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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Pruritus

Treatments: Drug: Placebo; Drug: Linerixibat

Study type: Interventional

Funder types: Industry

Identifiers

NCT04950127

212620

Details and patient eligibility

About

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.

Enrollment: 238 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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238 participants in 6 patient groups, including a placebo group

Part A: Linerixibat 40 milligrams (mg)

Experimental group

Description:

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

Treatment:

Drug: Linerixibat

Part A: Placebo

Experimental group

Description:

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

Treatment:

Drug: Linerixibat

Drug: Placebo

Part B: Placebo in Part A and Part B

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: Linerixibat

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: Linerixibat

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: Linerixibat