Clinical trial 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2020-01-21
Enrollment: 6
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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:

1. Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at screening.
2. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
3. Estimated creatinine clearance \<80 milliliter per minute (mL/min) at screening.
4. 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.
5. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
6. 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 \[mrem\]).
7. 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.
8. Donation of blood or significant blood loss within 56 days prior to the first dosing.
9. Plasma donation within 7 days prior to the first dosing.

Primary outcomes:
measure: Period 1: Percent Absolute Bioavailability (%F) for TAK-831
timeFrame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
measure: Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose]
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe)
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR])
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe])
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
measure: Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-831
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: AUCinf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: AUClast: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: AUCinf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: AUClast: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
measure: Period 2: CLR: Renal Clearance for TAK-831 in Urine
timeFrame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Secondary outcomes:
measure: Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-831
timeFrame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
measure: Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-831 After Oral Administration
timeFrame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
measure: Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 After Oral Administration
timeFrame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
measure: Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 After Oral Administration
timeFrame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
measure: Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-831 After IV Administration
timeFrame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
measure: Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-831 After Oral Administration
timeFrame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
measure: Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-831 After IV Administration
timeFrame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
measure: Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma
timeFrame: 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
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 38 days)
measure: Number of Participants With TEAEs Related to Electrocardiogram (ECG)
timeFrame: Up to Day 14
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: Up to Day 14
measure: Number of Participants With TEAEs Related to Laboratory Parameters
timeFrame: Up to Day 14
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
References: