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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Linerixibat + [14C]-linerixibat | Experimental | Subjects will receive a single oral dose of linerixibat 90 milligram (mg) (2*45 mg) tablets concomitantly with [14C]-linerixibat 100 microgram (approximately 9.25 kilobecquerel; 250 nano curie) IV infusion for 3 hours, after an overnight fast that continues for 2 hours after the oral dose/start of IV infusion, small standard high-fat meal will be given on Day 1 in treatment Period 1; followed by a single oral dose of [14C]-linerixibat 90 mg (approximately 4.96 megabecquerel; 134.1 micro curie) solution on Day 1 in treatment Period 2. A wash out period of at least 13 days will be maintained between oral doses of treatment periods. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linerixibat tablet | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria
Exclusion Criteria
Only healthy male subjects will be enrolled in this study.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7EW | United Kingdom |
IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (8 Days) |
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| Washout Period (7 Days) |
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| Treatment Period 2 (8 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram per milliliter | 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 |
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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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 11, 2019 | May 28, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 17, 2020 | May 28, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002779 | Cholestasis |
| ID | Term |
|---|---|
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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Subjects will receive linerixibat tablets concomitantly with [14C]-linerixibat IV infusion in treatment Period 1 and [14C]-linerixibat oral solution in treatment Period 2.
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This will be an open-label study. Hence, there will be no masking.
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| [14C]-linerixibat intravenous infusion | Drug | [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. |
|
| Linerixibat oral solution | Drug | 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. |
|
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
| 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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). | 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 |
| 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. | 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 |
| 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. | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
| 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. | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
| 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. | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
| Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral 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. | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
| Up to 34 days |
| 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%. | Up to 34 days |
| 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%. | Up to 34 days |
| 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. | Up to 34 days |
| 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. | Up to 34 days |
| Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points | 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. | Baseline, Day 1 (4 Hours) and Day 8 |
| Period 2: Change From Baseline in DBP at Indicated Time-points | 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. | Baseline, Day 1 (4 Hours) and Day 8 |
| 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. | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
| Period 1: Change From Baseline in Pulse Rate at Indicated Time-points | 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 | Baseline, Day 1 (4 Hours) and Day 8 |
| Period 2: Change From Baseline in Pulse Rate at Indicated Time-points | 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 | Baseline, Day 1 (4 Hours) and Day 8 |
| 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 | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
| Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points | 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 | Baseline, Day 1 (4 Hours) and Day 8 |
| Period 2: Change From Baseline in SBP at Indicated Time-points | 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 | Baseline, Day 1 (4 Hours) and Day 8 |
| 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 | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
| Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points | 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 | Baseline, Day 1 (4 Hours) and Day 8 |
| Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points | 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. | Baseline, Day 1 (4 Hours) and Day 8 |
| 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. | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
| Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points | 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. | Baseline, Day 1 (4 Hours) and Day 8 |
| Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points | 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. | Baseline, Day 1 (4 Hours) and Day 8 |
| 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. | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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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.
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| 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. | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram per milliliter | 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 |
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| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram per milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram per milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram per milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram per milliliter | 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 |
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| 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. | PK Population | Posted | Median | Full Range | Hours | 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 |
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| 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. | PK Population | Posted | Median | Full Range | Hours | 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 |
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| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| 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. | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| 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. | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram equivalent per milliliter | 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 |
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| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram equivalent per milliliter | 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 |
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| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram equivalent per milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram equivalent per milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram equivalent per milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram equivalent per milliliter | 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 |
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| 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. | PK Population | Posted | Median | Full Range | Hours | 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 |
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| 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. | PK Population | Posted | Median | Full Range | Hours | 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 |
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| 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. | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Milliliter | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Milliliters per minute | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Milliliters per minute | 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 |
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| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage bioavailability | 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 |
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| 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). | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of drug escaped | 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 |
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| 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. | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of drug absorbed | 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 |
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| 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. | PK Population | Posted | Mean | Standard Deviation | Percentage dose | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
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| 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. | PK Population. | Posted | Mean | Standard Deviation | Percentage dose | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
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| 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. | PK Population | Posted | Mean | Standard Deviation | Percentage dose | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
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| Primary | Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral 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. | PK Population. Only those participants with data available at the specified data points were analyzed. | Posted | Mean | Standard Deviation | Percentage dose | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose |
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| 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. | Safety Population comprised of all participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to 34 days |
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| 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%. | Safety Population | Posted | Count of Participants | Participants | Up to 34 days |
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| 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%. | Safety Population | Posted | Count of Participants | Participants | Up to 34 days |
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| 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. | Safety Population | Posted | Count of Participants | Participants | Up to 34 days |
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| 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. | Safety Population | Posted | Count of Participants | Participants | Up to 34 days |
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| Secondary | Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points | 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline, Day 1 (4 Hours) and Day 8 |
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| Secondary | Period 2: Change From Baseline in DBP at Indicated Time-points | 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline, Day 1 (4 Hours) and Day 8 |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
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| Secondary | Period 1: Change From Baseline in Pulse Rate at Indicated Time-points | 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 | Safety Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline, Day 1 (4 Hours) and Day 8 |
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| Secondary | Period 2: Change From Baseline in Pulse Rate at Indicated Time-points | 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 | Safety Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline, Day 1 (4 Hours) and Day 8 |
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| 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 | Safety Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
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| Secondary | Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points | 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 | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline, Day 1 (4 Hours) and Day 8 |
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| Secondary | Period 2: Change From Baseline in SBP at Indicated Time-points | 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 | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline, Day 1 (4 Hours) and Day 8 |
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| 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 | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
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| Secondary | Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points | 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 | Safety Population | Posted | Mean | Standard Deviation | Breaths per minute | Baseline, Day 1 (4 Hours) and Day 8 |
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| Secondary | Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points | 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. | Safety Population | Posted | Mean | Standard Deviation | Breaths per minute | Baseline, Day 1 (4 Hours) and Day 8 |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Breaths per minute | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
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| Secondary | Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points | 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. | Safety Population | Posted | Mean | Standard Deviation | Degree Celsius | Baseline, Day 1 (4 Hours) and Day 8 |
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| Secondary | Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points | 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. | Safety Population | Posted | Mean | Standard Deviation | Degree Celsius | Baseline, Day 1 (4 Hours) and Day 8 |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Degree Celsius | Baseline and Day 34 (post Day 1 of Period 1 dosing) |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 3 |
| 6 |
| EG001 | [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 | 0 | 6 | 0 | 6 | 3 | 6 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
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.
| Title | Measurements |
|---|---|
|
| 0-96 Hours |
|
| 0-120 Hours |
|
| 0-144 Hours |
|
| 0-168 Hours |
|
| Title | Measurements |
|---|---|
|
| 0-96 Hours |
|
| 0-120 Hours |
|
| 0-144 Hours |
|
| 0-168 Hours |
|
| Title | Measurements |
|---|---|
|
| 0-96 Hours |
|
| 0-120 Hours |
|
| 0-144 Hours |
|
| 0-168 Hours |
|
| Title | Measurements |
|---|---|
|
| 0-96 Hours |
|
| 0-120 Hours |
|
| 0-144 Hours |
|
| 0-168 Hours |
|
| Basophils, To high |
|
| Eosinophils, To low |
|
| Eosinophils, To normal or no change |
|
| Eosinophils, To high |
|
| MCV, To low |
|
| MCV, To normal or no change |
|
| MCV, To high |
|
| MCH, To low |
|
| MCH, To normal or no change |
|
| MCH, To high |
|
| Erythrocytes, To low |
|
| Erythrocytes, To normal or no change |
|
| Erythrocytes, To high |
|
| HCT, To low |
|
| HCT, To normal or no change |
|
| HCT, To high |
|
| Hb, To low |
|
| Hb, To normal or no change |
|
| Hb, To high |
|
| Leukocytes, To low |
|
| Leukocytes, To normal or no change |
|
| Leukocytes, To high |
|
| Lymphocytes, To low |
|
| Lymphocytes, To normal or no change |
|
| Lymphocytes, To high |
|
| Monocytes, To low |
|
| Monocytes, To normal or no change |
|
| Monocytes, To high |
|
| Neutrophils, To low |
|
| Neutrophils, To normal or no change |
|
| Neutrophils, To high |
|
| Platelets, To low |
|
| Platelets, To normal or no change |
|
| Platelets, To high |
|
| Reticulocytes, To low |
|
| Reticulocytes, To normal or no change |
|
| Reticulocytes, To high |
|
| Reticulocytes/Erythrocytes, To low |
|
| Reticulocytes/Erythrocyte, To normal or no change |
|
| Reticulocytes/Erythrocytes, To high |
|
| ALT, To high |
|
| Albumin, To low |
|
| Albumin, To normal or no change |
|
| Albumin, To high |
|
| ALP, To low |
|
| ALP, To normal or no change |
|
| ALP, To high |
|
| AST, To low |
|
| AST, To normal or no change |
|
| AST, To high |
|
| Bilirubin, To low |
|
| Bilirubin, To normal or no change |
|
| Bilirubin, To high |
|
| Calcium, To low |
|
| Calcium, To normal or no change |
|
| Calcium, To high |
|
| Chloride, To low |
|
| Chloride, To normal or no change |
|
| Chloride, To high |
|
| Cholesterol, To low |
|
| Cholesterol, To normal or no change |
|
| Cholesterol, To high |
|
| Creatinine, To low |
|
| Creatinine, To normal or no change |
|
| Creatinine, To high |
|
| Direct Bilirubin, To low |
|
| Direct Bilirubin, To normal or no change |
|
| Direct Bilirubin, To high |
|
| Globulin, To low |
|
| Globulin, To normal or no change |
|
| Globulin, To high |
|
| Glucose, To low |
|
| Glucose, To normal or no change |
|
| Glucose, To high |
|
| HDL Cholesterol, To low |
|
| HDL Cholesterol, To normal or no change |
|
| HDL Cholesterol, To high |
|
| LDL Cholesterol, To low |
|
| LDL Cholesterol, To normal or no change |
|
| LDL Cholesterol, To high |
|
| Phosphate, To low |
|
| Phosphate, To normal or no change |
|
| Phosphate, To high |
|
| Potassium, To low |
|
| Potassium, To normal or no change |
|
| Potassium, To high |
|
| Protein, To low |
|
| Protein, To normal or no change |
|
| Protein, To high |
|
| Sodium, To low |
|
| Sodium, To normal or no change |
|
| Sodium, To high |
|
| Triglycerides, To low |
|
| Triglycerides, To normal or no change |
|
| Triglycerides, To high |
|
| Urate, To low |
|
| Urate, To normal or no change |
|
| Urate, To high |
|
| Urea, To low |
|
| Urea, To normal or no change |
|
| Urea, To high |
|