Food Effect Study of Linerixibat Tablets in Healthy Adult Participants

A Phase I, Randomized, Open-label, Single Dose, 2 Period, Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics of Linerixibat Tablets in Healthy Adult Participants

This study will evaluate the effect of food on the Pharmacokinetic (PK) and Pharmacodynamic (PD) parameters of linerixibat administered in fed and fasted states in heathy adult participants

Study Overview

• Status: Completed
• Conditions: Pruritus
• Intervention / Treatment: Drug: linerixibat

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0GG
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Overtly healthy male or female participants 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Participants' age greater than (>) 50 years old, must have had at least 3 weeks elapsed after the completion of an approved primary SARS-CoV-2 vaccination course.
• Body weight >50 kg and body mass index (BMI) within the range 18.5 - 32 kilogram per meter square (kg/m2) (inclusive).

• Female Participants:

  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
  • Is a woman of non-childbearing potential (WONCBP). OR
  • Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year).
• Capable of giving signed informed consent.

Exclusion Criteria:

• History of cholecystectomy.
• Current symptomatic cholelithiasis or inflammatory gall bladder disease.
• Significant history of or current disorders capable of significantly altering the absorption, metabolism, or elimination of drugs.
• 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 epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Administration of any other Ileal Bile Acid Transport (IBAT) inhibitor (including linerixibat) in the 3 months prior to screening.
• Past or intended use of over the counter or prescription medication, including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the Investigator in conjunction with GSK Medical Monitor.
• Current enrollment 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: 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than 4 new chemical entities within 12 months before the first dose in the current study.
• Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5x upper limit of normal (ULN).
• Bilirubin >1.5x ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody test or hepatitis C Ribonucleic acid (RNA) test at screening or within 3 months prior to first dose of study intervention.
• Positive human immunodeficiency virus (HIV) antibody test
• Fridericia's QT correction formula (QTcF) >450 msec on ECG performed at screening.
• Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.
• Regular alcohol consumption within 6 months prior to signing the informed consent.
• Regular use of tobacco- or nicotine-containing products in the 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence AB; Participants will receive linerixibat in fed state (Treatment A) in period 1 followed by linerixibat in fasted state (Treatment B) in period 2. The washout period will be of at least 7 days.	Drug: linerixibat; linerixibat will be administered per the treatment sequence
Experimental: Treatment sequence BA; Participants will receive linerixibat in fasted state (Treatment B) in period 1 followed by linerixibat in fed state (Treatment A) in period 2. The washout period will be of at least 7 days.	Drug: linerixibat; linerixibat will be administered per the treatment sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)]	Up to 36 hours post dose
Maximum observed plasma concentration (Cmax) of linerixibat	Up to 36 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to infinite time [AUC (0-∞)]	Up to 36 hours post dose
Plasma linerixibat area under the concentration-time curve from time zero (pre-dose) to 24 hour [AUC (0-24)]	Up to 24 hours post dose
Time of occurrence of Cmax (Tmax) of linerixibat	Up to 36 hours post dose
Delay in achieving Tmax (Tlag) of linerixibat	Up to 36 hours post dose
Apparent terminal phase half-life (t1/2) of linerixibat	Up to 36 hours post dose
Apparent clearance (CL/F) of linerixibat	Up to 36 hours post dose
Apparent terminal phase volume of distribution (Vz/F) of linerixibat	Up to 36 hours post dose
Serum C4 area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)]	Up to 36 hours post dose
Serum C4 area under the concentration-time curve from time zero (pre-dose) to 24 hour [AUC (0-24)]	Up to 24 hours post dose
Incidence of adverse events (AEs) and of serious adverse events (SAEs)	Up to day 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinincal Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Actual): October 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: June 22, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 24, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Food effect; Pharmacokinetic; Pharmacodynamic; Linerixibat; Ileal bile acid transporter (IBAT) inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: 214656

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No