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CholestasisPhase 1NCT04053023

Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects

A Phase 1 study testing GSK2330672 (linerixibat) and Obeticholic acid in people with Cholestasis, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Cholestasis
What is being tested?
GSK2330672 (linerixibat) and Obeticholic acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited Kingdom
Study dates
27 Aug 2019to 25 Nov 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    Cambridge, CB2 0GG

Other trials in United Kingdom

About this study

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

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

Conditions
Cholestasis
Being tested
GSK2330672 (linerixibat), Obeticholic acid
Keywords
linerixibat (GSK2330672), obeticholic acid, drug interaction, primary biliary cholangitis, pharmacokinetics
Medical subject headings
Cholestasis, Liver Cirrhosis, Biliary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2330672 (linerixibat)Drug

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

  • Obeticholic acidDrug

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

Study groups in NCT04053023
Study groupRoleWhat they receive
Participants receiving obeticholic acid and linerixibatExperimentalIn 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.
Receives: Drug: GSK2330672 (linerixibat); Drug: Obeticholic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 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

  7. 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.

    Measured: 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

  8. 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.

    Measured: 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

  9. 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.

    Measured: 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

  10. 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.

    Measured: 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

  11. 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.

    Measured: 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

  12. 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.

    Measured: 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

  13. 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.

    Measured: 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

  14. 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.

    Measured: 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

  15. 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.

    Measured: 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

  16. 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.

    Measured: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose

Secondary outcomes (124)

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 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

  7. 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.

    Measured: 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

  8. 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.

    Measured: 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

  9. 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.

    Measured: 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

  10. 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.

    Measured: 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

  11. 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.

    Measured: 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

  12. 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.

    Measured: 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

  13. 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.

    Measured: 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

  14. 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.

    Measured: 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

  15. 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.

    Measured: 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

  16. 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.

    Measured: 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

  17. 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.

    Measured: 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

  18. 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.

    Measured: 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

  19. 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.

    Measured: 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

  20. 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.

    Measured: 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

  21. 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.

    Measured: 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

  22. 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.

    Measured: 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

  23. 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.

    Measured: 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

  24. 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.

    Measured: 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

  25. 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.

    Measured: 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

  26. 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.

    Measured: 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

  27. 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.

    Measured: 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

  28. 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.

    Measured: 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

  29. 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.

    Measured: 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

  30. 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.

    Measured: 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

  31. 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.

    Measured: 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

  32. 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.

    Measured: 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

  33. 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.

    Measured: 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

  34. 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.

    Measured: 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

  35. 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.

    Measured: 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

  36. 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.

    Measured: 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

  37. 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.

    Measured: 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

  38. 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.

    Measured: 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

  39. 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.

    Measured: 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

  40. 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.

    Measured: 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

  41. Part B- Cmax for OCA: OCA Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.

    Measured: 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

  42. Part B- Cmax for OCA: OCA + Linerixibat Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.

    Measured: 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

  43. Part B- Ctrough for OCA: OCA Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.

    Measured: 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

  44. Part B- Ctrough for OCA: OCA + Linerixibat Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.

    Measured: 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

  45. Part B- Tmax for OCA: OCA Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.

    Measured: 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

  46. Part B- Tmax for OCA: OCA + Linerixibat Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.

    Measured: 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

  47. 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.

    Measured: 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

  48. 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.

    Measured: 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

  49. 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.

    Measured: 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

  50. 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.

    Measured: 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

  51. 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.

    Measured: 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

  52. 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.

    Measured: 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

  53. 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.

    Measured: 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

  54. 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.

    Measured: 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

  55. 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.

    Measured: 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

  56. 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.

    Measured: 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

  57. 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.

    Measured: 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

  58. 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.

    Measured: 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

  59. 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.

    Measured: 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

  60. 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.

    Measured: 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

  61. 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.

    Measured: 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

  62. 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.

    Measured: 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

  63. 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.

    Measured: 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

  64. 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.

    Measured: 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

  65. 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.

    Measured: 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

  66. 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.

    Measured: 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

  67. 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.

    Measured: Up to Day 52

  68. 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.

    Measured: Up to Day 52

  69. 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.

    Measured: Baseline (Day -1), and at Day 17

  70. 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.

    Measured: Baseline (Day -1), and at Day 38

  71. 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.

    Measured: Baseline (Day -1), and up to Day 38

  72. 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.

    Measured: Baseline (Day -1), Days 1 and 17

  73. 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.

    Measured: Baseline (Day -1) and at Day 38

  74. 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.

    Measured: Baseline (Day -1), Days 1 and 17

  75. 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.

    Measured: Baseline (Day -1) and at Day 38

  76. 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.

    Measured: Baseline (Day -1), Days 1 and 17

  77. 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.

    Measured: Baseline (Day -1) and at Day 38

  78. 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.

    Measured: Baseline (Day -1), Days 1 and 17

  79. 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.

    Measured: Baseline (Day -1) and at Day 38

  80. 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.

    Measured: Baseline (Day -1), and up to Day 38

  81. 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.

    Measured: Baseline (Day -1), and up to Day 38

  82. 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.

    Measured: Baseline (Day -1), and up to Day 38

  83. 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.

    Measured: Baseline (Day -1), and up to Day 38

  84. 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.

    Measured: Baseline (Day -1) and at Day 17

  85. 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.

    Measured: Baseline (Day -1) and at Day 38

  86. 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.

    Measured: Baseline (Day -1) and at Day 17

  87. 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.

    Measured: Baseline (Day -1) and at Day 38

  88. 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.

    Measured: Baseline (Day -1) and at Day 17

  89. 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.

    Measured: Baseline (Day -1) and at Day 38

  90. 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.

    Measured: Baseline (Day -1) and at Day 17

  91. 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.

    Measured: Baseline (Day -1) and at Day 38

  92. 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.

    Measured: Baseline (Day -1) and at Day 17

  93. 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.

    Measured: Baseline (Day -1) and at Day 38

  94. 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.

    Measured: Baseline (Day -1) and at Day 17

  95. 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.

    Measured: Baseline (Day -1) and at Day 38

  96. 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.

    Measured: Baseline (Day -1), and up to Day 38

  97. Part B- Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were planned to be collected to analyze the hematology parameter: hemoglobin.

    Measured: Baseline (Day -1), and up to Day 38

  98. Part B- Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were planned to be collected to analyze the hematology parameter: hematocrit.

    Measured: Baseline (Day -1), and up to Day 38

  99. 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.

    Measured: Baseline (Day -1), and up to Day 38

  100. 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.

    Measured: Baseline (Day -1), and up to Day 38

  101. 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.

    Measured: Baseline (Day -1), and up to Day 38

  102. 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.

    Measured: Baseline (Day -1) and at Day 17

  103. 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.

    Measured: Baseline (Day -1) and at Day 38

  104. 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.

    Measured: Baseline (Day -1) and at Day 17

  105. 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.

    Measured: Baseline (Day -1) and at Day 38

  106. 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.

    Measured: Baseline (Day -1) and at Day 17

  107. 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.

    Measured: Baseline (Day -1) and at Day 38

  108. 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.

    Measured: Baseline (Day -1) and at Day 17

  109. 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.

    Measured: Baseline (Day -1) and at Day 38

  110. 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.

    Measured: Baseline (Day -1), and up to Day 38

  111. 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.

    Measured: Baseline (Day -1), and up to Day 38

  112. 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.

    Measured: Baseline (Day -1), and up to Day 38

  113. Part B- Change From Baseline in Chemistry Parameter: Protein

    Blood samples were planned to be collected to analyze the chemistry parameter: protein.

    Measured: Baseline (Day -1), and up to Day 38

  114. 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.

    Measured: Baseline (Day -1) and at Day 17

  115. 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.

    Measured: Baseline (Day -1) and at Day 38

  116. 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.

    Measured: Baseline (Day -1), and up to Day 38

  117. 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.

    Measured: 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

  118. 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.

    Measured: 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

  119. 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.

    Measured: 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

  120. 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.

    Measured: 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

  121. 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.

    Measured: 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

  122. 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.

    Measured: 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

  123. Part B- Cmax for Linerixibat: OCA + Linerixibat Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.

    Measured: 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

  124. Part B- Tmax for Linerixibat: OCA + Linerixibat Arm

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2019
  2. Study start27 Aug 2019
  3. Primary completion25 Nov 2019
  4. Study completion25 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
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)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04053023
Sponsor's protocol ID
206224
Status last verified
Jun 2020
First submitted
8 Aug 2019
Last updated
24 Jul 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2330672 (linerixibat) and Obeticholic acid in people with Cholestasis, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A- Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-t]) for Total-OCA at Steady State: OCA Arm (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). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04053023.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2020.

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