inerixibat Long-term Safety and Tolerability Study (LLSAT)

Phase 1

Conditions: MedDRA version: 21.0Level: PTClassification code 10080429Term: Primary biliary cholangitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Moderate to Severe Pruritus (itching) caused by primary biliary cholangitis (PBC)
MedDRA version: 21.1Level: PTClassification code 10064190Term: Cholestatic pruritusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2019-003158-10-PL

Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 75

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 trial
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 trial(BAT117213, GLIMMER or GLISTEN)
3. Participants must have completed the main treatment period(s) in a
prior eligible linerixibat clinical trial (BAT117213, GLIMMER or GLISTEN)
Contraception requirements
4. Contraceptive use by women should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies. Contraception by male participants or
male partners of female participants is not required in this protocol
-A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
o Is not a woman of childbearing potential (WOCBP)
OR
o Is a WOCBP and using a contraceptive method that is highly effective
(with a failure rate of <1% per year), with low user dependency, as
described in Appendix 4 of Protocol, during the intervention period and
for at least 4 weeks, after the last dose of study intervention. The
investigator should evaluate the effectiveness of the contraceptive
method in relationship to the first dose of study intervention
-A WOCBP must have a negative highly sensitive pregnancy test (urine
or serum as required by local regulations) within 24 hours before the
first dose of study intervention
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 Appendix 4: Contraceptive Guidance and
Collection of Pregnancy Information of Protocol
-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
-Informed Consent
5. Capable of giving signed informed consent as described in Appendix 1
of protocol, 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 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Participants are excluded from the study if any of the following criteria
apply:
Medical Conditions
1. Screening total bilirubin >2x ULN.
Note: 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. History or presence of hepatic decompensation (e.g., variceal
bleeding, encephalopathy or ascites)
5. 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
6. Current clinically significant diarrhea in the Investigator's medical
opinion
7. Current symptomatic cholelithiasis or cholecystitis. Participants with
history of cholecystectomy =3 months before screening may be eligible
for enrollment
8. Current diagnosis or previous diagnosis of colorectal cancer
9. Any current malignancies (including hematologic and solid
malignancies).
10. History of bariatric surgery with ileal bypass at any time, or any
bariatric surgery performed in the past 3 years.
11. 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
12. 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
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]
13. Administration of any other IBAT inhibitor in the 1 month prior to
screening [Rationale: Effects of another IBAT inhibitor may confound
interpretation of the linerixibat safety and tolerability profile]
Prior/Concurrent Clinical Study Experience
14. 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
15. 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 individual participants throughout study
participation. The specific QT correction formula used must be specified
in the eCRF
The QT interval will be assessed at screening and at each long visit
(yearly) by 12-Lead ECG. QTc stopping criteria are established for this
study and are detailed in [Section 7.1.3] of Protocol
Other Exclusions
16. History of regular alcohol consumption within 6 months of the study
defined as an average weekly intake of >14 units for males or >7 units
for females. One unit is equivalent to

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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