Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Adult Participants

NCT05133830 | Completed Phase 1 FDA Drug

• 1 other identifier: 213688
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pruritus

Keywords

Drug-drug interaction; Healthy Volunteers; Linerixibat; Obeticholic acid; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

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

  Days 35 to 38

Secondary Outcomes (7)

• 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

Study Arms (4)

Treatment Arm 1

EXPERIMENTAL

Participants will receive OCA at dose level 1, 4 hours after the linerixibat administration

Drug: Obeticholic acid; Drug: Linerixibat

Treatment Arm 2

EXPERIMENTAL

Participants will receive OCA at dose level 2 along with linerixibat

Drug: Obeticholic acid; Drug: Linerixibat

Treatment Arm 3

EXPERIMENTAL

Participants will receive OCA at dose level 1 along with linerixibat

Drug: Obeticholic acid; Drug: Linerixibat

Treatment Arm 4

EXPERIMENTAL

Participants will receive OCA at dose level 2, 4 hours after the linerixibat administration

Drug: Obeticholic acid; Drug: Linerixibat

Interventions

Obeticholic acid DRUG

OCA will be administered

Treatment Arm 1; Treatment Arm 2; Treatment Arm 3; Treatment Arm 4

Linerixibat DRUG

Linerixibat will be administered

Treatment Arm 1; Treatment Arm 2; Treatment Arm 3; Treatment Arm 4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Pruritus

Interventions

obeticholic acid

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Two arms will be evaluated in parallel in Part A. After Part A, if Part B is conducted, one of the two remaining arms will be evaluated.

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: November 24, 2021
• Study Start: November 23, 2021
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (1)