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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04234672
• Other study ID #: TAK-831-1008
• Secondary ID: U1111-1242-9877
• Status: Completed
• Phase: Phase 1
• Start date: February 17, 2020
• Est. completion date: April 4, 2020

Study information

• Verified date: June 2021
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 4, 2020
• Est. primary completion date: April 4, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TAK-831 Oral Tablet
TAK-831 tablet.
• [14C]TAK-831 IV Infusion
[14C]TAK-831 IV infusion.
• [14C]TAK-831 Oral Suspension
[14C]TAK-831 oral suspension.

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
Neurocrine Biosciences	Takeda

Country where clinical trial is conducted

United States, 

Outcome

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