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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04167358




Registration number
NCT04167358
Ethics application status
Date submitted
15/11/2019
Date registered
18/11/2019
Date last updated
7/11/2023

Titles & IDs
Public title
Linerixibat Long-term Safety, and Tolerability Study
Scientific title
Long-term Safety and Tolerability Study of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis
Secondary ID [1] 0 0
2019-003158-10
Secondary ID [2] 0 0
212358
Universal Trial Number (UTN)
Trial acronym
LLSAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cholestasis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Linerixibat

Experimental: Participants receiving linerixibat - 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: Drugs: Linerixibat
All participants will receive linerixibat.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs)
Timepoint [1] 0 0
Up to 66 months
Primary outcome [2] 0 0
Number of participants with Severe AEs
Timepoint [2] 0 0
Up to 66 months
Secondary outcome [1] 0 0
Change in domain scores of the PBC-40 over time
Timepoint [1] 0 0
Baseline and up to 65 months
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Baseline and up to 65 months
Secondary outcome [3] 0 0
Change in self-rated health by EQ VAS scores over time (Group 1 only)
Timepoint [3] 0 0
Baseline and up to 65 months
Secondary outcome [4] 0 0
Change in the Beck Depression Inventory (BDI-II) scores over time
Timepoint [4] 0 0
Baseline and up to 65 months
Secondary outcome [5] 0 0
Number of participants with clinically significant changes in hematology, biochemistry (including lipid and liver parameters), and coagulation parameters
Timepoint [5] 0 0
Baseline and up to 65 months
Secondary outcome [6] 0 0
Percentage of responders at Week 24 and Week 52 of continuous treatment (Group 2 only)
Timepoint [6] 0 0
Week 24 and Week 52 of continuous treatment
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
Week 52 of continuous treatment
Secondary outcome [8] 0 0
Change from Baseline Monthly Sleep Score (MSS) (Group 2 only)
Timepoint [8] 0 0
Baseline and up to Week 52 of continuous treatment
Secondary outcome [9] 0 0
Change from Baseline in Monthly Fatigue Score (MFS)(Group 2 only)
Timepoint [9] 0 0
Baseline and up to Week 52 of continuous treatment

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/02/2027
Actual
Sample size
Target
305
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Colorado
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Florida
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Michigan
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Nebraska
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New York
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North Carolina
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Ohio
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Texas
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Washington
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Argentina
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Buenos Aires
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Santa Fe
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Bahia
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Plovdiv
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Sofia
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Ontario
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Canada
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Quebec
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China
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Guangdong
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China
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Jiangsu
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China
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Jiangxi
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China
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Jilin
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China
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Sichuan
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China
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Beijing
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China
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Shanghai
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China
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Tianjin
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China
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Xi'an
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China
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Zhengzhou
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Czechia
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Ostrava
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Czechia
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Plzen
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Czechia
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Praha 4
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France
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Lille cedex
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Bayern
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Germany
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Nordrhein-Westfalen
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Greece
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Athens
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Israel
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Beer Sheva
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Israel
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Haifa
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Israel
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Holon
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Jerusalem
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Israel
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Nahariya
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Ramat Gan
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Rehovot
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Emilia-Romagna
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Lazio
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Gunma
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Hokkaido
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Nagano
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Nagasaki
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Nara
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Osaka
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Japan
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Shizuoka
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Japan
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Tokyo
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Mexico
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Ciudad De Mexico
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Mexico
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Nuevo León
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Poland
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Czestochowa
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Poland
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Katowice
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Myslowice
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Warszawa
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Poland
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Wroclaw
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Russian Federation
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Kemerovo
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Russian Federation
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Moscow
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Russian Federation
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Samara
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Spain
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Valencia
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Switzerland
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Lugano
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United Kingdom
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Surrey
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Basingstoke
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Cambridge
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Glasgow
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Hull
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Liverpool
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London
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Newcastle Upon Tyne
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Nottingham
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United Kingdom
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Plymouth
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United Kingdom
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Reading
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United Kingdom
State/province [88] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04167358
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04167358