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Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects

Primary Purpose

Cholestasis

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK2330672 (linerixibat)
Obeticholic acid
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cholestasis focused on measuring linerixibat (GSK2330672), obeticholic acid, drug interaction, primary biliary cholangitis, pharmacokinetics

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participants receiving obeticholic acid and linerixibat

Arm Description

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.

Outcomes

Primary Outcome Measures

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
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Pharmacokinetic (PK) Parameters Population consisted of all participants for whom pharmacokinetic parameters were derivable.
Part A- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
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
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Maximum Observed Concentration (Cmax) for Total-OCA at Steady State: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Average Trough Concentration (Ctrough) for Total-OCA at Steady State: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Part A- Average Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Part B- AUC(0-t) for Total-OCA at Steady State: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- AUC(0-24) for Total-OCA at Steady State: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- Cmax for Total-OCA at Steady State: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- Ctrough for Total-OCA at Steady State: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.

Secondary Outcome Measures

Part A- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Tmax for Total-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-t) for OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-t) for OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Average Ctrough for OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Part A- Average Ctrough for OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Part A- Tmax for OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Tmax for OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-t) for Tauro-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for Tauro-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for Tauro-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Average Ctrough for Tauro-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Part A- Average Ctrough for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Part A- Tmax for Tauro-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Tmax for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-t) for Glyco-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for Glyco-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for Glyco-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Cmax for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Average Ctrough for Glyco-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Part A- Average Ctrough for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Part A- Tmax for Glyco-OCA: OCA Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part A- Tmax for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Part B- Tmax for Total-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- Tmax for Total-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Part B- AUC(0-t) for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- AUC(0-t) for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- AUC(0-24) for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- AUC(0-24) for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- Cmax for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- Cmax for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- Ctrough for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- Ctrough for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- Tmax for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- Tmax for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Part B- AUC(0-t) for Tauro-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- AUC(0-24) for Tauro-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- Cmax for Tauro-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- Cmax for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- Ctrough for Tauro-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- Ctrough for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- Tmax for Tauro-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- Tmax for Tauro-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Part B- AUC(0-t) for Glyco-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- AUC(0-24) for Glyco-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- Cmax for Glyco-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- Cmax for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- Ctrough for Glyco-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- Ctrough for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- Tmax for Glyco-OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part B- Tmax for Glyco-OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. All Participants Population consisted of all participants who took at least 1 dose of study intervention.
Part B- Number of Participants With Any AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
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
Twelve lead electrocardiograms (ECGs) were obtained to measure PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 5 minutes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm
Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 5 minutes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part B- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF
Twelve lead ECGs were planned to be measured PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were planned to be performed with the participant in a supine position after a rest of at least 5 minutes.
Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm
SBP and DBP were measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm
SBP and DBP were measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Pulse Rate: OCA Arm
Pulse rate was measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Pulse Rate: OCA + Linerixibat Arm
Pulse rate was measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Respiratory Rate: OCA Arm
Respiratory rate was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Respiratory Rate: OCA + Linerixibat Arm
Respiratory rate was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Body Temperature: OCA Arm
Body temperature was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Body Temperature: OCA + Linerixibat Arm
Body temperature was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part B- Change From Baseline in SBP and DBP
SBP and DBP were planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Part B- Change From Baseline in Pulse Rate
Pulse rate was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Part B- Change From Baseline in Respiratory Rate
Respiratory rate was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Part B- Change From Baseline in Body Temperature
Body temperature was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA Arm
Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA + Linerixibat Arm
Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA Arm
Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA + Linerixibat Arm
Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA Arm
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA + Linerixibat Arm
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA Arm
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA + Linerixibat Arm
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm
Blood samples were collected to analyze the hematology parameters: erythrocytes and reticulocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm
Blood samples were collected to analyze the hematology parameters: erythrocytes and reticulocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part B- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes
Blood samples were planned to be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes.
Part B- Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were planned to be collected to analyze the hematology parameter: hemoglobin.
Part B- Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were planned to be collected to analyze the hematology parameter: hematocrit.
Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were planned to be collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin.
Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were planned to be collected to analyze the hematology parameter: erythrocytes mean corpuscular volume.
Part B- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes
Blood samples were planned to be collected to analyze the hematology parameters: erythrocytes and reticulocytes.
Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm
Blood samples were collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm
Blood samples were collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm
Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm
Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameter: Protein: OCA Arm
Blood samples were collected to analyze the chemistry parameter: protein. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part A- Change From Baseline in Chemistry Parameter: Protein: OCA + Linerixibat Arm
Blood samples were collected to analyze the chemistry parameter: protein. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part B- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea
Blood samples were planned to be collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea.
Part B- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin
Blood samples were planned to be collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin.
Part B- Change From Baseline in Chemistry Parameters: ALT, ALP, AST
Blood samples were planned to be collected to analyze the chemistry parameters: ALT, ALP and AST.
Part B- Change From Baseline in Chemistry Parameter: Protein
Blood samples were planned to be collected to analyze the chemistry parameter: protein.
Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm
Urine samples were collected from participants for urinalysis for measuring potential of hydrogen (pH) and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes and were counted as cells per high-power field (cells/HPF). Baseline was considered as Day -1. Number of participants with worst case urinalysis result by microscopic examination have been presented.
Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm
Urine samples were collected from participants for urinalysis for measuring pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes and were counted as cells/HPF. Baseline was considered as Day -1. Number of participants with worst case urinalysis result by microscopic examination have been presented.
Part B- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline
Urine samples were planned to be collected from participants for urinalysis for measuring pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was planned to be sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes.
Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Part A- Cmax for Linerixibat: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Part A- Tmax for Linerixibat: OCA + Linerixibat Arm
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Part B- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Part B- AUC(0-12) for Linerixibat: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Part B- Cmax for Linerixibat: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Part B- Tmax for Linerixibat: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.

Full Information

First Posted
August 8, 2019
Last Updated
July 1, 2020
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT04053023
Brief Title
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

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
August 27, 2019 (Actual)
Primary Completion Date
November 25, 2019 (Actual)
Study Completion Date
November 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholestasis
Keywords
linerixibat (GSK2330672), obeticholic acid, drug interaction, primary biliary cholangitis, pharmacokinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
This will be a non-randomized study. Eligible subjects will receive OCA and OCA+linerixibat in a fixed sequence.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Participants receiving obeticholic acid and linerixibat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GSK2330672 (linerixibat)
Intervention Description
GSK2330672 is available as a tablet with unit dose strength of 45 mg.
Intervention Type
Drug
Intervention Name(s)
Obeticholic acid
Intervention Description
Obeticholic acid is available as a tablet with a unit dose strength of 10 mg (or 5 mg dependent on evaluation of Part A).
Primary Outcome Measure Information:
Title
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
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Pharmacokinetic (PK) Parameters Population consisted of all participants for whom pharmacokinetic parameters were derivable.
Time Frame
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
Title
Part A- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
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
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Maximum Observed Concentration (Cmax) for Total-OCA at Steady State: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Average Trough Concentration (Ctrough) for Total-OCA at Steady State: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Time Frame
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
Title
Part A- Average Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Time Frame
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
Title
Part B- AUC(0-t) for Total-OCA at Steady State: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- AUC(0-24) for Total-OCA at Steady State: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- Cmax for Total-OCA at Steady State: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- Ctrough for Total-OCA at Steady State: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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 Outcome Measure Information:
Title
Part A- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Tmax for Total-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-t) for OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-t) for OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Average Ctrough for OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Time Frame
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
Title
Part A- Average Ctrough for OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Time Frame
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
Title
Part A- Tmax for OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Tmax for OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-t) for Tauro-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for Tauro-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for Tauro-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Average Ctrough for Tauro-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Time Frame
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
Title
Part A- Average Ctrough for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Time Frame
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
Title
Part A- Tmax for Tauro-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Tmax for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-t) for Glyco-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for Glyco-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for Glyco-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Cmax for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Average Ctrough for Glyco-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented.
Time Frame
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
Title
Part A- Average Ctrough for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented.
Time Frame
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
Title
Part A- Tmax for Glyco-OCA: OCA Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part A- Tmax for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame
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
Title
Part B- Tmax for Total-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- Tmax for Total-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA.
Time Frame
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
Title
Part B- AUC(0-t) for OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- AUC(0-t) for OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- AUC(0-24) for OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- AUC(0-24) for OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- Cmax for OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- Cmax for OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- Ctrough for OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- Ctrough for OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- Tmax for OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- Tmax for OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time Frame
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
Title
Part B- AUC(0-t) for Tauro-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- AUC(0-24) for Tauro-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- Cmax for Tauro-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- Cmax for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- Ctrough for Tauro-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- Ctrough for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- Tmax for Tauro-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- Tmax for Tauro-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA.
Time Frame
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
Title
Part B- AUC(0-t) for Glyco-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- AUC(0-24) for Glyco-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- Cmax for Glyco-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- Cmax for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- Ctrough for Glyco-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- Ctrough for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- Tmax for Glyco-OCA: OCA Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part B- Tmax for Glyco-OCA: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA.
Time Frame
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
Title
Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. All Participants Population consisted of all participants who took at least 1 dose of study intervention.
Time Frame
Up to Day 52
Title
Part B- Number of Participants With Any AEs and SAEs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
Time Frame
Up to Day 52
Title
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
Description
Twelve lead electrocardiograms (ECGs) were obtained to measure PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 5 minutes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1), and at Day 17
Title
Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm
Description
Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 5 minutes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1), and at Day 38
Title
Part B- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF
Description
Twelve lead ECGs were planned to be measured PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were planned to be performed with the participant in a supine position after a rest of at least 5 minutes.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm
Description
SBP and DBP were measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1), Days 1 and 17
Title
Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm
Description
SBP and DBP were measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Pulse Rate: OCA Arm
Description
Pulse rate was measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1), Days 1 and 17
Title
Part A- Change From Baseline in Pulse Rate: OCA + Linerixibat Arm
Description
Pulse rate was measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Respiratory Rate: OCA Arm
Description
Respiratory rate was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1), Days 1 and 17
Title
Part A- Change From Baseline in Respiratory Rate: OCA + Linerixibat Arm
Description
Respiratory rate was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Body Temperature: OCA Arm
Description
Body temperature was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1), Days 1 and 17
Title
Part A- Change From Baseline in Body Temperature: OCA + Linerixibat Arm
Description
Body temperature was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part B- Change From Baseline in SBP and DBP
Description
SBP and DBP were planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Pulse Rate
Description
Pulse rate was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Respiratory Rate
Description
Respiratory rate was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Body Temperature
Description
Body temperature was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm
Description
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA Arm
Description
Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA Arm
Description
Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA Arm
Description
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA Arm
Description
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm
Description
Blood samples were collected to analyze the hematology parameters: erythrocytes and reticulocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the hematology parameters: erythrocytes and reticulocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part B- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes
Description
Blood samples were planned to be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Hematology Parameter: Hemoglobin
Description
Blood samples were planned to be collected to analyze the hematology parameter: hemoglobin.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Hematology Parameter: Hematocrit
Description
Blood samples were planned to be collected to analyze the hematology parameter: hematocrit.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Description
Blood samples were planned to be collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Description
Blood samples were planned to be collected to analyze the hematology parameter: erythrocytes mean corpuscular volume.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes
Description
Blood samples were planned to be collected to analyze the hematology parameters: erythrocytes and reticulocytes.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm
Description
Blood samples were collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm
Description
Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm
Description
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part A- Change From Baseline in Chemistry Parameter: Protein: OCA Arm
Description
Blood samples were collected to analyze the chemistry parameter: protein. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Change From Baseline in Chemistry Parameter: Protein: OCA + Linerixibat Arm
Description
Blood samples were collected to analyze the chemistry parameter: protein. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part B- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea
Description
Blood samples were planned to be collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin
Description
Blood samples were planned to be collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Chemistry Parameters: ALT, ALP, AST
Description
Blood samples were planned to be collected to analyze the chemistry parameters: ALT, ALP and AST.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part B- Change From Baseline in Chemistry Parameter: Protein
Description
Blood samples were planned to be collected to analyze the chemistry parameter: protein.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm
Description
Urine samples were collected from participants for urinalysis for measuring potential of hydrogen (pH) and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes and were counted as cells per high-power field (cells/HPF). Baseline was considered as Day -1. Number of participants with worst case urinalysis result by microscopic examination have been presented.
Time Frame
Baseline (Day -1) and at Day 17
Title
Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm
Description
Urine samples were collected from participants for urinalysis for measuring pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes and were counted as cells/HPF. Baseline was considered as Day -1. Number of participants with worst case urinalysis result by microscopic examination have been presented.
Time Frame
Baseline (Day -1) and at Day 38
Title
Part B- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline
Description
Urine samples were planned to be collected from participants for urinalysis for measuring pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was planned to be sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes.
Time Frame
Baseline (Day -1), and up to Day 38
Title
Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Time Frame
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
Title
Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Time Frame
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
Title
Part A- Cmax for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Time Frame
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
Title
Part A- Tmax for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods.
Time Frame
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
Title
Part B- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Time Frame
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
Title
Part B- AUC(0-12) for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Time Frame
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
Title
Part B- Cmax for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Time Frame
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
Title
Part B- Tmax for Linerixibat: OCA + Linerixibat Arm
Description
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Cambridge
ZIP/Postal Code
CB2 0GG
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
IPD Sharing 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.
IPD Sharing URL
http://clinicalstudydatarequest.com

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Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects

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