Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects

NCT ID: NCT04053023

Last Updated: 2020-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-27
• Study Completion Date: 2019-11-25

Brief Summary

In participants with inadequate response/intolerance to ursodeoxycholic acid (UDCA) taking obeticholic acid (OCA) who experience pruritus (due to primary biliary cholangitis [PBC], OCA, or both) the addition of linerixibat to OCA therapy may be considered following marketing approval. It is therefore important to characterize any potential effect of linerixibat on the pharmacokinetics of OCA in humans at clinically relevant dosages. Accordingly, a drug-drug interaction (DDI) study with linerixibat (potential perpetrator) and OCA (potential victim) will be conducted to inform both future clinical trials with linerixibat and the potential concomitant administration of these drugs in a clinical setting. This is a single-center, one part (with optional second part) open-label, single sequence crossover, drug interaction study to investigate the effect of linerixibat on plasma concentrations of OCA and OCA conjugates in healthy participants. Approximately 19 participants will be enrolled in part A and further 19 participants in part B (if performed) in the study and will have a phone call follow-up till 7-14 days post-last linerixibat dose.

Conditions

Cholestasis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants receiving obeticholic acid and linerixibat

In Part A, participants will be administered one tablet of 10 milligrams (mg) obeticholic acid once daily continuously for 37 days (study Day 1 to study Day 37). Two tablets of 45 mg linerixibat will be administered twice daily from study Day 20 to study Day 37. 1 tablet of 45 mg linerixibat will be administered on Day 38. After evaluation of Part A, if optional part B is conducted, participants will be administered linerixibat and obeticholic acid at an alternative dosing regimen.

Group Type: EXPERIMENTAL

GSK2330672 (linerixibat)

Intervention Type: DRUG

GSK2330672 is available as a tablet with unit dose strength of 45 mg.

Obeticholic acid

Intervention Type: DRUG

Obeticholic acid is available as a tablet with a unit dose strength of 10 mg (or 5 mg dependent on evaluation of Part A).

Interventions

GSK2330672 (linerixibat)

GSK2330672 is available as a tablet with unit dose strength of 45 mg.

Intervention Type: DRUG

Obeticholic acid

Obeticholic acid is available as a tablet with a unit dose strength of 10 mg (or 5 mg dependent on evaluation of Part A).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Between 18 and 80 years of age inclusive, at the time of signing the informed consent.
• Healthy, as determined by the investigator or medically qualified designee, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG. A participant with a clinical abnormality or laboratory parameter (i.e., outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees in consultation with the GlaxoSmithKline (GSK) medical monitor and documents in the source documentation that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes.
• Body weight > 50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 32 kg per square meter (inclusive).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
• Male and female- A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

Exclusion Criteria

• Any active dermatologic disorder leading to or with the potential to cause pruritus 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
• Participants with a history of cholecystectomy
• Current symptomatic cholelithiasis or inflammatory gall bladder disease
• Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
• Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history) clinical laboratory tests, or 12-lead ECG
• Current episode, recent history (within 1 month of screening visit), or chronic history of clinically significant diarrhea
• Lymphoma, leukaemia, or 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
• Any current medical condition (e.g. psychiatric disorder, senility, dementia, or other condition), clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study
• Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study
• Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 gram of alcohol: a glass (approximately [~] 240 milliliter [mL]) of beer, 1 small glass (~100 mL) of wine or 1 (~25 mL) measure of spirits
• History of or regular use of tobacco- or nicotine-containing products (confirmed by smokerlyzer test) in the 3 months prior to screening.
• Administration of any IBAT inhibitor (including linerixibat) or OCA 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 medical monitor.
• Current enrollment in a clinical trial, recent participation in a clinical trial and has received an investigational product within 30 days (or 5 half-lives of previous trial intervention, whichever is longer) 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 ALT or AST >1.5 times the upper limit of normal (ULN)
• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening or within 3 months of the screening visit
• Positive serum pregnancy test at screening or positive urine pregnancy test at admission in WOCBP only
• Positive human immunodeficiency virus (HIV) antibody test
• QTc >450 millisecond (msec) on ECG performed at screening.
• Positive pre-study drug/alcohol screen or positive drug/alcohol screen at any time during the study.
• Female participants unable or unwilling to comply with specific contraception restrictions.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
• Unwillingness or inability to follow the procedures outlined in the protocol for the expected duration of study participation.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Cambridge, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

206224

Identifier Type: -

Identifier Source: org_study_id