Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat

A Two-period Study in Healthy Male Participants to Determine the Pharmacokinetics, Balance/Excretion, and Metabolism of [14C]-Linerixibat Following a Single Intravenous Radiolabeled Microtracer Dose (Concomitant With a Non-radiolabeled Oral Dose) and a Single Oral Radiolabeled Dose

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03992014

Enrollment

Registered

2019-06-19

Start date

2019-07-08

Completion date

2019-08-26

Last updated

2020-06-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cholestasis

Keywords

[14C]-linerixibat, GSK2330672, Microtracer dose

Brief summary

Absorption, metabolism and excretion of linerixibat have been studied in previous clinical trials. However, no dedicated clinical studies of drug absorption, metabolism, and excretion have been conducted for linerixibat. The purpose of this study is to determine the PK, balance/excretion, and metabolism of radiolabeled 14 Carbon \[14C\]-linerixibat following a single intravenous (IV) radiolabeled microtracer dose (concomitant with a non-radiolabeled oral dose) and a single oral radiolabeled dose. This is a single group, two period, single sequence, and mass balance study will enroll 6 healthy male subjects. Each subject will be involved in the study for up to 10 weeks which includes screening period, two treatment periods (treatment Periods 1 and 2), separated by about 7 days (at least 13 days between oral doses), and a follow-up visit 1-2 weeks after the last assessment in treatment Period 2.

Interventions

DRUGLinerixibat tablet

Linerixibat will be available as white to slightly colored film-coated round tablet to be administered as two tablets taken in the fasted state in the morning with 240 milliliter (mL) of room temperature water.

DRUG[14C]-linerixibat intravenous infusion

\[14C\]-linerixibat will be available as clear, colorless solution free from visible particulates to be administered 25 mL IV over 3 hours immediately after the oral dose.

DRUGLinerixibat oral solution

Linerixibat will be available as clear, colorless solution free from visible particulates to be administered 60 mL solution in the fasted state in the morning.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

This will be an open-label study. Hence, there will be no masking.

Intervention model description

Subjects will receive linerixibat tablets concomitantly with \[14C\]-linerixibat IV infusion in treatment Period 1 and \[14C\]-linerixibat oral solution in treatment Period 2.

Eligibility

Sex/Gender

MALE

Age

30 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Aged 30 to 55 years, 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 subject 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 and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * History of regular bowel movements (averaging one or more bowel movements per day). * Non-smoker, or ex-smoker who hasn't regularly smoked for the 6 months before screening. * Body weight of 50 kilogram and above, and body mass index (BMI) within the range 19.0 to 31.0 kilogram per square meter (kg/m\^2) (inclusive). * Male only. Subjects must agree to use contraception as follows: subjects with female partners of childbearing potential must agree to use a condom from the time of first dose of study intervention until 1 month after their last dose. * Capable of giving signed informed consent.

Exclusion criteria

* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Subjects with a history of cholecystectomy must be excluded. * 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, or chronic history of diarrhoea. * Lymphoma, leukemia, 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 (example given \[e.g.\], psychiatric disorder, senility, dementia, or other condition), clinical or laboratory abnormality, or examination finding that the investigator considers would put the subjects 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 \>21 units. One unit is equivalent to 8 gram of alcohol: a glass (approximately 240 mL) of beer, 1 small glass (approximately 100 mL) of wine or 1 (approximately 25 mL) measure of spirits. * History of or regular use of tobacco- or nicotine-containing products in the 6 months prior to screening. * Past or intended use of over-the-counter or prescription medication, including analgesics (e.g., paracetamol), herbal medications, or grapefruit and Seville orange juices within 14 days prior to the first dose of study intervention until completion of the follow-up visit. * Administration of any other Ileal bile acid transporter (IBAT) inhibitor in the 3 months prior to screening. * Current enrolment in a clinical trial; recent participation in a clinical trial and has received an investigational product within 3 months 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. * Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A subjects previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study. * Received a total body radiation dose of greater than 10.0 millisievert (upper limit of International Commission on Radiological Protection \[IRCP\] category II) or exposure to significant radiation (e.g., serial x-ray or computed tomography \[CT\] scans, barium meal, etc.) in the 3 years before this study. * Alanine transaminase (ALT) \>1.5\* upper limit of normal (ULN). * Bilirubin \>1.5\*ULN (isolated bilirubin \>1.5\*ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]). * Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study intervention. * Screening estimated glomerular filtration rate (eGFR) \<45 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2) based on the Modification of Diet in Renal Disease (MDRD) Study equation. * Positive pre-study drug/alcohol screen. * Urinary cotinine levels indicative of smoking. * Positive human immunodeficiency virus (HIV) antibody test. * QT duration corrected for heart rate by Fridericia's formula \>450 millisecond on ECG performed at Screening * At screening or prior to the first dose, a supine blood pressure that is persistently higher than 140/90 millimeters of mercury (mmHg) taken in triplicate, unless deemed not clinically significant by the investigator. * At screening or prior to the first dose, a supine mean heart rate outside the range of 40-100 beats per minute, unless deemed not clinically significant by the investigator. * Has had an occupation which requires monitoring for radiation exposure, nuclear medicine procedures, or excessive x-rays within the past 12 months. * Unable to refrain from consumption of prohibited food and drinks from 7 days before the first dose of study medication until the follow up visit. * Loss of more than 400 mL blood during the 3 months before screening, e.g. as a blood donor, or plan to donate blood or blood products in the 3 months after the end of the trial. * Unwillingness or inability to follow the procedures outlines in the protocol, including the use of the string bile collection device. * History of sensitivity to linerixibat, or their components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.

Design outcomes

Primary

Measure	Time frame	Description
Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose	Feces samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.
Period 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates geometric coefficient of variation could not be calculated as a single participant was analyzed.
Period 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Hepatic clearance was calculated as total plasma IV clearance minus renal clearance.
Period 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. It is expressed as percentage bioavailability, which is calculated by ratio of AUC(oral)/Dose(oral) with AUC(IV)/Dose(IV) multiplied by 100.
Period 1: Percentage of Drug Escaping First-pass Hepatic Clearance (Fh) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected from participants at indicated time points. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).
Period 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected from participants at indicated time points. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100.
Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose	Urine samples were collected at indicated time points and total radioactivity measurement was done using Liquid Scintillation counting (LSC). Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.
Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose	Urine samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.
Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose	Feces samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.
Period 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Secondary

Measure	Time frame	Description
Number of Participants With Worst Case Hematology Results Relative to Normal Range	Up to 34 days	Blood samples were collected to analyze the following hematology parameters; Basophils, Eosinophils, Erythrocytes mean corpuscular volume (MCV), Erythrocytes mean corpuscular hemoglobin (MCH), Erythrocytes, Hematocrit (HCT), Hemoglobin (Hb), Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes and Reticulocytes/Erythrocytes. Participants were counted in the worst case category if their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Up to 34 days	Blood samples were collected to analyze the following clinical chemistry parameters; alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, calcium, chloride, cholesterol, creatinine, direct bilirubin, globulin, glucose, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, phosphate, potassium, protein, sodium, triglycerides, urate and urea. Participants were counted in the worst case category if their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Number of Participants With Abnormal Urinalysis Results by Dipstick Method	Up to 34 days	Urine samples were collected to assess urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine urobilinogen, urine nitrite and urine leukocyte esterase by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter can be read as negative (-) and positive (+) indicating proportional concentrations in the urine sample. Number of participants who had abnormal findings in any of these urinalysis parameters are presented.
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters	Up to 34 days	Full 12-lead ECGs were recorded with the participants in a supine position. 12-lead ECGs were obtained using an automated ECG machine that measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals and calculated heart rate. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with clinically significant abnormal findings for ECG parameters at worst-case post Baseline are presented.
Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	DBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Period 2: Change From Baseline in DBP at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	DBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Change From Baseline in DBP at Follow-up Visit (Day 34)	Baseline and Day 34 (post Day 1 of Period 1 dosing)	DBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Period 1: Change From Baseline in Pulse Rate at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	Pulse rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Period 2: Change From Baseline in Pulse Rate at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	Pulse rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)	Baseline and Day 34 (post Day 1 of Period 1 dosing)	Pulse rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	SBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Period 2: Change From Baseline in SBP at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	SBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Change From Baseline in SBP at Follow-up Visit (Day 34)	Baseline and Day 34 (post Day 1 of Period 1 dosing)	SBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	Respiratory rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	Respiratory rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)	Baseline and Day 34 (post Day 1 of Period 1 dosing)	Respiratory rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	Tympanic membrane temperature was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points	Baseline, Day 1 (4 Hours) and Day 8	Tympanic membrane temperature was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)	Baseline and Day 34 (post Day 1 of Period 1 dosing)	Tympanic membrane temperature was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 34 days	AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study treatment. An SAE is 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.

Countries

United Kingdom

Participant flow

Recruitment details

This was a two-period, mass balance study in healthy male participants to assess the pharmacokinetics (PK), excretion and metabolism of Linerixibat. The study was conducted at a single center in the United Kingdom.

Pre-assignment details

A total of 10 participants were screened of which 4 failed screening and 6 participants were enrolled in the study. The study had 2 treatment periods (each of 8 days) with a washout of 7 days. All participants were followed-up at Day 34.

Participants by arm

Arm	Count
Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol Participants were administered a single oral dose of 90 milligram (mg) linerixibat (two tablets \[tab\] of 45 mg each) in fasted state followed by an intravenous (IV) infusion of 100 micrograms (μg) radiolabeled \[14C\]-linerixibat infused over 3 hours on Day 1 of treatment period 1. Participants received 60 milliliter (mL) of 90 mg \[14C\]-linerixibat oral solution (sol) in the fasted state on Day 1 of treatment period 2. The treatment periods were separated by a washout period of about 7 days (at least 13 days between oral doses). All participants were followed-up at Day 34.	6
Total	6

Arm

Count

Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol

Participants were administered a single oral dose of 90 milligram (mg) linerixibat (two tablets \[tab\] of 45 mg each) in fasted state followed by an intravenous (IV) infusion of 100 micrograms (μg) radiolabeled \[14C\]-linerixibat infused over 3 hours on Day 1 of treatment period 1. Participants received 60 milliliter (mL) of 90 mg \[14C\]-linerixibat oral solution (sol) in the fasted state on Day 1 of treatment period 2. The treatment periods were separated by a washout period of about 7 days (at least 13 days between oral doses). All participants were followed-up at Day 34.

Total

Baseline characteristics

Characteristic	Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Age, Continuous	41.2 Years STANDARD_DEVIATION 8.13
Race/Ethnicity, Customized Black or African American	2 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	4 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 6
other Total, other adverse events	3 / 6	3 / 6
serious Total, serious adverse events	0 / 6	0 / 6

Outcome results

Primary

Period 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. It is expressed as percentage bioavailability, which is calculated by ratio of AUC(oral)/Dose(oral) with AUC(IV)/Dose(IV) multiplied by 100.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	0.0517 Percentage bioavailability	Geometric Coefficient of Variation 120

Primary

Period 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population comprised of all participants in the Safety Population (all participants who took atleast one dose of study treatment) who had at least 1 non-missing PK assessment. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Linerixibat 90 mg oral tablets	1554 Hours*picogram per milliliter	Geometric Coefficient of Variation 25.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	[14C] Linerixibat 100 μg IV	1570 Hours*picogram per milliliter	Geometric Coefficient of Variation 26.7

Primary

Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates geometric coefficient of variation could not be calculated as a single participant was analyzed.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat	2300 Hours*picogram equivalent per milliliter

Primary

Period 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat	1903 Hours*picogram equivalent per milliliter	Geometric Coefficient of Variation 22.3

Primary

Period 1: AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Linerixibat 90 mg oral tablets	749 Hours*picogram per milliliter	Geometric Coefficient of Variation 125
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	[14C] Linerixibat 100 μg IV	1560 Hours*picogram per milliliter	Geometric Coefficient of Variation 26.8

Primary

Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat	738 Picogram equivalent per milliliter	Geometric Coefficient of Variation 23.6

Primary

Period 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Hepatic clearance was calculated as total plasma IV clearance minus renal clearance.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat	867 Milliliters per minute	Geometric Coefficient of Variation 26.4

Primary

Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Linerixibat 90 mg oral tablets	120 Picogram per milliliter	Geometric Coefficient of Variation 108
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	[14C] Linerixibat 100 μg IV	638 Picogram per milliliter	Geometric Coefficient of Variation 27.3

Primary

Period 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected from participants at indicated time points. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	0.167 Percentage of drug absorbed	Geometric Coefficient of Variation 73.7

Primary

Period 1: Percentage of Drug Escaping First-pass Hepatic Clearance (Fh) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected from participants at indicated time points. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Percentage of Drug Escaping First-pass Hepatic Clearance (Fh) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	24.4 Percentage of drug escaped	Geometric Coefficient of Variation 68.4

Primary

Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat

Feces samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.

Time frame: 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose

Population: PK Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-48 Hours	43.6 Percentage dose	Standard Deviation 18.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-72 Hours	61.3 Percentage dose	Standard Deviation 7.5
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-96 Hours	67.8 Percentage dose	Standard Deviation 6.3
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-120 Hours	68.8 Percentage dose	Standard Deviation 6.3
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-144 Hours	69.1 Percentage dose	Standard Deviation 6.3
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-168 Hours	69.2 Percentage dose	Standard Deviation 6.3
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat	0-24 Hours	33.4 Percentage dose	Standard Deviation 19.4

Primary

Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.

Urine samples were collected at indicated time points and total radioactivity measurement was done using Liquid Scintillation counting (LSC). Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.

Time frame: 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose

Population: PK Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-24 Hours	16.4 Percentage dose	Standard Deviation 2.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-48 Hours	16.4 Percentage dose	Standard Deviation 2.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-72 Hours	16.5 Percentage dose	Standard Deviation 2.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-96 Hours	16.5 Percentage dose	Standard Deviation 2.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-120 Hours	16.5 Percentage dose	Standard Deviation 2.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-144 Hours	16.5 Percentage dose	Standard Deviation 2.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.	0-168 Hours	16.5 Percentage dose	Standard Deviation 2.8

Primary

Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat	0.733 Hours

Primary

Period 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Linerixibat 90 mg oral tablets	6.76 Hours	Geometric Coefficient of Variation 124
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	[14C] Linerixibat 100 μg IV	0.828 Hours	Geometric Coefficient of Variation 18.3

Primary

Period 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Group	Value (MEDIAN)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	Linerixibat 90 mg oral tablets	2.25 Hours
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat	[14C] Linerixibat 100 μg IV	1.49 Hours

Primary

Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (MEDIAN)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat	1.49 Hours

Primary

Period 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat	1032 Milliliters per minute	Geometric Coefficient of Variation 27.3

Primary

Period 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat	16340 Milliliter	Geometric Coefficient of Variation 35.7

Primary

Period 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution	1634 Hours*picogram per milliliter	Geometric Coefficient of Variation 95.3

Primary

Period 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution	94740 Hours*picogram equivalent per milliliter	Geometric Coefficient of Variation 8.17

Primary

Period 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	1044 Hours*picogram per milliliter	Geometric Coefficient of Variation 79.4

Primary

Period 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	67533 Hours*picogram equivalent per milliliter	Geometric Coefficient of Variation 11.3

Primary

Period 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	158 Picogram per milliliter	Geometric Coefficient of Variation 270

Primary

Period 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	2784 Picogram equivalent per milliliter	Geometric Coefficient of Variation 14.3

Primary

Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat

Time frame: 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-24 Hours	41.2 Percentage dose	Standard Deviation 46.5
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-48 Hours	64.4 Percentage dose	Standard Deviation 40.6
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-72 Hours	84.4 Percentage dose	Standard Deviation 15.7
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-96 Hours	93.2 Percentage dose	Standard Deviation 7.8
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-120 Hours	96.3 Percentage dose	Standard Deviation 2.9
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-144 Hours	97.0 Percentage dose	Standard Deviation 2.7
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat	0-168 Hours	97.1 Percentage dose	Standard Deviation 2.7

Primary

Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat

Urine samples were collected at indicated time points and total radioactivity measurement was done using LSC. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.

Time frame: 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose

Population: PK Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-24 Hours	0.04 Percentage dose	Standard Deviation 0.03
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-48 Hours	0.04 Percentage dose	Standard Deviation 0.03
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-72 Hours	0.04 Percentage dose	Standard Deviation 0.03
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-96 Hours	0.04 Percentage dose	Standard Deviation 0.03
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-120 Hours	0.04 Percentage dose	Standard Deviation 0.03
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-144 Hours	0.04 Percentage dose	Standard Deviation 0.03
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat	0-168 Hours	0.04 Percentage dose	Standard Deviation 0.03

Primary

Period 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	6.25 Hours	Geometric Coefficient of Variation 64.3

Primary

Period 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	98.3 Hours	Geometric Coefficient of Variation 13.7

Primary

Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (MEDIAN)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	7.50 Hours

Primary

Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: PK Population

Arm	Measure	Value (MEDIAN)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	0.50 Hours

Secondary

Change From Baseline in DBP at Follow-up Visit (Day 34)

DBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame: Baseline and Day 34 (post Day 1 of Period 1 dosing)

Population: Safety Population

Arm	Measure	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Change From Baseline in DBP at Follow-up Visit (Day 34)	1.2 Millimeters of mercury	Standard Deviation 6.66

Secondary

Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)

Pulse rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value

Time frame: Baseline and Day 34 (post Day 1 of Period 1 dosing)

Population: Safety Population

Arm	Measure	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)	2.8 Beats per minute	Standard Deviation 7.79

Secondary

Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)

Respiratory rate was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame: Baseline and Day 34 (post Day 1 of Period 1 dosing)

Population: Safety Population

Arm	Measure	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)	-1.7 Breaths per minute	Standard Deviation 3.67

Secondary

Change From Baseline in SBP at Follow-up Visit (Day 34)

SBP was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value

Time frame: Baseline and Day 34 (post Day 1 of Period 1 dosing)

Population: Safety Population

Arm	Measure	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Change From Baseline in SBP at Follow-up Visit (Day 34)	2.4 Millimeters of mercury	Standard Deviation 8.96

Secondary

Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)

Tympanic membrane temperature was measured in a semi-recumbent position after 5 minutes of rest for the participant. Mean of the triplicate pre-dose assessments on Day 1 of treatment period 1 was considered as Baseline value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame: Baseline and Day 34 (post Day 1 of Period 1 dosing)

Population: Safety Population

Arm	Measure	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)	0.3 Degree Celsius	Standard Deviation 0.37

Secondary

Number of Participants With Abnormal Urinalysis Results by Dipstick Method

Urine samples were collected to assess urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine urobilinogen, urine nitrite and urine leukocyte esterase by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter can be read as negative (-) and positive (+) indicating proportional concentrations in the urine sample. Number of participants who had abnormal findings in any of these urinalysis parameters are presented.

Time frame: Up to 34 days

Population: Safety Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Abnormal Urinalysis Results by Dipstick Method	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Abnormal Urinalysis Results by Dipstick Method	0 Participants

Secondary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study treatment. An SAE is 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 34 days

Population: Safety Population comprised of all participants who received at least one dose of study treatment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any AEs	3 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any SAEs	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any AEs	3 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any SAEs	0 Participants

Secondary

Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters

Full 12-lead ECGs were recorded with the participants in a supine position. 12-lead ECGs were obtained using an automated ECG machine that measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals and calculated heart rate. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with clinically significant abnormal findings for ECG parameters at worst-case post Baseline are presented.

Time frame: Up to 34 days

Population: Safety Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters	0 Participants

Secondary

Number of Participants With Worst Case Chemistry Results Relative to Normal Range

Blood samples were collected to analyze the following clinical chemistry parameters; alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, calcium, chloride, cholesterol, creatinine, direct bilirubin, globulin, glucose, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, phosphate, potassium, protein, sodium, triglycerides, urate and urea. Participants were counted in the worst case category if their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.

Time frame: Up to 34 days

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urea, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALT, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALT, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Albumin, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Albumin, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Albumin, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALP, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALP, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	AST, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	AST, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	AST, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Bilirubin, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Bilirubin, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Bilirubin, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Calcium, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Calcium, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Calcium, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Chloride, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Chloride, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Chloride, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Cholesterol, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Cholesterol, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Cholesterol, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Creatinine, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Creatinine, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Creatinine, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Direct Bilirubin, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Direct Bilirubin, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Direct Bilirubin, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Globulin, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Globulin, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Globulin, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Glucose, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	HDL Cholesterol, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	HDL Cholesterol, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	HDL Cholesterol, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	LDL Cholesterol, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	LDL Cholesterol, To normal or no change	3 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	LDL Cholesterol, To high	3 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Phosphate, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Phosphate, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Protein, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Protein, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Sodium, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Sodium, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urate, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urate, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urate, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urea, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urea, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALT, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALP, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Glucose, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Glucose, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Phosphate, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Potassium, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Potassium, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Potassium, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Protein, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Sodium, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Triglycerides, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Triglycerides, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Triglycerides, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	HDL Cholesterol, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALT, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Albumin, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALT, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	HDL Cholesterol, To normal or no change	5 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALT, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Triglycerides, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Albumin, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	HDL Cholesterol, To high	1 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Albumin, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	AST, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Bilirubin, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALP, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALP, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	LDL Cholesterol, To normal or no change	5 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	ALP, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Globulin, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	AST, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	LDL Cholesterol, To high	1 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	AST, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Glucose, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Phosphate, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Bilirubin, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Phosphate, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Protein, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Bilirubin, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Potassium, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Calcium, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Glucose, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Calcium, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Protein, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Calcium, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Triglycerides, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Chloride, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Protein, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Chloride, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Glucose, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Chloride, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Sodium, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Cholesterol, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	LDL Cholesterol, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Cholesterol, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Sodium, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Cholesterol, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Triglycerides, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Creatinine, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urate, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Creatinine, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Phosphate, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Creatinine, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urate, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Direct Bilirubin, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Sodium, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Direct Bilirubin, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urate, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Direct Bilirubin, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Potassium, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Globulin, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urea, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urea, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Globulin, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Potassium, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Chemistry Results Relative to Normal Range	Urea, To high	0 Participants

Secondary

Number of Participants With Worst Case Hematology Results Relative to Normal Range

Blood samples were collected to analyze the following hematology parameters; Basophils, Eosinophils, Erythrocytes mean corpuscular volume (MCV), Erythrocytes mean corpuscular hemoglobin (MCH), Erythrocytes, Hematocrit (HCT), Hemoglobin (Hb), Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes and Reticulocytes/Erythrocytes. Participants were counted in the worst case category if their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.

Time frame: Up to 34 days

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Basophils, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Basophils, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Eosinophils, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Eosinophils, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Eosinophils, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCV, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCV, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCH, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCH, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Erythrocytes, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Erythrocytes, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Erythrocytes, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	HCT, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	HCT, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Hb, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Hb, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Leukocytes, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Lymphocytes, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Lymphocytes, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Monocytes, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Monocytes, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Monocytes, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Neutrophils, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Neutrophils, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Neutrophils, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Platelets, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Platelets, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Platelets, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes/Erythrocytes, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes/Erythrocyte, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes/Erythrocytes, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCV, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCH, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	HCT, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Hb, To high	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Leukocytes, To low	0 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Leukocytes, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Lymphocytes, To normal or no change	6 Participants
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Basophils, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Leukocytes, To normal or no change	5 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Monocytes, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Basophils, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Basophils, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Basophils, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Monocytes, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Eosinophils, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Eosinophils, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Monocytes, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Eosinophils, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCV, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Leukocytes, To low	1 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCV, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Neutrophils, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCV, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCH, To low	1 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes/Erythrocytes, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCH, To normal or no change	5 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Neutrophils, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	MCH, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Hb, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Erythrocytes, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Neutrophils, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Erythrocytes, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes/Erythrocyte, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Erythrocytes, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	HCT, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Platelets, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	HCT, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Lymphocytes, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	HCT, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Platelets, To normal or no change	6 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Hb, To low	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes/Erythrocytes, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Platelets, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Leukocytes, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Hb, To high	0 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Lymphocytes, To low	1 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Lymphocytes, To normal or no change	5 Participants
[14C]-Linerixibat 90 Milligram Oral Solution	Number of Participants With Worst Case Hematology Results Relative to Normal Range	Reticulocytes, To low	0 Participants

Secondary

Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points	Day 1 (4 Hours)	-1.2 Millimeters of mercury	Standard Deviation 4.11
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points	Day 8	2.0 Millimeters of mercury	Standard Deviation 8.81

Secondary

Period 1: Change From Baseline in Pulse Rate at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Pulse Rate at Indicated Time-points	Day 1 (4 Hours)	1.3 Beats per minute	Standard Deviation 4.2
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Pulse Rate at Indicated Time-points	Day 8	1.9 Beats per minute	Standard Deviation 4.02

Secondary

Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Day 1 (4 Hours)	0.0 Breaths per minute	Standard Deviation 2.19
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Day 8	1.0 Breaths per minute	Standard Deviation 4.15

Secondary

Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points	Day 1 (4 Hours)	5.2 Millimeters of mercury	Standard Deviation 11.16
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points	Day 8	6.6 Millimeters of mercury	Standard Deviation 7.68

Secondary

Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points	Day 1 (4 Hours)	0.4 Degree Celsius	Standard Deviation 0.37
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points	Day 8	-0.4 Degree Celsius	Standard Deviation 0.63

Secondary

Period 2: Change From Baseline in DBP at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in DBP at Indicated Time-points	Day 1 (4 Hours)	-2.4 Millimeters of mercury	Standard Deviation 7.27
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in DBP at Indicated Time-points	Day 8	2.1 Millimeters of mercury	Standard Deviation 6.56

Secondary

Period 2: Change From Baseline in Pulse Rate at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in Pulse Rate at Indicated Time-points	Day 1 (4 Hours)	-0.6 Beats per minute	Standard Deviation 4.2
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in Pulse Rate at Indicated Time-points	Day 8	1.3 Beats per minute	Standard Deviation 2.6

Secondary

Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points	Day 1 (4 Hours)	-0.7 Breaths per minute	Standard Deviation 1.63
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points	Day 8	-0.7 Breaths per minute	Standard Deviation 2.73

Secondary

Period 2: Change From Baseline in SBP at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in SBP at Indicated Time-points	Day 1 (4 Hours)	-1.1 Millimeters of mercury	Standard Deviation 8.73
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in SBP at Indicated Time-points	Day 8	6.5 Millimeters of mercury	Standard Deviation 6.39

Secondary

Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points

Time frame: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points	Day 1 (4 Hours)	0.2 Degree Celsius	Standard Deviation 0.58
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV	Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points	Day 8	-0.4 Degree Celsius	Standard Deviation 0.56

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat

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Period 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Period 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Period 1: AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Period 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Percentage of Drug Escaping First-pass Hepatic Clearance (Fh) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat

Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.

Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat

Period 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat

Period 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

Period 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

Period 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution

Period 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution

Period 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat

Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat

Period 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

Change From Baseline in DBP at Follow-up Visit (Day 34)

Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)

Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)

Change From Baseline in SBP at Follow-up Visit (Day 34)

Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)

Number of Participants With Abnormal Urinalysis Results by Dipstick Method

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters

Number of Participants With Worst Case Chemistry Results Relative to Normal Range

Number of Participants With Worst Case Hematology Results Relative to Normal Range

Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points

Period 1: Change From Baseline in Pulse Rate at Indicated Time-points

Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points

Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points

Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points

Period 2: Change From Baseline in DBP at Indicated Time-points

Period 2: Change From Baseline in Pulse Rate at Indicated Time-points

Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points

Period 2: Change From Baseline in SBP at Indicated Time-points

Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points