Cholestasis
Conditions
Keywords
linerixibat (GSK2330672), obeticholic acid, drug interaction, primary biliary cholangitis, pharmacokinetics
Brief summary
In participants with inadequate response/intolerance to ursodeoxycholic acid (UDCA) taking obeticholic acid (OCA) who experience pruritus (due to primary biliary cholangitis \[PBC\], OCA, or both) the addition of linerixibat to OCA therapy may be considered following marketing approval. It is therefore important to characterize any potential effect of linerixibat on the pharmacokinetics of OCA in humans at clinically relevant dosages. Accordingly, a drug-drug interaction (DDI) study with linerixibat (potential perpetrator) and OCA (potential victim) will be conducted to inform both future clinical trials with linerixibat and the potential concomitant administration of these drugs in a clinical setting. This is a single-center, one part (with optional second part) open-label, single sequence crossover, drug interaction study to investigate the effect of linerixibat on plasma concentrations of OCA and OCA conjugates in healthy participants. Approximately 19 participants will be enrolled in part A and further 19 participants in part B (if performed) in the study and will have a phone call follow-up till 7-14 days post-last linerixibat dose.
Interventions
DRUGGSK2330672 (linerixibat)
GSK2330672 is available as a tablet with unit dose strength of 45 mg.
DRUGObeticholic acid
Obeticholic acid is available as a tablet with a unit dose strength of 10 mg (or 5 mg dependent on evaluation of Part A).
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This will be a non-randomized study. Eligible subjects will receive OCA and OCA+linerixibat in a fixed sequence.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 80 years of age inclusive, at the time of signing the informed consent. * Healthy, as determined by the investigator or medically qualified designee, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG. A participant with a clinical abnormality or laboratory parameter (i.e., outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees in consultation with the GlaxoSmithKline (GSK) medical monitor and documents in the source documentation that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes. * Body weight \> 50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 32 kg per square meter (inclusive). * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. * Male and female- A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Exclusion criteria
* Any active dermatologic disorder leading to or with the potential to cause pruritus or a recent history of unexplained clinically significant itching locally or generally within the prior 3 months * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) and/or confirmed hepatocellular carcinoma or biliary cancer * Participants with a history of cholecystectomy * Current symptomatic cholelithiasis or inflammatory gall bladder disease * Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data * Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history) clinical laboratory tests, or 12-lead ECG * Current episode, recent history (within 1 month of screening visit), or chronic history of clinically significant diarrhea * Lymphoma, leukaemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years * Any current medical condition (e.g. psychiatric disorder, senility, dementia, or other condition), clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study * Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study * Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of \>14 units for females and \>21 units for males. One unit is equivalent to 8 gram of alcohol: a glass (approximately \[\ \] 240 milliliter \[mL\]) of beer, 1 small glass (\ 100 mL) of wine or 1 (\ 25 mL) measure of spirits * History of or regular use of tobacco- or nicotine-containing products (confirmed by smokerlyzer test) in the 3 months prior to screening. * Administration of any IBAT inhibitor (including linerixibat) or OCA in the 3 months prior to screening * Past or intended use of over-the-counter or prescription medication (including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the investigator in conjunction with GSK medical monitor. * Current enrollment in a clinical trial, recent participation in a clinical trial and has received an investigational product within 30 days (or 5 half-lives of previous trial intervention, whichever is longer) before the first dose in the current study * Exposure to more than 4 new chemical entities within 12 months before the first dose in the current study. * Screening ALT or AST \>1.5 times the upper limit of normal (ULN) * Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) * Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening or within 3 months of the screening visit * Positive serum pregnancy test at screening or positive urine pregnancy test at admission in WOCBP only * Positive human immunodeficiency virus (HIV) antibody test * QTc \>450 millisecond (msec) on ECG performed at screening. * Positive pre-study drug/alcohol screen or positive drug/alcohol screen at any time during the study. * Female participants unable or unwilling to comply with specific contraception restrictions. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period. * Unwillingness or inability to follow the procedures outlined in the protocol for the expected duration of study participation. * Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B- AUC(0-t) for Total-OCA at Steady State: 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 | 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 | 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- AUC(0-t) for Total-OCA at Steady State: 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 | 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 | 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 | 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- Maximum Observed Concentration (Cmax) for Total-OCA at Steady State: 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm | 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 Trough Concentration (Ctrough) for Total-OCA at Steady State: 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented. |
| Part A- Average Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm | 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 + 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA. |
| Part B- AUC(0-24) for Total-OCA at Steady State: OCA Arm | 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- AUC(0-24) for Total-OCA at Steady State: 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 | 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 | 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 + 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- AUC(0-24) for Tauro-OCA: OCA Arm | 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 tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Cmax for Tauro-OCA: OCA Arm | 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 tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Average Ctrough for Tauro-OCA: OCA Arm | 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 tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented. |
| Part A- Average Ctrough for Tauro-OCA: OCA + Linerixibat Arm | 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 tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented. |
| Part A- Tmax for Tauro-OCA: OCA Arm | 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 tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- AUC(0-t) for Glyco-OCA: OCA Arm | 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 glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- AUC(0-24) for Glyco-OCA: OCA Arm | 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 glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Cmax for Glyco-OCA: OCA Arm | 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 glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Average Ctrough for Glyco-OCA: OCA Arm | 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 glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented. |
| Part A- Average Ctrough for Glyco-OCA: OCA + Linerixibat Arm | 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 glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented. |
| Part A- Tmax for Glyco-OCA: OCA Arm | 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 glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of glyco-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part B- Tmax for Total-OCA: OCA Arm | 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- 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of total-OCA. |
| Part B- AUC(0-t) for OCA: OCA Arm | 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 OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| Part B- AUC(0-24) for OCA: OCA Arm | 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 OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA. |
| Part B- AUC(0-t) for Tauro-OCA: OCA Arm | 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 tauro-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA. |
| Part B- AUC(0-24) for Tauro-OCA: OCA Arm | 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 tauro-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA. |
| Part B- Cmax for Tauro-OCA: OCA Arm | 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 tauro-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA. |
| Part B- Ctrough for Tauro-OCA: OCA Arm | 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 tauro-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA. |
| Part B- Tmax for Tauro-OCA: OCA Arm | 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 tauro-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tauro-OCA. |
| Part B- AUC(0-t) for Glyco-OCA: OCA Arm | 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 glyco-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA. |
| Part B- AUC(0-24) for Glyco-OCA: OCA Arm | 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 glyco-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA. |
| Part B- Cmax for Glyco-OCA: OCA Arm | 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 glyco-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA. |
| Part B- Ctrough for Glyco-OCA: OCA Arm | 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 glyco-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA. |
| Part B- Tmax for Glyco-OCA: OCA Arm | 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 glyco-OCA. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of glyco-OCA. |
| Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 52 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. All Participants Population consisted of all participants who took at least 1 dose of study intervention. |
| Part B- Number of Participants With Any AEs and SAEs | Up to Day 52 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. |
| Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected Using Bazzet's Formula (QTcB), Corrected QT Interval Using Fredericia's Formula (QTcF): OCA Arm | Baseline (Day -1), and at Day 17 | Twelve lead electrocardiograms (ECGs) were obtained to measure PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 5 minutes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm | Baseline (Day -1), and at Day 38 | Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 5 minutes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part B- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF | Baseline (Day -1), and up to Day 38 | Twelve lead ECGs were planned to be measured PR interval, QRS duration, QT interval, QTcB and QTcF. Twelve-lead ECGs were planned to be performed with the participant in a supine position after a rest of at least 5 minutes. |
| Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm | Baseline (Day -1), Days 1 and 17 | SBP and DBP were measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | SBP and DBP were measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Pulse Rate: OCA Arm | Baseline (Day -1), Days 1 and 17 | Pulse rate was measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Pulse Rate: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Pulse rate was measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Respiratory Rate: OCA Arm | Baseline (Day -1), Days 1 and 17 | Respiratory rate was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Respiratory Rate: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Respiratory rate was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Body Temperature: OCA Arm | Baseline (Day -1), Days 1 and 17 | Body temperature was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Body Temperature: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Body temperature was measured in supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part B- Change From Baseline in SBP and DBP | Baseline (Day -1), and up to Day 38 | SBP and DBP were planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. |
| Part B- Change From Baseline in Pulse Rate | Baseline (Day -1), and up to Day 38 | Pulse rate was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. |
| Part B- Change From Baseline in Respiratory Rate | Baseline (Day -1), and up to Day 38 | Respiratory rate was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. |
| Part B- Change From Baseline in Body Temperature | Baseline (Day -1), and up to Day 38 | Body temperature was planned to be measured in a supine position after 5 minutes of rest for the participants in a quiet setting without distractions. |
| Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the hematology parameters: erythrocytes and reticulocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the hematology parameters: erythrocytes and reticulocytes. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part B- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and leukocytes. |
| Part B- Change From Baseline in Hematology Parameter: Hemoglobin | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the hematology parameter: hemoglobin. |
| Part B- Change From Baseline in Hematology Parameter: Hematocrit | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the hematology parameter: hematocrit. |
| Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. |
| Part B- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. |
| Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameter: Protein: OCA Arm | Baseline (Day -1) and at Day 17 | Blood samples were collected to analyze the chemistry parameter: protein. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part A- Change From Baseline in Chemistry Parameter: Protein: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Blood samples were collected to analyze the chemistry parameter: protein. Baseline was considered as Day -1. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Part B- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the chemistry parameters: glucose, calcium, potassium, sodium and urea. |
| Part B- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. |
| Part B- Change From Baseline in Chemistry Parameters: ALT, ALP, AST | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the chemistry parameters: ALT, ALP and AST. |
| Part B- Change From Baseline in Chemistry Parameter: Protein | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the chemistry parameter: protein. |
| Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Baseline (Day -1) and at Day 17 | Urine samples were collected from participants for urinalysis for measuring potential of hydrogen (pH) and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes and were counted as cells per high-power field (cells/HPF). Baseline was considered as Day -1. Number of participants with worst case urinalysis result by microscopic examination have been presented. |
| Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Baseline (Day -1) and at Day 38 | Urine samples were collected from participants for urinalysis for measuring pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes and were counted as cells/HPF. Baseline was considered as Day -1. Number of participants with worst case urinalysis result by microscopic examination have been presented. |
| Part B- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline | Baseline (Day -1), and up to Day 38 | Urine samples were planned to be collected from participants for urinalysis for measuring pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Abnormal urinalysis was planned to be sent for microscopic examination for cellular casts, erythrocytes, granular casts, hyaline casts, and leukocytes. |
| Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods. |
| Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods. |
| Part A- Cmax for Linerixibat: OCA + Linerixibat Arm | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods. |
| Part A- Tmax for Linerixibat: OCA + Linerixibat Arm | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of linerixibat. Pharmacokinetic parameters were analyzed using standard non-compartmental methods. |
| Part B- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm | 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat. |
| Part B- AUC(0-12) for Linerixibat: OCA + Linerixibat Arm | 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat. |
| Part B- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes | Baseline (Day -1), and up to Day 38 | Blood samples were planned to be collected to analyze the hematology parameters: erythrocytes and reticulocytes. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat. |
| 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 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Tmax for Total-OCA: OCA + Linerixibat Arm | 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- 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of total-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- AUC(0-t) for OCA: OCA Arm | 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 OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- AUC(0-24) for OCA: OCA Arm | 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 OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Cmax for OCA: OCA Arm | 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 OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- Average Ctrough for OCA: OCA Arm | 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 OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 17, 18 and 19 has been presented. |
| Part A- Average Ctrough for OCA: OCA + Linerixibat Arm | 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 OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Average of Ctrough measurement from study Days 35, 36, 37 and 38 has been presented. |
| Part A- Tmax for OCA: OCA Arm | 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 OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis of OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
| Part A- AUC(0-t) for Tauro-OCA: OCA Arm | 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 tauro-OCA. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. |
Countries
United Kingdom
Participant flow
Recruitment details
This was an open-label, drug interaction study to investigate the effect of linerixibat on plasma concentrations of obeticholic acid (OCA) and OCA conjugates in healthy participants. The study was conducted at a single center in the United Kingdom.
Pre-assignment details
A total of 19 participants were enrolled in Part A. Part B was optional and since there was no clinical benefit seen in conducting Part B of this study, no participants were enrolled in Part B. The study was concluded following completion of Part A.
Participants by arm
| Arm | Count |
|---|---|
| Part A: OCA 10 mg Followed by OCA 10 mg + Linerixibat 90 mg In Period 1, participants received OCA 10 milligram (mg), tablets, orally, once daily (afternoon dose) for 19 days (study Day 1 to Day 19). In Period 2 participants were administered OCA 10 mg, tablets, orally, once daily (afternoon dose) for 18 days (study Day 20 to Day 37) along with linerixibat 90 mg, tablets, orally, twice daily for 18.5 days (study Day 20 to the morning of Day 38). There was no washout period between Period 1 and Period 2. | 19 |
| Part B: OCA 5mg or 10mg Followed by OCA 10mg+Linerixibat 180mg In Part B, participants were planned to receive OCA 5 mg or 10 mg, tablets, orally, once daily (evening dose) for 19 days (study Day 1 to Day 19) in Period 1; followed by OCA 10 mg, tablets, orally, once daily (evening dose) for 18 days (study Day 20 to Day 37) along with linerixibat 180 mg, tablets, orally, once daily for 18.5 days (study Day 20 to the morning of Day 38) in Period 2. There was no planned washout period between Period 1 and Period 2. | 0 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A: Period 2 (Day 20 to Day 38) | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: OCA 10 mg Followed by OCA 10 mg + Linerixibat 90 mg |
|---|---|---|
| Age, Continuous | 44.9 Years STANDARD_DEVIATION 10.28 | 44.9 Years STANDARD_DEVIATION 10.28 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 18 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 10 / 19 | 14 / 19 |
| serious Total, serious adverse events | 0 / 19 | 1 / 19 |
Outcome results
Primary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | 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 | 2349.552 Hours*nanogram per milliliter | Geometric Coefficient of Variation 43.55 |
Primary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | 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 | 2329.804 Hours*nanogram per milliliter | Geometric Coefficient of Variation 43.54 |
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for Total-OCA at Steady State: OCA + Linerixibat Arm | 787.007 Hours*nanogram per milliliter | Geometric Coefficient of Variation 55.17 |
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for Total-OCA at Steady State: OCA + Linerixibat Arm | 782.528 Hours*nanogram per milliliter | Geometric Coefficient of Variation 55.81 |
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for Total-OCA at Steady State: OCA + Linerixibat Arm | 21.680 Nanogram per milliliter | Geometric Coefficient of Variation 85.11 |
Primary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Trough Concentration (Ctrough) for Total-OCA at Steady State: OCA Arm | 85.312 Nanogram per milliliter | Geometric Coefficient of Variation 53.13 |
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for Total-OCA at Steady State: OCA + Linerixibat Arm | 83.403 Nanogram per milliliter | Geometric Coefficient of Variation 45.55 |
Primary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Maximum Observed Concentration (Cmax) for Total-OCA at Steady State: OCA Arm | 206.409 Nanogram per milliliter | Geometric Coefficient of Variation 41.18 |
Primary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Primary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm | Day 20, n=13 | 322.580 Hours*picogram per milliliter | Geometric Coefficient of Variation 121.05 |
| Part A: OCA 10 mg | Part A- Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) for Linerixibat: OCA + Linerixibat Arm | Day 33, n=17 | 1071.982 Hours*picogram per milliliter | Geometric Coefficient of Variation 144.57 |
Secondary
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.
Time frame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 hours and 24 hours (Day 19) post-dose
Population: PK Parameters Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm | Day 17 | 92.1116 Nanogram per milliliter | Standard Deviation 57.86113 |
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm | Day 18 | 95.1600 Nanogram per milliliter | Standard Deviation 57.50955 |
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA Arm | Day 19 | 102.5168 Nanogram per milliliter | Standard Deviation 66.65649 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 hours and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm | Day 35 | 30.8972 Nanogram per milliliter | Standard Deviation 25.55139 |
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm | Day 36 | 28.8489 Nanogram per milliliter | Standard Deviation 27.08479 |
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm | Day 37 | 26.4411 Nanogram per milliliter | Standard Deviation 21.63264 |
| Part A: OCA 10 mg | Part A- Assessment of Steady State Using Ctrough of Total-OCA: OCA + Linerixibat Arm | Day 38 | 27.8644 Nanogram per milliliter | Standard Deviation 21.08848 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for Glyco-OCA: OCA Arm | 1757.140 Hours*nanogram per milliliter | Geometric Coefficient of Variation 44.1 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for Glyco-OCA: OCA + Linerixibat Arm | 654.629 Hours*nanogram per milliliter | Geometric Coefficient of Variation 57.45 |
Secondary
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.
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
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for OCA: OCA Arm | 163.701 Hours*nanogram per milliliter | Geometric Coefficient of Variation 59.51 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for OCA: OCA + Linerixibat Arm | 130.092 Hours * nanogram per milliliter | Geometric Coefficient of Variation 53.8 |
Secondary
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.
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
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for Tauro-OCA: OCA Arm | 744.365 Hours*nanogram per milliliter | Geometric Coefficient of Variation 68.92 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-24) for Tauro-OCA: OCA + Linerixibat Arm | 89.946 Hours*nanogram per milliliter | Geometric Coefficient of Variation 64.5 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for Glyco-OCA: OCA Arm | 1741.969 Hours*nanogram per milliliter | Geometric Coefficient of Variation 44.11 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for Glyco-OCA: OCA + Linerixibat Arm | 650.683 Hours*nanogram per milliliter | Geometric Coefficient of Variation 58.17 |
Secondary
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.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm | Day 20, n=16 | 230.609 Hours*picogram per milliliter | Geometric Coefficient of Variation 153.14 |
| Part A: OCA 10 mg | Part A- AUC(0-t) for Linerixibat: OCA + Linerixibat Arm | Day 33, n=19 | 903.881 Hours*picogram per milliliter | Geometric Coefficient of Variation 142.27 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for OCA: OCA Arm | 158.337 Hours*nanogram per milliliter | Geometric Coefficient of Variation 59.45 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for OCA: OCA + Linerixibat Arm | 127.171 Hours*nanogram per milliliter | Geometric Coefficient of Variation 53.12 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for Tauro-OCA: OCA Arm | 712.567 Hours*nanogram per milliliter | Geometric Coefficient of Variation 61.28 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- AUC(0-t) for Tauro-OCA: OCA + Linerixibat Arm | 89.486 Hours*nanogram per milliliter | Geometric Coefficient of Variation 64.85 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for Glyco-OCA: OCA Arm | 66.043 Nanogram per milliliter | Geometric Coefficient of Variation 50.72 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for Glyco-OCA: OCA + Linerixibat Arm | 19.498 Nanogram per milliliter | Geometric Coefficient of Variation 85.88 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for OCA: OCA Arm | 2.609 Nanogram per milliliter | Geometric Coefficient of Variation 69.77 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for OCA: OCA + Linerixibat Arm | 2.060 Nanogram per milliliter | Geometric Coefficient of Variation 83.57 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for Tauro-OCA: OCA Arm | 28.014 Nanogram per milliliter | Geometric Coefficient of Variation 76.45 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Average Ctrough for Tauro-OCA: OCA + Linerixibat Arm | 2.600 Nanogram per milliliter | Geometric Coefficient of Variation 124.06 |
Secondary
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.
Time frame: Baseline (Day -1), Days 1 and 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Body Temperature: OCA Arm | Day 1 | 0.15 Degrees Celsius | Standard Deviation 0.356 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Body Temperature: OCA Arm | Day 17 | 0.05 Degrees Celsius | Standard Deviation 0.336 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Body Temperature: OCA + Linerixibat Arm | 0.09 Degrees Celsius | Standard Deviation 0.327 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameter: Protein: OCA Arm | 1.5 Grams per liter | Standard Deviation 3.13 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameter: Protein: OCA + Linerixibat Arm | 0.7 Grams per liter | Standard Deviation 2.66 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm | ALP | 0.6 International units per liter | Standard Deviation 5.5 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm | ALT | -2.7 International units per liter | Standard Deviation 4.75 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST): OCA Arm | AST | -2.2 International units per liter | Standard Deviation 3.03 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm | ALT, n=17 | 9.4 International units per liter | Standard Deviation 38.04 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm | ALP, n=18 | 0.0 International units per liter | Standard Deviation 9.49 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: ALT, ALP, AST: OCA + Linerixibat Arm | AST, n=16 | -0.9 International units per liter | Standard Deviation 8.5 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm | Bilirubin | 0.1 Micromoles per liter | Standard Deviation 2.42 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm | Creatinine | -2.2 Micromoles per liter | Standard Deviation 7.71 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA Arm | Direct Bilirubin | 0.0001 Micromoles per liter | Standard Deviation 0.88192 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm | Creatinine, n=18 | 5.4 Micromoles per liter | Standard Deviation 6.83 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm | Bilirubin, n=18 | 1.1 Micromoles per liter | Standard Deviation 2.72 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin: OCA + Linerixibat Arm | Direct Bilirubin, n=16 | 0.3126 Micromoles per liter | Standard Deviation 0.79317 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm | Glucose | -0.09 Millimoles per liter | Standard Deviation 0.537 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm | Calcium | 0.041 Millimoles per liter | Standard Deviation 0.0891 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm | Potassium | -0.02 Millimoles per liter | Standard Deviation 0.429 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm | Sodium | -0.2 Millimoles per liter | Standard Deviation 2.1 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA Arm | Urea | -0.0395 Millimoles per liter | Standard Deviation 0.32717 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm | Glucose, n=18 | -0.44 Millimoles per liter | Standard Deviation 0.343 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm | Calcium, n=18 | -0.001 Millimoles per liter | Standard Deviation 0.0506 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm | Potassium, n=16 | 0.10 Millimoles per liter | Standard Deviation 0.493 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm | Sodium, n=18 | -0.9 Millimoles per liter | Standard Deviation 1.89 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea: OCA + Linerixibat Arm | Urea, n=18 | -0.1507 Millimoles per liter | Standard Deviation 0.24902 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA Arm | -0.01 Picograms | Standard Deviation 0.624 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin: OCA + Linerixibat Arm | -0.13 Picograms | Standard Deviation 0.552 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA Arm | -0.37 Femtoliter | Standard Deviation 1.797 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume: OCA + Linerixibat Arm | -1.03 Femtoliter | Standard Deviation 1.972 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA Arm | -0.0003 Proportion of red blood cells in blood | Standard Deviation 0.01614 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Hematocrit: OCA + Linerixibat Arm | -0.0054 Proportion of red blood cells in blood | Standard Deviation 0.01857 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA Arm | 0.4 Grams per liter | Standard Deviation 6.33 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameter: Hemoglobin: OCA + Linerixibat Arm | -0.8 Grams per liter | Standard Deviation 5.09 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Basophils | -0.002 10^9 cells per liter | Standard Deviation 0.0144 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Eosinophils | -0.013 10^9 cells per liter | Standard Deviation 0.0549 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Lymphocytes | -0.091 10^9 cells per liter | Standard Deviation 0.4444 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Monocytes | 0.033 10^9 cells per liter | Standard Deviation 0.1125 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Neutrophils | 0.064 10^9 cells per liter | Standard Deviation 0.8205 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Platelet count | 4.3 10^9 cells per liter | Standard Deviation 22.85 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA Arm | Leukocytes | -0.011 10^9 cells per liter | Standard Deviation 0.776 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Basophils | 0.000 10^9 cells per liter | Standard Deviation 0.0091 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Eosinophils | 0.029 10^9 cells per liter | Standard Deviation 0.0801 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Lymphocytes | 0.169 10^9 cells per liter | Standard Deviation 0.3534 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Monocytes | 0.047 10^9 cells per liter | Standard Deviation 0.0932 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Neutrophils | 0.278 10^9 cells per liter | Standard Deviation 1.2073 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Platelet count | -4.1 10^9 cells per liter | Standard Deviation 20.77 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, Leukocytes: OCA + Linerixibat Arm | Leukocytes | 0.524 10^9 cells per liter | Standard Deviation 1.1981 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm | Erythrocytes | 0.021 10^12 cells per liter | Standard Deviation 0.1919 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA Arm | Reticulocytes | -0.0004 10^12 cells per liter | Standard Deviation 0.01165 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm | Erythrocytes | 0.002 10^12 cells per liter | Standard Deviation 0.234 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes: OCA + Linerixibat Arm | Reticulocytes | 0.0074 10^12 cells per liter | Standard Deviation 0.0165 |
Secondary
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.
Time frame: Baseline (Day -1), and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm | PR Interval | 2.5 Millisecond | Standard Deviation 12.96 |
| Part A: OCA 10 mg | Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm | QRS Duration | -2.3 Millisecond | Standard Deviation 2.97 |
| Part A: OCA 10 mg | Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm | QT Interval | -2.7 Millisecond | Standard Deviation 13.05 |
| Part A: OCA 10 mg | Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm | QTcB Interval | -2.9 Millisecond | Standard Deviation 13.18 |
| Part A: OCA 10 mg | Part A- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcB, QTcF: OCA + Linerixibat Arm | QTcF Interval | -2.9 Millisecond | Standard Deviation 9.58 |
Secondary
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.
Time frame: Baseline (Day -1), and at Day 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | 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 | PR Interval | -3.7 Millisecond | Standard Deviation 8.27 |
| Part A: OCA 10 mg | 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 | QRS Duration | -1.2 Millisecond | Standard Deviation 4.66 |
| Part A: OCA 10 mg | 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 | QT Interval | -3.4 Millisecond | Standard Deviation 14.56 |
| Part A: OCA 10 mg | 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 | QTcB Interval | 4.2 Millisecond | Standard Deviation 13.31 |
| Part A: OCA 10 mg | 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 | QTcF Interval | 1.6 Millisecond | Standard Deviation 10.43 |
Secondary
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.
Time frame: Baseline (Day -1), Days 1 and 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Pulse Rate: OCA Arm | Day 1 | 7.2 Beats per minute | Standard Deviation 6.54 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Pulse Rate: OCA Arm | Day 17 | 1.8 Beats per minute | Standard Deviation 7.45 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Pulse Rate: OCA + Linerixibat Arm | -0.3 Beats per minute | Standard Deviation 8.96 |
Secondary
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.
Time frame: Baseline (Day -1), Days 1 and 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Respiratory Rate: OCA Arm | Day 1 | 0.2 Breaths per minute | Standard Deviation 1.95 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Respiratory Rate: OCA Arm | Day 17 | 0.4 Breaths per minute | Standard Deviation 1.77 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Respiratory Rate: OCA + Linerixibat Arm | 0.4 Breaths per minute | Standard Deviation 2.09 |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm | SBP | -0.7 Millimeters of mercury | Standard Deviation 8.48 |
| Part A: OCA 10 mg | Part A- Change From Baseline in SBP and DBP: OCA + Linerixibat Arm | DBP | 0.8 Millimeters of mercury | Standard Deviation 2.98 |
Secondary
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.
Time frame: Baseline (Day -1), Days 1 and 17
Population: All Participants Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm | SBP: Day 1 | -0.9 Millimeters of mercury | Standard Deviation 6.83 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm | SBP: Day 17 | 0.5 Millimeters of mercury | Standard Deviation 5.94 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm | DBP: Day 1 | -4.5 Millimeters of mercury | Standard Deviation 4.17 |
| Part A: OCA 10 mg | Part A- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): OCA Arm | DBP: Day 17 | 0.1 Millimeters of mercury | Standard Deviation 3.96 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for Glyco-OCA: OCA Arm | 141.770 Nanogram per milliliter | Geometric Coefficient of Variation 39.46 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for Glyco-OCA: OCA + Linerixibat Arm | 65.633 Nanogram per milliliter | Geometric Coefficient of Variation 50.27 |
Secondary
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.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for Linerixibat: OCA + Linerixibat Arm | Day 20, n=17 | 56.927 Picogram per milliliter | Geometric Coefficient of Variation 173.55 |
| Part A: OCA 10 mg | Part A- Cmax for Linerixibat: OCA + Linerixibat Arm | Day 33, n=19 | 163.624 Picogram per milliliter | Geometric Coefficient of Variation 123.48 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for OCA: OCA Arm | 50.820 Nanogram per milliliter | Geometric Coefficient of Variation 71.94 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for OCA: OCA + Linerixibat Arm | 35.495 Nanogram per milliliter | Geometric Coefficient of Variation 61.88 |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for Tauro-OCA: OCA Arm | 62.347 Nanogram per milliliter | Geometric Coefficient of Variation 60.84 |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Cmax for Tauro-OCA: OCA + Linerixibat Arm | 10.224 Nanogram per milliliter | Geometric Coefficient of Variation 61.53 |
Secondary
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.
Time frame: Up to Day 52
Population: All Participants Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 10 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Part A: OCA 10 mg + Linerixibat 90 mg | Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 14 Participants |
| Part A: OCA 10 mg + Linerixibat 90 mg | Part A- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 1 Participants |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 17
Population: All Participants Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Cellular casts: No change | 5 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Cellular casts: Increase to 1-9/HPF | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Erythrocytes: No change | 4 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Erythrocytes: Increase to 1-9/HPF | 1 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Granular casts: No change | 5 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Granular casts: Increase to 1-9/HPF | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Hyaline casts: No change | 5 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Hyaline casts: Increase to 1-9/HPF | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Leukocytes: No change | 4 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA Arm | Leukocytes: Increase to 1-9/HPF | 1 Participants |
Secondary
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.
Time frame: Baseline (Day -1) and at Day 38
Population: All Participants Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Cellular casts: No change | 1 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Cellular casts: Increase to 1-9/HPF | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Erythrocytes: No change | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Erythrocytes: Increase to 1-9/HPF | 1 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Granular casts: No change | 1 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Granular casts: Increase to 1-9/HPF | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Hyaline casts: No change | 1 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Hyaline casts: Increase to 1-9/HPF | 0 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Leukocytes: No change | 1 Participants |
| Part A: OCA 10 mg | Part A- Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline: OCA + Linerixibat Arm | Leukocytes: Increase to 1-9/HPF | 0 Participants |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total-OCA: OCA Arm | 1.00 Hours |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for Glyco-OCA: OCA Arm | 2.00 Hours |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for Glyco-OCA: OCA + Linerixibat Arm | 5.00 Hours |
Secondary
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.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for Linerixibat: OCA + Linerixibat Arm | Day 20, n=17 | 3.92 Hours |
| Part A: OCA 10 mg | Part A- Tmax for Linerixibat: OCA + Linerixibat Arm | Day 33, n=19 | 5.00 Hours |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for OCA: OCA Arm | 0.75 Hours |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for OCA: OCA + Linerixibat Arm | 0.88 Hours |
Secondary
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.
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
Population: PK Parameters Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for Tauro-OCA: OCA Arm | 2.00 Hours |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for Tauro-OCA: OCA + Linerixibat Arm | 5.00 Hours |
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: OCA 10 mg | Part A- Tmax for Total-OCA: OCA + Linerixibat Arm | 3.00 Hours |
Secondary
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.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Change From Baseline in Chemistry Parameter: Protein
Blood samples were planned to be collected to analyze the chemistry parameter: protein.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were planned to be collected to analyze the hematology parameter: hematocrit.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were planned to be collected to analyze the hematology parameter: hemoglobin.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Cmax for Linerixibat: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Cmax for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time frame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Cmax for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Ctrough for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time frame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Ctrough for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Up to Day 52
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Baseline (Day -1), and up to Day 38
Population: All Participants Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Tmax for Linerixibat: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of linerixibat.
Time frame: Days 20 and 33: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Tmax for OCA: OCA Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time frame: Day 17: Pre-dose; Day 18: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 19) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B- Tmax for OCA: OCA + Linerixibat Arm
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of OCA.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
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
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.
Secondary
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.
Time frame: Days 35 and 36: Pre-dose; Day 37: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours (Day 38) post-dose
Population: PK Parameters Population. Data was not collected as no participants were enrolled in Part B.