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临床试验/NCT04053023
NCT04053023已完成1 期

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

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 19 人开始时间: 2019年8月27日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
入组人数
19
试验地点
1
主要终点
Part B- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Crossover
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 80 Years（Adult, Older Adult）
性别
All
接受健康志愿者
是

入选标准

  • •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.

排除标准

  • •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.

研究组 & 干预措施

Participants receiving obeticholic acid and linerixibat

Experimental

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.

干预措施: GSK2330672 (linerixibat) (Drug)

Participants receiving obeticholic acid and linerixibat

Experimental

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.

干预措施: Obeticholic acid (Drug)

结局指标

主要结局

Part B- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm

时间窗: 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

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

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

时间窗: 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

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- Average Trough Concentration (Ctrough) for Total-OCA at Steady State: OCA Arm

时间窗: 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

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 B- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm

时间窗: 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

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

Part A- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm

时间窗: 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

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

时间窗: 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

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

时间窗: 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

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 Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm

时间窗: 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

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

时间窗: 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

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

Part A- Maximum Observed Concentration (Cmax) for Total-OCA at Steady State: OCA Arm

时间窗: 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

Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Part B- AUC(0-24) for Total-OCA at Steady State: OCA Arm

时间窗: 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

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

时间窗: 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

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

Part A- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm

时间窗: 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

Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Part B- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm

时间窗: 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

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

时间窗: 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

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

时间窗: 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

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

次要结局

  • Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm(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)
  • Part A- AUC(0-t) for OCA: OCA Arm(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)
  • Part A- AUC(0-t) for OCA: OCA + Linerixibat Arm(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)
  • Part A- AUC(0-24) for OCA: OCA Arm(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)
  • Part A- Average Ctrough for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part A- Tmax for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part A- Cmax for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-24) for OCA: OCA + Linerixibat Arm(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)
  • Part B- Ctrough for OCA: OCA Arm(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)
  • Part B- Ctrough for OCA: OCA + Linerixibat Arm(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)
  • Part A- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total-OCA: OCA Arm(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)
  • Part A- Tmax for Total-OCA: OCA + Linerixibat Arm(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)
  • Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm(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)
  • Part A- AUC(0-24) for OCA: OCA + Linerixibat Arm(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)
  • Part A- Cmax for OCA: OCA + Linerixibat Arm(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)
  • Part A- Cmax for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part A- AUC(0-24) for Glyco-OCA: OCA Arm(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)
  • Part A- Cmax for Glyco-OCA: OCA Arm(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)
  • Part B- AUC(0-t) for OCA: OCA Arm(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)
  • Part B- Cmax for OCA: OCA + Linerixibat Arm(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)
  • Part A- Cmax for OCA: OCA Arm(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)
  • Part A- Average Ctrough for OCA: OCA Arm(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)
  • Part A- Average Ctrough for OCA: OCA + Linerixibat Arm(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)
  • Part A- Tmax for OCA: OCA Arm(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)
  • Part A- Tmax for OCA: OCA + Linerixibat Arm(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)
  • Part A- AUC(0-t) for Tauro-OCA: OCA Arm(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)
  • Part A- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part A- AUC(0-24) for Tauro-OCA: OCA Arm(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)
  • Part A- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part A- AUC(0-t) for Glyco-OCA: OCA Arm(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)
  • Part A- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part A- Cmax for Tauro-OCA: OCA Arm(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)
  • Part A- Tmax for Tauro-OCA: OCA Arm(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)
  • Part A- Average Ctrough for Tauro-OCA: OCA Arm(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)
  • Part A- Average Ctrough for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- Tmax for Total-OCA: OCA Arm(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)
  • Part B- Tmax for OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-24) for Tauro-OCA: OCA Arm(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)
  • Part B- Tmax for Tauro-OCA: OCA Arm(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)
  • Part B- Ctrough for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- Tmax for Glyco-OCA: OCA Arm(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)
  • Part A- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part A- Average Ctrough for Glyco-OCA: OCA Arm(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)
  • Part A- Tmax for Glyco-OCA: OCA Arm(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)
  • Part A- Tmax for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- Tmax for Total-OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-t) for OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-24) for OCA: OCA Arm(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)
  • Part B- Cmax for OCA: OCA Arm(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)
  • Part B- Tmax for OCA: OCA Arm(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)
  • Part B- Cmax for Tauro-OCA: OCA Arm(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)
  • Part B- Cmax for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-t) for Tauro-OCA: OCA Arm(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)
  • Part B- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-t) for Glyco-OCA: OCA Arm(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)
  • Part B- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-24) for Glyco-OCA: OCA Arm(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)
  • Part B- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- Cmax for Glyco-OCA: OCA Arm(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)
  • Part B- Ctrough for Glyco-OCA: OCA Arm(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)
  • Part B- Ctrough for Tauro-OCA: OCA Arm(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)
  • Part B- Ctrough for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part B- Tmax for Tauro-OCA: OCA + Linerixibat Arm(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)
  • Part B- Cmax for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part B- Tmax for Glyco-OCA: OCA + Linerixibat Arm(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)
  • Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Day 52)
  • Part B- Number of Participants With Any AEs and SAEs(Up to Day 52)
  • 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(Baseline (Day -1), and at Day 17)
  • Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Pulse Rate: OCA Arm(Baseline (Day -1), Days 1 and 17)
  • Part A- Change From Baseline in Respiratory Rate: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Body Temperature: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part B- Change From Baseline in Body Temperature(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm(Baseline (Day -1), and at Day 38)
  • Part B- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm(Baseline (Day -1), Days 1 and 17)
  • Part A- Change From Baseline in Pulse Rate: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part B- Change From Baseline in Pulse Rate(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Respiratory Rate: OCA Arm(Baseline (Day -1), Days 1 and 17)
  • Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Body Temperature: OCA Arm(Baseline (Day -1), Days 1 and 17)
  • Part B- Change From Baseline in SBP and DBP(Baseline (Day -1), and up to Day 38)
  • Part B- Change From Baseline in Respiratory Rate(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part B- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Baseline (Day -1), and up to Day 38)
  • Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Baseline (Day -1), and up to Day 38)
  • Part B- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part B- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea(Baseline (Day -1), and up to Day 38)
  • Part B- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin(Baseline (Day -1), and up to Day 38)
  • Part B- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline(Baseline (Day -1), and up to Day 38)
  • Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm(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)
  • Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part B- Change From Baseline in Hematology Parameter: Hemoglobin(Baseline (Day -1), and up to Day 38)
  • Part B- Change From Baseline in Hematology Parameter: Hematocrit(Baseline (Day -1), and up to Day 38)
  • Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Change From Baseline in Chemistry Parameter: Protein: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Change From Baseline in Chemistry Parameter: Protein: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm(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)
  • Part A- Tmax for Linerixibat: OCA + Linerixibat Arm(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)
  • Part B- Change From Baseline in Chemistry Parameters: ALT, ALP, AST(Baseline (Day -1), and up to Day 38)
  • Part B- Change From Baseline in Chemistry Parameter: Protein(Baseline (Day -1), and up to Day 38)
  • Part B- Cmax for Linerixibat: OCA + Linerixibat Arm(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)
  • Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm(Baseline (Day -1) and at Day 17)
  • Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm(Baseline (Day -1) and at Day 38)
  • Part A- Cmax for Linerixibat: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm(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)
  • Part B- AUC(0-12) for Linerixibat: OCA + Linerixibat Arm(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)
  • Part B- Tmax for Linerixibat: OCA + Linerixibat Arm(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)

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