Trial Outcomes & Findings for Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat (NCT NCT03992014)

NCT ID: NCT03992014

Last Updated: 2020-06-26

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

6 participants

Primary outcome timeframe

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

Results posted on

2020-06-26

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.
Treatment Period 1 (8 Days) STARTED	6
Treatment Period 1 (8 Days) COMPLETED	6
Treatment Period 1 (8 Days) NOT COMPLETED	0
Washout Period (7 Days) STARTED	6
Washout Period (7 Days) COMPLETED	6
Washout Period (7 Days) NOT COMPLETED	0
Treatment Period 2 (8 Days) STARTED	6
Treatment Period 2 (8 Days) COMPLETED	6
Treatment Period 2 (8 Days) NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol n=6 Participants 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.
Age, Continuous	41.2 Years STANDARD_DEVIATION 8.13 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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 outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=3 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 Interval 0.5 to 5.5	—
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 Interval 0.983 to 2.5	—

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution	7.50 Hours Interval 2.0 to 48.1	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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 outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=3 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=1 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat	2300 Hours*picogram equivalent per milliliter Geometric Coefficient of Variation NA Not applicable (NA) indicates geometric coefficient of variation could not be calculated as a single participant was analyzed.	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat	738 Picogram equivalent per milliliter Geometric Coefficient of Variation 23.6	—

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat	1.49 Hours Interval 0.983 to 2.0	—

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution	0.50 Hours Interval 0.5 to 1.0	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=1 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat	0.733 Hours Geometric Coefficient of Variation NA NA indicates geometric coefficient of variation could not be calculated as a single participant was analyzed.	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=5 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=5 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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 outcome

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

Population: PK Population

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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	—
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	—
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	—
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	—
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	—
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 outcome

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

Population: PK Population.

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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	—
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	—
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	—
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	—
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	—
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 outcome

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

Population: PK Population

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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	—
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	—
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	—
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	—
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	—
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	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=5 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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	—
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	—
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: Up to 34 days

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

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution n=6 Participants Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 34 days

Population: Safety Population

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%.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution n=6 Participants Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Number of Participants With Worst Case Hematology Results Relative to Normal Range Basophils, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Basophils, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Basophils, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Eosinophils, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Eosinophils, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Eosinophils, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range MCV, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range MCV, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range MCV, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range MCH, To low	0 Participants	1 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range MCH, To normal or no change	6 Participants	5 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range MCH, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Erythrocytes, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Erythrocytes, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Erythrocytes, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range HCT, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range HCT, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range HCT, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Hb, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Hb, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Hb, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Leukocytes, To low	0 Participants	1 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Leukocytes, To normal or no change	6 Participants	5 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Leukocytes, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Lymphocytes, To low	0 Participants	1 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Lymphocytes, To normal or no change	6 Participants	5 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Lymphocytes, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Monocytes, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Monocytes, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Monocytes, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Neutrophils, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Neutrophils, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Neutrophils, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Platelets, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Platelets, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Platelets, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Reticulocytes, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Reticulocytes, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Reticulocytes, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Reticulocytes/Erythrocytes, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Reticulocytes/Erythrocyte, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range Reticulocytes/Erythrocytes, To high	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 34 days

Population: Safety Population

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%.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution n=6 Participants Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Number of Participants With Worst Case Chemistry Results Relative to Normal Range ALP, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range ALT, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range ALT, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range ALT, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Albumin, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Albumin, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Albumin, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range ALP, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range ALP, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range AST, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range AST, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range AST, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Bilirubin, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Bilirubin, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Bilirubin, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Calcium, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Calcium, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Calcium, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Chloride, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Chloride, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Chloride, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Cholesterol, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Cholesterol, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Cholesterol, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Creatinine, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Creatinine, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Creatinine, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Direct Bilirubin, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Direct Bilirubin, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Direct Bilirubin, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Globulin, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Globulin, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Globulin, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Glucose, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Glucose, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Glucose, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range HDL Cholesterol, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range HDL Cholesterol, To normal or no change	6 Participants	5 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range HDL Cholesterol, To high	0 Participants	1 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range LDL Cholesterol, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range LDL Cholesterol, To normal or no change	3 Participants	5 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range LDL Cholesterol, To high	3 Participants	1 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Phosphate, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Phosphate, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Phosphate, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Potassium, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Potassium, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Potassium, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Protein, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Protein, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Protein, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Sodium, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Sodium, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Sodium, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Triglycerides, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Triglycerides, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Triglycerides, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Urate, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Urate, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Urate, To high	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Urea, To low	0 Participants	0 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Urea, To normal or no change	6 Participants	6 Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range Urea, To high	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 34 days

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution n=6 Participants Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Number of Participants With Abnormal Urinalysis Results by Dipstick Method	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 34 days

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution n=6 Participants Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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 outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 2: Change From Baseline in DBP at Indicated Time-points Day 1 (4 Hours)	-2.4 Millimeters of mercury Standard Deviation 7.27	—
Period 2: Change From Baseline in DBP at Indicated Time-points Day 8	2.1 Millimeters of mercury Standard Deviation 6.56	—

SECONDARY outcome

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

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Change From Baseline in DBP at Follow-up Visit (Day 34)	1.2 Millimeters of mercury Standard Deviation 6.66	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 1: Change From Baseline in Pulse Rate at Indicated Time-points Day 1 (4 Hours)	1.3 Beats per minute Standard Deviation 4.20	—
Period 1: Change From Baseline in Pulse Rate at Indicated Time-points Day 8	1.9 Beats per minute Standard Deviation 4.02	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 2: Change From Baseline in Pulse Rate at Indicated Time-points Day 1 (4 Hours)	-0.6 Beats per minute Standard Deviation 4.20	—
Period 2: Change From Baseline in Pulse Rate at Indicated Time-points Day 8	1.3 Beats per minute Standard Deviation 2.60	—

SECONDARY outcome

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

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)	2.8 Beats per minute Standard Deviation 7.79	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
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 outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Period 2: Change From Baseline in SBP at Indicated Time-points Day 1 (4 Hours)	-1.1 Millimeters of mercury Standard Deviation 8.73	—
Period 2: Change From Baseline in SBP at Indicated Time-points Day 8	6.5 Millimeters of mercury Standard Deviation 6.39	—

SECONDARY outcome

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

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Change From Baseline in SBP at Follow-up Visit (Day 34)	2.4 Millimeters of mercury Standard Deviation 8.96	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

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

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points Day 8	1.0 Breaths per minute Standard Deviation 4.15	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points Day 8	-0.7 Breaths per minute Standard Deviation 2.73	—

SECONDARY outcome

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

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)	-1.7 Breaths per minute Standard Deviation 3.67	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points Day 8	-0.4 Degree Celsius Standard Deviation 0.63	—

SECONDARY outcome

Timeframe: Baseline, Day 1 (4 Hours) and Day 8

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
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	—
Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points Day 8	-0.4 Degree Celsius Standard Deviation 0.56	—

SECONDARY outcome

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

Population: Safety Population

Outcome measures

Outcome measures
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 Participants Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1.	[14C]-Linerixibat 90 Milligram Oral Solution Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)	0.3 Degree Celsius Standard Deviation 0.37	—

Adverse Events

Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

[14C]-Linerixibat 90 Milligram Oral Solution

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV n=6 participants at risk Eligible participants received 25 mL of intravenous (IV) radiolabelled \[14C\]-Linerixibat 100 microgram (μg) infused over 3 hours immediately after the Linerixibat 90 mg (two 45 mg) tablets orally in fasted state on Day 1 of treatment period 1	[14C]-Linerixibat 90 Milligram Oral Solution n=6 participants at risk Participants received single 60 mL oral solution of 90 mg \[14C\]-Linerixibat on Day 1 of treatment period 2 in fasted state
Skin and subcutaneous tissue disorders Erythema	0.00% 0/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment
Gastrointestinal disorders Abdominal discomfort	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment	0.00% 0/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment
Gastrointestinal disorders Constipation	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment	0.00% 0/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment
Nervous system disorders Headache	16.7% 1/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment	0.00% 0/6 • SAEs and non-serious AEs were collected from the start of study treatment up to Day 34. SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER