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

NCT05393076 | Completed Phase 1 FDA Drug

• 1 other identifier: 214899
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Pruritus

Keywords

Linerixibat; Pruritus; GSK2330672; Pharmacokinetics; Primary biliary cholangitis; Hepatic impairment; Liver Cirrhosis

Outcome Measures

Primary Outcomes (2)

• Plasma area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] following a single dose of linerixibat

  Up to Day 3

• Maximum observed concentration (Cmax) following a single dose of linerixibat

  Up to Day 3

Secondary Outcomes (9)

• Number of participants with adverse events (AEs) and serious adverse events (SAEs)

  Up to Day 14

• Number of participants with clinically significant change from baseline in electrocardiogram (ECG)

  Baseline (Day -1) and up to Day 3

• Number of participants with clinically significant change from baseline in vital signs

  Baseline (Day -1) and up to Day 3

• Number of participants with clinically significant change from baseline in clinical laboratory tests

  Baseline (Day -1) and up to Day 3

• Plasma area under the concentration-time curve from time zero (pre-dose) to 24 hours [AUC (0- 24)] following a single dose of linerixibat

  Up to Day 3

Study Arms (2)

Cohort 1 (Moderate hepatic impairment participants)

EXPERIMENTAL

Eligible participants to receive single dose of linerixibat.

Drug: Linerixibat

Cohort 2 (Matched healthy control participants)

EXPERIMENTAL

Eligible participants to receive single dose of linerixibat

Drug: Linerixibat

Interventions

Linerixibat DRUG

Linerixibat dose and administration as per study intervention.

Cohort 1 (Moderate hepatic impairment participants); Cohort 2 (Matched healthy control participants)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Orlando, Florida, 32809, United States

Location

GSK Investigational Site

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Conditions

Pruritus; Liver Cirrhosis, Biliary; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Fibrosis; Pathologic Processes

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-label study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This phase 1 study is an open-label, non-randomized, single-dose linerixibat study with 2 cohorts (moderate hepatic impairment and matched healthy control participants).

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: May 26, 2022
• Study Start: July 19, 2022
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: January 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (2)