Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Adult Participants

A Two-part, Phase 1, Open-label, Randomized, Parallel-arm, Fixed Sequence, Drug-drug Interaction Study to Investigate the Effect of Linerixibat on Plasma Concentrations of Obeticholic Acid and Conjugates in Healthy Adult Participants

This study aims to investigate the effect of linerixibat on plasma concentrations of obeticholic acid (OCA) and its conjugates in healthy adult participants to inform the potential for drug interaction with coadministration of linerixibat and OCA.

Study Overview

• Status: Completed
• Conditions: Pruritus
• Intervention / Treatment: Drug: Obeticholic acid; Drug: Linerixibat

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overtly healthy male or female participants 18 to 50 years of age inclusive, at the time of signing the informed consent
• Body weight greater than (>) 50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32 kilogram per meter square (kg/m^2) (inclusive)
• Capable of giving signed informed consent as the protocol.

Exclusion Criteria:

• Any active dermatologic disorder leading to or with the potential to cause itching or a recent history of unexplained clinically significant itching locally or generally within the prior 3 months
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) and/or confirmed hepatocellular carcinoma or biliary cancer
• History of gall bladder removal
• Current symptomatic gallstones or inflammatory gall bladder disease
• Significant history of or current disorders that can significantly alter 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) or Ocaliva 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
• Current enrolment in a clinical trial or recent participation in a clinical trial and has received an investigational product within 30 days before the first dose in the current study
• 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 >1.5xULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin lesser than (<)35%
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test or positive hepatitis C riboneucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
• Positive pregnancy test at screening or at Day -1
• Positive human immunodeficiency virus (HIV) antibody test
• QT interval corrected (QTc) >450 millisecond (msec)
• Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study
• Participants with moderate (or greater) alcohol consumption
• History of or regular use of tobacco- or nicotine-containing products in the 3 months prior to screening.
• Female participants unable or unwilling to comply with specific contraception restrictions as detailed in the protocol
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56-day period
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Arm 1; Participants will receive OCA at dose level 1, 4 hours after the linerixibat administration	Drug: Obeticholic acid; OCA will be administered; Drug: Linerixibat; Linerixibat will be administered
EXPERIMENTAL: Treatment Arm 2; Participants will receive OCA at dose level 2 along with linerixibat	Drug: Obeticholic acid; OCA will be administered; Drug: Linerixibat; Linerixibat will be administered
EXPERIMENTAL: Treatment Arm 3; Participants will receive OCA at dose level 1 along with linerixibat	Drug: Obeticholic acid; OCA will be administered; Drug: Linerixibat; Linerixibat will be administered
EXPERIMENTAL: Treatment Arm 4; Participants will receive OCA at dose level 2, 4 hours after the linerixibat administration	Drug: Obeticholic acid; OCA will be administered; Drug: Linerixibat; Linerixibat will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Average trough concentration (Ctrough) in plasma for total-OCA at steady state	Days 35 to 38

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration curve from time 0 to t (AUC0-t) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state	At Day 18 and Day 37
AUC from time 0 to 24 hour (AUC0-24) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state	Up to 24 hours on Day 18 and Day 37
Maximum observed plasma concentration (Cmax) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state	At Day 18 and Day 37
Average trough concentration (Ctrough) in plasma for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state	Days 17 to 19 and Days 35 to 38
Time to maximum concentration (Tmax) for OCA, tauro-OCA, glyco-OCA and total-OCA	At Day 18 and Day 37
Ctrough of total OCA over Days 17 to 19 and Days 35 to 38	Days 17 to 19 and Days 35 to 38
Number of participants with adverse events	Up to Day 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 23, 2021
• Primary Completion (ACTUAL): May 31, 2022
• Study Completion (ACTUAL): May 31, 2022

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (ACTUAL): November 24, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteers; Linerixibat; Drug-drug interaction; Obeticholic acid
• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: 213688

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; SAP; ICF; 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