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

NCT04234672 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-831-1008U1111-1242-9877
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (21)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (12)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg

EXPERIMENTAL

TAK-831 500 mg, tablet, orally, once on Day 1, followed by \[14C\]TAK-831 50 micrograms (μg) \[approximately 1 microcurie (μCi)\], infusion, intravenously (IV), once on Day 1 of Treatment Period 1, followed by a washout period of 8 days, further followed by \[14C\]TAK-831 500 mg (approximately 100 μCi), suspension, orally, once under fasted state on Day 1 of Treatment Period 2.

Drug: TAK-831 Oral Tablet; Drug: [14C]TAK-831 IV Infusion; Drug: [14C]TAK-831 Oral Suspension

Interventions

TAK-831 Oral Tablet DRUG

TAK-831 tablet.

Also known as: Luvadaxistat

TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg

[14C]TAK-831 IV Infusion DRUG

\[14C\]TAK-831 IV infusion.

TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg

[14C]TAK-831 Oral Suspension DRUG

\[14C\]TAK-831 oral suspension.

TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg

Eligibility Criteria

• Age: 19 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neurocrine Biosciences: lead
• Takeda: collaborator

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

Results Point of Contact

• Title: Neurocrine Medical Information
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 21, 2020
• Study Start: February 17, 2020
• Primary Completion: April 4, 2020
• Study Completion: April 4, 2020
• Last Updated: June 30, 2021
• Results First Posted: April 28, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)