Phase I Study of Linerixibat in Adults With Moderate Hepatic Impairment and Healthy Controls

• Status: Not yet recruiting
• Trial end date: 2022-10-06
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 1, open-label, single-dose study in adults with moderate hepatic impairment (defined as Child-Pugh B cirrhosis) and matched healthy control participants with normal hepatic function. All participants in both cohorts (moderate hepatic impairment and matched healthy controls) will receive a single dose of the study drug, linerixibat. The purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (PK) and safety of linerixibat.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

Inclusion Criteria:

All Participants:

• Age: 18 to 75 years of age (inclusive).

• Weight greater than (>) 45 kilograms (kg) and body mass index (BMI) 18.5 - 40 kg per square meter (kg/m^2) (inclusive).

• Male and female- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment.

• Participant capable of giving signed informed consent.

Participants with Moderate Hepatic Impairment (Cohort 1):

• Moderate hepatic impairment (of any etiology) and clinically stable for at least 1 month prior to screening.

• Child-Pugh score of 7-9.

• Previous confirmation of liver cirrhosis confirmed by either- Liver biopsy, Imaging technique, or Noninvasive liver assessment consistent with cirrhosis.

• Hepatic impairment needs to be chronic (>6 months), stable.

Matched Healthy Control Participants (Cohort 2):

• Participants will be matched by age plus or minus (±)10 years to a corresponding participant in the hepatic impairment group. Age should remain between 18 and 75 years of age (inclusive).

• Participants will be matched by total body weight ±15 percentage (%) to a corresponding participant in the hepatic impairment group.

• Participants will be matched by gender and race to a corresponding participant in the hepatic impairment group.

• Healthy participant as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and ECG.

Exclusion Criteria:

All Participants:

• Participants are excluded from the study if any of the following medical conditions apply:

• History of cholecystectomy, current symptomatic cholelithiasis or inflammatory gallbladder disease.

• Significant history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.

• Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history review), clinical laboratory tests, or 12-lead ECG.

• Current clinically significant diarrhea.

• History of gastrointestinal surgery with ileal resection or ileal bypass at any time.

• Any malignancy within the past 5 years except for basal cell or squamous cell carcinoma of the skin disease for 3 years.

• Participants with unstable cardiac function or participants with uncontrolled hypertension.

• Any current medical or psychiatric condition, clinical or laboratory abnormality, or examination finding which may affect study compliance or investigational procedures or possible consequences of the study.

• Administration of any other Ileal bile acid transport (IBAT) inhibitor (including linerixibat) in the 3 months prior to screening.

• For healthy participants, past or intended use of over the counter or prescription medication, including vitamins and dietary or herbal supplements) within 7 days prior to the first dose of study medication.

• Current enrolment in a clinical trial or recent participation in a clinical trial and has received an investigational product within the following time-period prior to study drug administration in the current study: 30 days.

• Positive pregnancy test at screening or at Day -1 in women of childbearing potential.

• Positive human immunodeficiency virus (HIV) antibody test.

• Healthy control participant has corrected interval using the Fridericia's QT correction formula (QTcF) >450 millisecond (msec); or participant with hepatic impairment has a baseline QTcF >480 msec on ECG.

• Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.

• Moderate (or greater) alcohol consumption defined as one standard drink per day for women and two drinks per day for men.

• History of regular use of tobacco or nicotine-containing products.

• Positive drug/alcohol screen at Screening or at Day -1.

• Where participation in the study would result in donation of blood or blood products more than 500 milliliter (mL) within a 56-day period.

• Unwillingness or inability to follow the procedures outlined in the protocol.

• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study.

Participants with Hepatic Impairment (Cohort 1):

• History of gastric or oesophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated medically or endoscopically.

• Grade 3 ascites (large ascites with marked abdominal distension) refractory to medical therapy.

• Refractory hepatic encephalopathy as judged by the investigator.

• Child-Pugh score of 10 or higher or Child-Pugh score of 6 or lower.

• Hepatopulmonary or hepatorenal syndrome and history of liver transplantation.

• Evidence of active infection, including spontaneous bacterial peritonitis.

• Confirmed hepatocellular carcinoma (HCC) or biliary cancer.

• Alanine amino transferase (ALT) value >3 x upper limit of normal (ULN).

• Platelet count less than (<) 50,000/microliter (μl).

Matched Healthy control participants (Cohort 2):

• Current or chronic history of liver disease or known hepatic or biliary abnormalities and/or confirmed hepatocellular carcinoma or biliary cancer.

• Screening ALT or aspartate aminotransferase (AST) above the upper limit of normal (ULN).

• Elevated bilirubin above the ULN unless this is due to underlying Gilbert's syndrome.

• Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.

• Positive hepatitis C antibody ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.