollment into this safety study.
Diagnostic Assessments
16. QTc >480 msec at screening (12-lead ECG)
Notes: The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Frederica's formula (QTcF), and/or another method. It is either machine-read or manually over-read The specific formula used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study and maintained for individ