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Completed

NCT Number: NCT04234672

A Study to Assess Absolute Bioavailability (ABA) of TAK-831 and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of [14C]TAK-831 in Male Healthy Participants

The purpose of this study is to determine ABA of TAK-831 following a single microdose intravenous administration of 50 microgram (μg) (approximately 1 microcurie [μCi]) [14C]TAK-831 and a single oral administration of 500 milligram (mg) TAK-831 tablets in Period 1, and to assess the mass balance, characterize the PK of TAK-831 in plasma and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral suspension dose of 500 mg (approximately 100 μCi) [14C]TAK-831 in Period 2.

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Key information

Conditions

Age range

19 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Celerion

Lincoln, Nebraska, 68502, United States

About this study

The drug being tested in this study is called TAK-831 (also known as luvadaxistat). The study will determine ABA in Period 1, and the absorption, metabolism, excretion, and mass balance of TAK-831 after single oral administration in Period 2 in healthy adult male participants, by collecting plasma, urine, and feces samples for drug concentration analysis, and plasma, whole blood, urine, and fecal samples for total radioactivity analysis and metabolic profiling.

The study will enroll approximately 6 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (absorption, distribution, metabolism, and elimination [ADME] study period). In Period 1 (ABA study period), all participants will receive a single unlabelled oral dose of TAK-831 as tablet and a microdose intravenous infusion of 50 μg (approximately 1 μCi) [14C]TAK-831, followed by a washout period of 8 days before the dose in Period 2. In Period 2 (ADME study period), all participants will receive a single dose of 500 mg (approximately 100 μCi) [14C]TAK-831 as an oral suspension.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including screening period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Weighs at least 45 kilogram (kg) and body mass index (BMI) greater than or equal to (>=) 18.0 and less than (˂) 32.0 kilogram per square meter (kg/m^2) at screening.

Exclusion criteria

  • Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at screening.
  • Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
  • Estimated creatinine clearance <80 milliliter per minute (mL/min) at screening.
  • Has tattoo(s) or scarring at or near the site of intravenous infusion or any other condition which may interfere with infusion site examination, in the opinion of the Investigator.
  • Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
  • Has received radiolabeled substances or has been exposed to radiation sources within 12 months of first dosing or is likely to receive radiation exposure or radioisotopes within 12 months of first dosing such that participation in this study would increase their total exposure beyond the recommended levels considered safe (that is weighted annual limit recommended by the International Commission on Radiological Protection [ICRP] of 3000 milli roentgen equivalent man [mrem]).
  • Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study.
  • Donation of blood or significant blood loss within 56 days prior to the first dosing.
  • Plasma donation within 7 days prior to the first dosing.

Treatment and study plan

TAK-831 Oral Tablet

Drug

TAK-831 tablet.

Other names: Luvadaxistat

[14C]TAK-831 IV Infusion

Drug

[14C]TAK-831 IV infusion.

[14C]TAK-831 Oral Suspension

Drug

[14C]TAK-831 oral suspension.

Primary outcomes

  1. Period 1: Percent Absolute Bioavailability (%F) for TAK-831

    Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1

    Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability, calculated for plasma TAK-831 as [Actual Dose (IV) x AUCinf (oral)] / [Actual Dose (oral) x AUCinf (IV)] x 100.

  2. Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose]

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  3. Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe)

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  4. Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR])

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  5. Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe])

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  6. Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

  7. Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  8. Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  9. Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  10. Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-831

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  11. Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  12. Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  13. Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  14. Period 2: AUCinf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  15. Period 2: AUClast: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  16. Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  17. Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  18. Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  19. Period 2: AUCinf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  20. Period 2: AUClast: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2

  21. Period 2: CLR: Renal Clearance for TAK-831 in Urine

    Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Secondary outcomes

  1. Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-831

    Time frame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1

  2. Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-831 After Oral Administration

    Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1

  3. Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 After Oral Administration

    Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1

  4. Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 After Oral Administration

    Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1

  5. Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-831 After IV Administration

    Time frame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1

  6. Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-831 After Oral Administration

    Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1

  7. Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-831 After IV Administration

    Time frame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1

  8. Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma

    Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours for TAK-831 and up to 95 hours for [14C]TAK-831) post-dose

  9. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

    Time frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 38 days)

    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug.

  10. Number of Participants With TEAEs Related to Electrocardiogram (ECG)

    Time frame: Up to Day 14

    The ECG parameters were considered TEAEs if they were judged to be clinically significant (i.e., if some action or intervention was required or if the Investigator judged the change to be beyond the range of normal physiologic fluctuation).

  11. Number of Participants With TEAEs Related to Vital Signs

    Time frame: Up to Day 14

    Vital Signs included body temperature, respiratory rate, blood pressure, and heart rate. Any clinically significant changes from Baseline as assessed by the investigator were reported as TEAEs.

  12. Number of Participants With TEAEs Related to Laboratory Parameters

    Time frame: Up to Day 14

    The laboratory parameters included parameters of hematology, serum checmistry and urinalysis. The laboratory parameters were considered TEAEs if their values were judged to be clinically significant (i.e., if some action or intervention was required or if the Investigator judged the change to be beyond the range of normal).

Sponsors and collaborators

Lead sponsor

Neurocrine Biosciences

Industry

Collaborators

  • Takeda

Registry information

Official study title

A Phase 1 Study to Assess Absolute Bioavailability of TAK-831 and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]TAK-831 in Male Healthy Subjects

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Jan 21, 2020
Registry last updated
Jun 30, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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