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CompletedNCT03992014Updated Jun 26, 2020Results posted

Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat

A Phase 1 interventional study of Linerixibat tablet and [14C]-linerixibat intravenous infusion in Cholestasis, sponsored by GlaxoSmithKline. Completed at 1 site in United Kingdom. Open to male participants aged 30 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-06-26.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
6
Allocation
Non-randomized
Ages
30 Years to 55 Years
Sex
Male
01

Study summary

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

02

Conditions studied

  • Cholestasis

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Keywords

  • [14C]-linerixibat
  • GSK2330672
  • Microtracer dose
03

In context

Cholestasis

220 studies on the registry are indexed under Cholestasis; 37 are open to participants now.

This study's enrollment of 6 is below the median of 55 across 135 interventional studies indexed under Cholestasis.

Browse Cholestasis studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 55 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  • Aged 30 to 55 years, inclusive, at the time of signing the informed consent.
  • Healthy, as determined by the investigator or medically qualified designee, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG. A subject with a clinical abnormality or laboratory parameter (i.e., outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • History of regular bowel movements (averaging one or more bowel movements per day).
  • Non-smoker, or ex-smoker who hasn't regularly smoked for the 6 months before screening.
  • Body weight of 50 kilogram and above, and body mass index (BMI) within the range 19.0 to 31.0 kilogram per square meter (kg/m\^2) (inclusive).
  • Male only. Subjects must agree to use contraception as follows: subjects with female partners of childbearing potential must agree to use a condom from the time of first dose of study intervention until 1 month after their last dose.
  • Capable of giving signed informed consent.

Exclusion criteria

Exclusion Criteria

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Subjects with a history of cholecystectomy must be excluded.
  • Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history) clinical laboratory tests, or 12-lead ECG.
  • Current episode, recent history, or chronic history of diarrhoea.
  • Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • Any current medical condition (example given [e.g.], psychiatric disorder, senility, dementia, or other condition), clinical or laboratory abnormality, or examination finding that the investigator considers would put the subjects at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
  • Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.
  • Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >21 units. One unit is equivalent to 8 gram of alcohol: a glass (approximately 240 mL) of beer, 1 small glass (approximately 100 mL) of wine or 1 (approximately 25 mL) measure of spirits.
  • History of or regular use of tobacco- or nicotine-containing products in the 6 months prior to screening.
  • Past or intended use of over-the-counter or prescription medication, including analgesics (e.g., paracetamol), herbal medications, or grapefruit and Seville orange juices within 14 days prior to the first dose of study intervention until completion of the follow-up visit.
  • Administration of any other Ileal bile acid transporter (IBAT) inhibitor in the 3 months prior to screening.
  • Current enrolment in a clinical trial; recent participation in a clinical trial and has received an investigational product within 3 months before the first dose in the current study.
  • Exposure to more than 4 new chemical entities within 12 months before the first dose in the current study.
  • Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A subjects previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study.
  • Received a total body radiation dose of greater than 10.0 millisievert (upper limit of International Commission on Radiological Protection [IRCP] category II) or exposure to significant radiation (e.g., serial x-ray or computed tomography [CT] scans, barium meal, etc.) in the 3 years before this study.
  • Alanine transaminase (ALT) >1.5* upper limit of normal (ULN).
  • Bilirubin >1.5*ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent [%]).
  • Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study intervention.
  • Screening estimated glomerular filtration rate (eGFR) \<45 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2) based on the Modification of Diet in Renal Disease (MDRD) Study equation.
  • Positive pre-study drug/alcohol screen.
  • Urinary cotinine levels indicative of smoking.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • QT duration corrected for heart rate by Fridericia's formula >450 millisecond on ECG performed at Screening
  • At screening or prior to the first dose, a supine blood pressure that is persistently higher than 140/90 millimeters of mercury (mmHg) taken in triplicate, unless deemed not clinically significant by the investigator.
  • At screening or prior to the first dose, a supine mean heart rate outside the range of 40-100 beats per minute, unless deemed not clinically significant by the investigator.
  • Has had an occupation which requires monitoring for radiation exposure, nuclear medicine procedures, or excessive x-rays within the past 12 months.
  • Unable to refrain from consumption of prohibited food and drinks from 7 days before the first dose of study medication until the follow up visit.
  • Loss of more than 400 mL blood during the 3 months before screening, e.g. as a blood donor, or plan to donate blood or blood products in the 3 months after the end of the trial.
  • Unwillingness or inability to follow the procedures outlines in the protocol, including the use of the string bile collection device.
  • History of sensitivity to linerixibat, or their components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
6 participants (actual)

Study arms

  • Experimental
    Linerixibat + [14C]-linerixibat

    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.

    Drug: Linerixibat tablet · Drug: [14C]-linerixibat intravenous infusion · Drug: Linerixibat oral solution

Interventions

  • DrugLinerixibat tablet

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

  • Drug[14C]-linerixibat intravenous infusion

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

  • DrugLinerixibat oral solution

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

06

What researchers measure

Primary outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  30. 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.

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

Secondary outcomes

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

    AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement.

    Time frame: Up to 34 days

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

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

    Time frame: Up to 34 days

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

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

    Time frame: Up to 34 days

  4. Number of Participants With Abnormal Urinalysis Results by Dipstick Method

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

    Time frame: Up to 34 days

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

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

    Time frame: Up to 34 days

  6. 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.

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

  7. 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.

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

  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.

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

  9. 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

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

  10. 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

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

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

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

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

  12. 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

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

  13. 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

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

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

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

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

  15. 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

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

  16. 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.

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

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

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

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

  18. 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.

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

  19. 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.

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

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

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

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

07

Results

Posted Jun 26, 2020

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.

Treatment Period 1 (8 Days)
Participant flow — Treatment Period 1 (8 Days)
MilestoneLinerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Started6
Completed6
Not completed0
Washout Period (7 Days)
Participant flow — Washout Period (7 Days)
MilestoneLinerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Started6
Completed6
Not completed0
Treatment Period 2 (8 Days)
Participant flow — Treatment Period 2 (8 Days)
MilestoneLinerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Started6
Completed6
Not completed0

Outcome measures

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

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram per milliliter
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
Hours*picogram per milliliterLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Linerixibat 90 mg oral tablets1554 ± 25.8
[14C] Linerixibat 100 μg IV1570 ± 26.7
PrimaryPeriod 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram per milliliter
Period 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution
Hours*picogram per milliliter[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: AUC(0-inf) of [14C]-Linerixibat Following Administration of Oral Dose of [14C]-Linerixibat Solution1634 ± 95.3
PrimaryPeriod 1: AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram per milliliter
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
Hours*picogram per milliliterLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Linerixibat 90 mg oral tablets749 ± 125
[14C] Linerixibat 100 μg IV1560 ± 26.8
PrimaryPeriod 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram per milliliter
Period 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution
Hours*picogram per milliliter[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: AUC(0-t) of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution1044 ± 79.4
PrimaryPeriod 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Picogram per milliliter
Period 1: Maximum Observed Concentration (Cmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat
Picogram per milliliterLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Linerixibat 90 mg oral tablets120 ± 108
[14C] Linerixibat 100 μg IV638 ± 27.3
PrimaryPeriod 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Picogram per milliliter
Period 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution
Picogram per milliliter[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: Cmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution158 ± 270
PrimaryPeriod 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Median · Hours
Period 1: Time of Occurrence of Cmax (Tmax) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat
HoursLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Linerixibat 90 mg oral tablets2.25 (0.500 to 5.50)
[14C] Linerixibat 100 μg IV1.49 (0.983 to 2.50)
PrimaryPeriod 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Median · Hours
Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution
Hours[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: Tmax of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution7.50 (2.00 to 48.1)
PrimaryPeriod 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours
Period 1: Terminal Phase Half-Life (t1/2) of Linerixibat and [14C]-Linerixibat Following Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat
HoursLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Linerixibat 90 mg oral tablets6.76 ± 124
[14C] Linerixibat 100 μg IV0.828 ± 18.3
PrimaryPeriod 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours
Period 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution
Hours[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: t1/2 of [14C]-Linerixibat Following Administration of Oral Dose of [14C] Linerixibat Solution6.25 ± 64.3
PrimaryPeriod 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram equivalent per milliliter
Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat
Hours*picogram equivalent per milliliter[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: AUC(0-inf) of Total Radioactivity Following IV Dose of [14C]-Linerixibat2300 ± NA
PrimaryPeriod 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram equivalent per milliliter
Period 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution
Hours*picogram equivalent per milliliter[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: AUC(0-inf) of Total Radioactivity Following Administration of Oral Dose of [14C]-Linerixibat Solution94740 ± 8.17
PrimaryPeriod 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram equivalent per milliliter
Period 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat
Hours*picogram equivalent per milliliter[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: AUC(0-t) of Total Radioactivity Following IV Dose of [14C]-Linerixibat1903 ± 22.3
PrimaryPeriod 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours*picogram equivalent per milliliter
Period 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution
Hours*picogram equivalent per milliliter[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: AUC(0-t) of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution67533 ± 11.3
PrimaryPeriod 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Picogram equivalent per milliliter
Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat
Picogram equivalent per milliliter[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: Cmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat738 ± 23.6
PrimaryPeriod 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Picogram equivalent per milliliter
Period 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution
Picogram equivalent per milliliter[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: Cmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution2784 ± 14.3
PrimaryPeriod 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Median · Hours
Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat
Hours[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: Tmax of Total Radioactivity Following IV Dose of [14C]-Linerixibat1.49 (0.983 to 2.00)
PrimaryPeriod 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Median · Hours
Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution
Hours[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: Tmax of Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution0.50 (0.500 to 1.00)
PrimaryPeriod 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours
Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat
Hours[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: t1/2 of [14C]-Linerixibat for Total Radioactivity Following IV Dose of [14C]-Linerixibat0.733 ± NA
PrimaryPeriod 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution

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

Time frame:
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Hours
Period 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution
Hours[14C]-Linerixibat 90 Milligram Oral Solution
Period 2: t1/2 of [14C]-Linerixibat for Total Radioactivity Following Administration of Oral Dose of [14C] Linerixibat Solution98.3 ± 13.7
PrimaryPeriod 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Milliliter
Period 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat
Milliliter[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: Volume of Distribution at Steady State (Vss) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat16340 ± 35.7
PrimaryPeriod 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Milliliters per minute
Period 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat
Milliliters per minute[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: Total Plasma Clearance (CL) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat1032 ± 27.3
PrimaryPeriod 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Milliliters per minute
Period 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat
Milliliters per minute[14C]-Linerixibat 100 Microgram Intravenous Infusion
Period 1: Hepatic Clearance (CLh) of [14C]-Linerixibat Following Administration of IV Dose of [14C]-Linerixibat867 ± 26.4
PrimaryPeriod 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Percentage bioavailability
Period 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat
Percentage bioavailabilityLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Period 1: Absolute Oral Bioavailability (F) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat0.0517 ± 120
PrimaryPeriod 1: Percentage of Drug Escaping First-pass Hepatic Clearance (Fh) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Percentage of drug escaped
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
Percentage of drug escapedLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Period 1: Percentage of Drug Escaping First-pass Hepatic Clearance (Fh) of Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat24.4 ± 68.4
PrimaryPeriod 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Reported as:
Geometric mean · Percentage of drug absorbed
Period 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat
Percentage of drug absorbedLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Period 1: Percentage of Drug Absorbed (Fa) for Linerixibat Following Administration of Oral Dose of Linerixibat and IV Dose of [14C]-Linerixibat0.167 ± 73.7
PrimaryPeriod 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.

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

Time frame:
0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose
Reported as:
Mean · Percentage dose
Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of IV Dose of [14C]-Linerixibat.
Percentage dose[14C]-Linerixibat 100 Microgram Intravenous Infusion
0-24 Hours16.4 ± 2.8
0-48 Hours16.4 ± 2.8
0-72 Hours16.5 ± 2.8
0-96 Hours16.5 ± 2.8
0-120 Hours16.5 ± 2.8
0-144 Hours16.5 ± 2.8
0-168 Hours16.5 ± 2.8
PrimaryPeriod 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat

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

Time frame:
0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose
Reported as:
Mean · Percentage dose
Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Urine Following Administration of Oral Dose of [14C]-Linerixibat
Percentage dose[14C]-Linerixibat 90 Milligram Oral Solution
0-24 Hours0.04 ± 0.03
0-48 Hours0.04 ± 0.03
0-72 Hours0.04 ± 0.03
0-96 Hours0.04 ± 0.03
0-120 Hours0.04 ± 0.03
0-144 Hours0.04 ± 0.03
0-168 Hours0.04 ± 0.03
PrimaryPeriod 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat

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

Time frame:
0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose
Reported as:
Mean · Percentage dose
Period 1: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of IV Dose of [14C]-Linerixibat
Percentage dose[14C]-Linerixibat 100 Microgram Intravenous Infusion
0-24 Hours33.4 ± 19.4
0-48 Hours43.6 ± 18.8
0-72 Hours61.3 ± 7.5
0-96 Hours67.8 ± 6.3
0-120 Hours68.8 ± 6.3
0-144 Hours69.1 ± 6.3
0-168 Hours69.2 ± 6.3
PrimaryPeriod 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.

Time frame:
0-24, 0-48, 0-72, 0-96, 0-120, 0-144 and 0-168 hours post-dose
Reported as:
Mean · Percentage dose
Period 2: Summary of Mean Cumulative Total Recovery (Percentage Excreted) in Feces Following Administration of Oral Dose of [14C]-Linerixibat
Percentage dose[14C]-Linerixibat 90 Milligram Oral Solution
0-24 Hours41.2 ± 46.5
0-48 Hours64.4 ± 40.6
0-72 Hours84.4 ± 15.7
0-96 Hours93.2 ± 7.8
0-120 Hours96.3 ± 2.9
0-144 Hours97.0 ± 2.7
0-168 Hours97.1 ± 2.7
SecondaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement.

Time frame:
Up to 34 days
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
ParticipantsLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV[14C]-Linerixibat 90 Milligram Oral Solution
Any AEs33
Any SAEs00
SecondaryNumber of Participants With Worst Case Hematology Results Relative to Normal Range

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

Time frame:
Up to 34 days
Reported as:
Count of participants · Participants
Number of Participants With Worst Case Hematology Results Relative to Normal Range
ParticipantsLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV[14C]-Linerixibat 90 Milligram Oral Solution
Basophils, To low00
Basophils, To normal or no change66
Basophils, To high00
Eosinophils, To low00
Eosinophils, To normal or no change66
Eosinophils, To high00
MCV, To low00
MCV, To normal or no change66
MCV, To high00
MCH, To low01
MCH, To normal or no change65
MCH, To high00
Erythrocytes, To low00
Erythrocytes, To normal or no change66
Erythrocytes, To high00
HCT, To low00
HCT, To normal or no change66
HCT, To high00
Hb, To low00
Hb, To normal or no change66
Hb, To high00
Leukocytes, To low01
Leukocytes, To normal or no change65
Leukocytes, To high00
Lymphocytes, To low01
Lymphocytes, To normal or no change65
Lymphocytes, To high00
Monocytes, To low00
Monocytes, To normal or no change66
Monocytes, To high00
Neutrophils, To low00
Neutrophils, To normal or no change66
Neutrophils, To high00
Platelets, To low00
Platelets, To normal or no change66
Platelets, To high00
Reticulocytes, To low00
Reticulocytes, To normal or no change66
Reticulocytes, To high00
Reticulocytes/Erythrocytes, To low00
Reticulocytes/Erythrocyte, To normal or no change66
Reticulocytes/Erythrocytes, To high00
SecondaryNumber of Participants With Worst Case Chemistry Results Relative to Normal Range

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

Time frame:
Up to 34 days
Reported as:
Count of participants · Participants
Number of Participants With Worst Case Chemistry Results Relative to Normal Range
ParticipantsLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV[14C]-Linerixibat 90 Milligram Oral Solution
ALT, To low00
ALT, To normal or no change66
ALT, To high00
Albumin, To low00
Albumin, To normal or no change66
Albumin, To high00
ALP, To low00
ALP, To normal or no change66
ALP, To high00
AST, To low00
AST, To normal or no change66
AST, To high00
Bilirubin, To low00
Bilirubin, To normal or no change66
Bilirubin, To high00
Calcium, To low00
Calcium, To normal or no change66
Calcium, To high00
Chloride, To low00
Chloride, To normal or no change66
Chloride, To high00
Cholesterol, To low00
Cholesterol, To normal or no change66
Cholesterol, To high00
Creatinine, To low00
Creatinine, To normal or no change66
Creatinine, To high00
Direct Bilirubin, To low00
Direct Bilirubin, To normal or no change66
Direct Bilirubin, To high00
Globulin, To low00
Globulin, To normal or no change66
Globulin, To high00
Glucose, To low00
Glucose, To normal or no change66
Glucose, To high00
HDL Cholesterol, To low00
HDL Cholesterol, To normal or no change65
HDL Cholesterol, To high01
LDL Cholesterol, To low00
LDL Cholesterol, To normal or no change35
LDL Cholesterol, To high31
Phosphate, To low00
Phosphate, To normal or no change66
Phosphate, To high00
Potassium, To low00
Potassium, To normal or no change66
Potassium, To high00
Protein, To low00
Protein, To normal or no change66
Protein, To high00
Sodium, To low00
Sodium, To normal or no change66
Sodium, To high00
Triglycerides, To low00
Triglycerides, To normal or no change66
Triglycerides, To high00
Urate, To low00
Urate, To normal or no change66
Urate, To high00
Urea, To low00
Urea, To normal or no change66
Urea, To high00
SecondaryNumber of Participants With Abnormal Urinalysis Results by Dipstick Method

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

Time frame:
Up to 34 days
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
ParticipantsLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV[14C]-Linerixibat 90 Milligram Oral Solution
Number of Participants With Abnormal Urinalysis Results by Dipstick Method00
SecondaryNumber of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters

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

Time frame:
Up to 34 days
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters
ParticipantsLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV[14C]-Linerixibat 90 Milligram Oral Solution
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters00
SecondaryPeriod 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.

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Millimeters of mercury
Period 1: Change From Baseline in Diastolic Blood Pressure (DBP) at Indicated Time-points
Millimeters of mercuryLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Day 1 (4 Hours)-1.2 ± 4.11
Day 82.0 ± 8.81
SecondaryPeriod 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.

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Millimeters of mercury
Period 2: Change From Baseline in DBP at Indicated Time-points
Millimeters of mercury[14C]-Linerixibat 90 Milligram Oral Solution
Day 1 (4 Hours)-2.4 ± 7.27
Day 82.1 ± 6.56
SecondaryChange From Baseline in DBP at Follow-up Visit (Day 34)

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

Time frame:
Baseline and Day 34 (post Day 1 of Period 1 dosing)
Reported as:
Mean · Millimeters of mercury
Change From Baseline in DBP at Follow-up Visit (Day 34)
Millimeters of mercury[14C]-Linerixibat 90 Milligram Oral Solution
Change From Baseline in DBP at Follow-up Visit (Day 34)1.2 ± 6.66
SecondaryPeriod 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

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Beats per minute
Period 1: Change From Baseline in Pulse Rate at Indicated Time-points
Beats per minuteLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Day 1 (4 Hours)1.3 ± 4.20
Day 81.9 ± 4.02
SecondaryPeriod 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

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Beats per minute
Period 2: Change From Baseline in Pulse Rate at Indicated Time-points
Beats per minute[14C]-Linerixibat 90 Milligram Oral Solution
Day 1 (4 Hours)-0.6 ± 4.20
Day 81.3 ± 2.60
SecondaryChange From Baseline in Pulse Rate at Follow-up Visit (Day 34)

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

Time frame:
Baseline and Day 34 (post Day 1 of Period 1 dosing)
Reported as:
Mean · Beats per minute
Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)
Beats per minute[14C]-Linerixibat 90 Milligram Oral Solution
Change From Baseline in Pulse Rate at Follow-up Visit (Day 34)2.8 ± 7.79
SecondaryPeriod 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

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Millimeters of mercury
Period 1: Change From Baseline in Systolic Blood Pressure (SBP) at Indicated Time-points
Millimeters of mercuryLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Day 1 (4 Hours)5.2 ± 11.16
Day 86.6 ± 7.68
SecondaryPeriod 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

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Millimeters of mercury
Period 2: Change From Baseline in SBP at Indicated Time-points
Millimeters of mercury[14C]-Linerixibat 90 Milligram Oral Solution
Day 1 (4 Hours)-1.1 ± 8.73
Day 86.5 ± 6.39
SecondaryChange From Baseline in SBP at Follow-up Visit (Day 34)

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

Time frame:
Baseline and Day 34 (post Day 1 of Period 1 dosing)
Reported as:
Mean · Millimeters of mercury
Change From Baseline in SBP at Follow-up Visit (Day 34)
Millimeters of mercury[14C]-Linerixibat 90 Milligram Oral Solution
Change From Baseline in SBP at Follow-up Visit (Day 34)2.4 ± 8.96
SecondaryPeriod 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

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Breaths per minute
Period 1: Change From Baseline in Respiratory Rate at Indicated Time-points
Breaths per minuteLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Day 1 (4 Hours)0.0 ± 2.19
Day 81.0 ± 4.15
SecondaryPeriod 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.

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Breaths per minute
Period 2: Change From Baseline in Respiratory Rate at Indicated Time-points
Breaths per minute[14C]-Linerixibat 90 Milligram Oral Solution
Day 1 (4 Hours)-0.7 ± 1.63
Day 8-0.7 ± 2.73
SecondaryChange From Baseline in Respiratory Rate at Follow-up Visit (Day 34)

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

Time frame:
Baseline and Day 34 (post Day 1 of Period 1 dosing)
Reported as:
Mean · Breaths per minute
Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)
Breaths per minute[14C]-Linerixibat 90 Milligram Oral Solution
Change From Baseline in Respiratory Rate at Follow-up Visit (Day 34)-1.7 ± 3.67
SecondaryPeriod 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.

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Degree Celsius
Period 1: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points
Degree CelsiusLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV
Day 1 (4 Hours)0.4 ± 0.37
Day 8-0.4 ± 0.63
SecondaryPeriod 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.

Time frame:
Baseline, Day 1 (4 Hours) and Day 8
Reported as:
Mean · Degree Celsius
Period 2: Change From Baseline in Tympanic Membrane Temperature at Indicated Time-points
Degree Celsius[14C]-Linerixibat 90 Milligram Oral Solution
Day 1 (4 Hours)0.2 ± 0.58
Day 8-0.4 ± 0.56
SecondaryChange From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)

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

Time frame:
Baseline and Day 34 (post Day 1 of Period 1 dosing)
Reported as:
Mean · Degree Celsius
Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)
Degree Celsius[14C]-Linerixibat 90 Milligram Oral Solution
Change From Baseline in Tympanic Membrane Temperature at Follow-up Visit (Day 34)0.3 ± 0.37

Adverse events

Collected over SAEs and non-serious AEs were collected from the start of study treatment up to Day 34.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV0/6 (0%)0/6 (0%)3/6 (50%)
[14C]-Linerixibat 90 Milligram Oral Solution0/6 (0%)0/6 (0%)3/6 (50%)
Most frequent other events
Most frequent other events
EventLinerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV[14C]-Linerixibat 90 Milligram Oral Solution
DiarrhoeaGastrointestinal disorders2/61/6
Abdominal discomfortGastrointestinal disorders1/60/6
ConstipationGastrointestinal disorders1/60/6
Back painMusculoskeletal and connective tissue disorders1/61/6
HeadacheNervous system disorders1/60/6
ErythemaSkin and subcutaneous tissue disorders0/61/6

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Mean41.2 ± 8.13
Sex: Female, Male
Sex: Female, Male(Participants)Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Female0
Male6
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Linerixibat Tab+[14C]Linerixibat IV/[14C] Linerixibat Oral Sol
Black or African American2
White - White/Caucasian/European Heritage4
08

Study locations

1 site
  • GSK Investigational Site
    London, NW10 7EW, United Kingdom
09

References and documents

Study documents

  • Study protocol · Apr 11, 2019
  • Statistical analysis plan · Jan 17, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 26, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03992014
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Jun 19, 2019
Start date
Jul 8, 2019
Primary completion
Aug 26, 2019
Completion
Aug 26, 2019
Results posted
Jun 26, 2020
Last update
Jun 26, 2020

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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