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Completed

NCT Number: NCT05133830

Linerixibat and Obeticholic Acid Drug Interaction Study 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.

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Key information

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Obeticholic acid

Drug

OCA will be administered

Linerixibat

Drug

Linerixibat will be administered

Primary outcomes

  1. Average trough concentration (Ctrough) in plasma for total-OCA at steady state

    Time frame: Days 35 to 38

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. Time to maximum concentration (Tmax) for OCA, tauro-OCA, glyco-OCA and total-OCA

    Time frame: At Day 18 and Day 37

  6. 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

  7. Number of participants with adverse events

    Time frame: Up to Day 52

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Nov 24, 2021
Registry last updated
Nov 8, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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