Clinical trial NCT04053023: Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects
Official title: An Open-label, Single Sequence Crossover, Drug Interaction Study to Investigate the Effect of Linerixibat (GSK2330672) on Plasma Concentrations of Obeticholic Acid and Conjugates in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cholestasis
Keywords: linerixibat (GSK2330672), obeticholic acid, drug interaction, primary biliary cholangitis, pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-08-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be a non-randomized study. Eligible subjects will receive OCA and OCA+linerixibat in a fixed sequence.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part A- Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-t]) for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Area Under the Concentration-time Curve From Time 0 to 24 Hour (AUC[0-24]) for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Maximum Observed Concentration (Cmax) for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Average Trough Concentration (Ctrough) for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Average Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-t) for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-24) for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Cmax for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Ctrough for Total-OCA at Steady State: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Secondary outcomes:
measure: Part A- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Tmax for Total-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 hours and 24 hours (Day 19) post-dose
measure: Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 hours and 24 hours (Day 38) post-dose
measure: Part A- AUC(0-t) for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-t) for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- AUC(0-24) for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-24) for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Cmax for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Cmax for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Average Ctrough for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Average Ctrough for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Tmax for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Tmax for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- AUC(0-t) for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- AUC(0-24) for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Cmax for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Cmax for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Average Ctrough for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Average Ctrough for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Tmax for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Tmax for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- AUC(0-t) for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- AUC(0-24) for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Cmax for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Cmax for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Average Ctrough for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Average Ctrough for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Tmax for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part A- Tmax for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Tmax for Total-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Tmax for Total-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-t) for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-t) for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-24) for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-24) for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Cmax for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Cmax for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Ctrough for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Ctrough for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Tmax for OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Tmax for OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-t) for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-24) for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Cmax for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Cmax for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Ctrough for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Ctrough for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Tmax for Tauro-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Tmax for Tauro-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-t) for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- AUC(0-24) for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Cmax for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Cmax for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Ctrough for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Ctrough for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part B- Tmax for Glyco-OCA: OCA Arm
timeFrame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
measure: Part B- Tmax for Glyco-OCA: OCA + Linerixibat Arm
timeFrame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
measure: Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 52
measure: Part B- Number of Participants With Any AEs and SAEs
timeFrame: Up to Day 52
measure: Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected Using Bazzet's Formula (QTcB), Corrected QT Interval Using Fredericia's Formula (QTcF): OCA Arm
timeFrame: Baseline (Day -1), and at Day 17
measure: Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1), and at Day 38
measure: Part B- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm
timeFrame: Baseline (Day -1), Days 1 and 17
measure: Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Pulse Rate: OCA Arm
timeFrame: Baseline (Day -1), Days 1 and 17
measure: Part A- Change From Baseline in Pulse Rate: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Respiratory Rate: OCA Arm
timeFrame: Baseline (Day -1), Days 1 and 17
measure: Part A- Change From Baseline in Respiratory Rate: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Body Temperature: OCA Arm
timeFrame: Baseline (Day -1), Days 1 and 17
measure: Part A- Change From Baseline in Body Temperature: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part B- Change From Baseline in SBP and DBP
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Pulse Rate
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Respiratory Rate
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Body Temperature
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part B- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part A- Change From Baseline in Chemistry Parameter: Protein: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Change From Baseline in Chemistry Parameter: Protein: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part B- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Chemistry Parameters: ALT, ALP, AST
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part B- Change From Baseline in Chemistry Parameter: Protein
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm
timeFrame: Baseline (Day -1) and at Day 17
measure: Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm
timeFrame: Baseline (Day -1) and at Day 38
measure: Part B- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline
timeFrame: Baseline (Day -1), and up to Day 38
measure: Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part A- Cmax for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part A- Tmax for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part B- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part B- AUC(0-12) for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part B- Cmax for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
measure: Part B- Tmax for Linerixibat: OCA + Linerixibat Arm
timeFrame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: