Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Adult Participants

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 4, 2022

Interventions

  • Drug: Obeticholic acid
    • OCA will be administered
  • Drug: Linerixibat
    • Linerixibat will be administered

Arms, Groups and Cohorts

  • Experimental: Treatment Arm 1
    • Participants will receive OCA at dose level 1, 4 hours after the linerixibat administration
  • Experimental: Treatment Arm 2
    • Participants will receive OCA at dose level 2 along with linerixibat
  • Experimental: Treatment Arm 3
    • Participants will receive OCA at dose level 1 along with linerixibat
  • Experimental: Treatment Arm 4
    • Participants will receive OCA at dose level 2, 4 hours after the linerixibat administration

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 50 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • GlaxoSmithKline
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • GSK Clinical Trials, Study Director, GlaxoSmithKline
  • Overall Contact(s)
    • US GSK Clinical Trials Call Center, 877-379-3718, GSKClinicalSupportHD@gsk.com

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