Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Adult Participants

Pruritus Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05133830
• Other study ID #: 213688
• Status: Completed
• Phase: Phase 1
• Start date: November 23, 2021
• Est. completion date: May 31, 2022

Study information

• Verified date: November 2022
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: May 31, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pruritus

Intervention

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

Locations

Country	Name	City	State
United States	GSK Investigational Site	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average trough concentration (Ctrough) in plasma for total-OCA at steady state		Days 35 to 38
Secondary	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
Secondary	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
Secondary	Maximum observed plasma concentration (Cmax) for OCA, tauro-OCA, glyco-OCA and total-OCA at steady state		At Day 18 and Day 37
Secondary	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
Secondary	Time to maximum concentration (Tmax) for OCA, tauro-OCA, glyco-OCA and total-OCA		At Day 18 and Day 37
Secondary	Ctrough of total OCA over Days 17 to 19 and Days 35 to 38		Days 17 to 19 and Days 35 to 38
Secondary	Number of participants with adverse events		Up to Day 52