Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN)

NCT ID: NCT04950127

Last Updated: 2025-07-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

238 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-27

Study Completion Date

2024-12-20

Brief Summary

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This is a 2-part study in PBC participants with cholestatic pruritus and will evaluate the efficacy, safety and impact on health-related quality of life of linerixibat compared with placebo.

Detailed Description

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Conditions

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Pruritus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomized to receive linerixibat and/or placebo during the study.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Participants and investigator will be blinded to the study treatment.

Study Groups

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Part A: Linerixibat 40 milligrams (mg)

Participants were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) in Part A (up to Week 24).

Group Type EXPERIMENTAL

Linerixibat

Intervention Type DRUG

Participants will receive linerixibat.

Part A: Placebo

Participants were randomized to receive Placebo orally twice a day (BID) in Part A (up to Week 24).

Group Type EXPERIMENTAL

Linerixibat

Intervention Type DRUG

Participants will receive linerixibat.

Placebo

Intervention Type DRUG

Participants will receive placebo.

Part B: Placebo in Part A and Part B

Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, continued to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive placebo.

Part B: Placebo in Part A and Linerixibat 40 mg in Part B

Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, switched to receive linerixibat 40 mg tablet orally twice a day (BID) (from Week 24 to Week 32) in Part B.

Group Type EXPERIMENTAL

Linerixibat

Intervention Type DRUG

Participants will receive linerixibat.

Placebo

Intervention Type DRUG

Participants will receive placebo.

Part B: Linerixibat 40 mg in Part A and Placebo in Part B

Participants who were randomized to receive linerixibat 40 mg tablet orally BID (up to Week 24) in Part A, switched to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.

Group Type EXPERIMENTAL

Linerixibat

Intervention Type DRUG

Participants will receive linerixibat.

Placebo

Intervention Type DRUG

Participants will receive placebo.

Part B: Linerixibat 40 mg in Part A and Part B

Participants who were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) (up to Week 24) in Part A, continued to receive linerixibat 40 mg twice a day (BID) (from Week 24 to Week 32) in Part B.

Group Type EXPERIMENTAL

Linerixibat

Intervention Type DRUG

Participants will receive linerixibat.

Interventions

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Linerixibat

Participants will receive linerixibat.

Intervention Type DRUG

Placebo

Participants will receive placebo.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.
* Participants who have documented PBC.
* Participants who have moderate to severe itch.

Exclusion Criteria

* Total bilirubin \>2.0 times Upper Limit of Normal (ULN) using the average of two Baseline measures.
* Screening Alanine Aminotransferase (ALT) \> 6 times ULN in a single Baseline measure or ALT \> 5 times ULN using the average of two Baseline measures.
* Screening estimated glomerular filtration rate (eGFR) \<30 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2).
* History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
* Presence of HBsAg positive hepatitis B or hepatitis C (HCV) (anti-HCV and Ribonucleic acid \[RNA\] detected) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
* Current clinically significant diarrhea or active inflammatory ileal disease according to Investigator´s clinical judgment.
* Current symptomatic cholelithiasis or cholecystitis.
* Current diagnosis of primary skin disorders with itch as a characteristic feature (e.g., atopic dermatitis, psoriasis).
* Primary sleep disorders such as but are not limited to sleep apnea, narcolepsy, hypersomnia.
* Initiation, discontinuation or change in dose of ursodeoxycholic acid (UDCA), bezafibrate or fenofibrate in the 8 weeks prior to Screening.
* Use of obeticholic acid: within 8 weeks prior to Screening. (Participants may not initiate or restart during the study).
* Initiation, discontinuation, or change in dose of any of the following in the 8 weeks prior to Screening: bile acid binding resins, rifampicin, naltrexone, naloxone, nalfurafine, pregabalin, gabapentin, sertraline or other selective serotonin reuptake inhibitor (SSRIs), antihistamines used for the treatment of itching.
* Administration of any other human ileal bile acid transporter (IBAT) inhibitor in the 12 weeks prior to screening.
* Any planned procedures intended to treat cholestatic pruritus such as nasobiliary drainage or ultraviolet light therapy from Screening and throughout the study.
* History of sensitivity or intolerance to the study treatment.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Davis, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Colorado Springs, Colorado, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Detroit, Michigan, United States

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Jackson, Mississippi, United States

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Omaha, Nebraska, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Morrisville, North Carolina, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Buenos Aires, , Argentina

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Capital Federal, , Argentina

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Ciudad AutOnoma de Buenos Aire, , Argentina

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Ciudad Autonoma de Bueno, , Argentina

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Rosario, , Argentina

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San Nicolás, , Argentina

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Santa Fe, , Argentina

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Ghent, , Belgium

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Porto Alegre, Rio Grande do Sul, Brazil

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Botucatu, , Brazil

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Brasília, , Brazil

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Salvador, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Edmonton, Alberta, Canada

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Toronto, Ontario, Canada

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Chongqing, , China

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Guangzhou, , China

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Nanchang, , China

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Nanjing, , China

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Shanghai, , China

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Tianjin, , China

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Zhanjiang, , China

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Ostrava, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Créteil, , France

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Grenoble, , France

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Lille, , France

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Paris, , France

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Erlangen, , Germany

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Essen, , Germany

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Münster, , Germany

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Athens, , Greece

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Beersheba, , Israel

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Haifa, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Nahariya, , Israel

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Rehovot, , Israel

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Milan, , Italy

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Modena, , Italy

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Monza, , Italy

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Napoli, , Italy

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Negrar Verona, , Italy

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Palermo, , Italy

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Roma, , Italy

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Rozzano MI, , Italy

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Ehime, , Japan

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Fukui, , Japan

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Hiroshima, , Japan

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Hiroshima, , Japan

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Hokkaido, , Japan

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Ibaraki, , Japan

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Kagawa, , Japan

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Kanagawa, , Japan

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Nagano, , Japan

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Nagasaki, , Japan

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Nara, , Japan

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Shizuoka, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Mexico City, , Mexico

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Mexico City, , Mexico

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Monterrey, , Mexico

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Częstochowa, , Poland

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Katowice, , Poland

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Mysłowice, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Kemerovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Samara, , Russia

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Basingstoke, , United Kingdom

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Cambridge, , United Kingdom

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Durham, , United Kingdom

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Hull, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Plymouth, , United Kingdom

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Reading Berkshire, , United Kingdom

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Southampton, , United Kingdom

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Surrey, , United Kingdom

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Countries

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United States Argentina Belgium Brazil Bulgaria Canada China Czechia France Germany Greece Israel Italy Japan Mexico Poland Russia Spain United Kingdom

References

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Carreno F, Karatza E, Mehta R, Collins J, Austin D, Swift B. Population Dose-Response-Time Analysis of Itch Reduction and Patient-Reported Tolerability Supports Phase III Dose Selection for Linerixibat. Clin Pharmacol Ther. 2024 Feb;115(2):288-298. doi: 10.1002/cpt.3103. Epub 2023 Dec 3.

Reference Type DERIVED
PMID: 37953500 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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212620

Identifier Type: -

Identifier Source: org_study_id

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