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

A Two-part, Randomized, Placebo Controlled, Double Blind, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis (PBC)

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.

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.