A Study to Evaluate the Mass Balance, Pharmacokinetics (PK), Metabolism and Excretion of TAK-954 Containing Microtracer ([14C]-TAK-954) in Healthy Male Participants

A Phase 1, Open-label, Single Intravenous Infusion Dose Study to Evaluate the Mass Balance, Pharmacokinetics, Metabolism, and Excretion of TAK-954 Containing Microtracer ([14C]-TAK-954) in Healthy Adult Male Subjects

The purpose of this study is to determine the mass balance, routes of elimination and characterize the metabolic profiles of a single intravenous dose of [14C]-TAK-954, identify major circulating and excreted metabolites. This study will also determine the single-dose PK of total radioactivity, TAK-954 and its metabolites where possible.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [14C]-TAK-954

Detailed Description

The drug being tested in this study is called TAK-954. This study will assess the mass balance, metabolic profiles and routes of elimination of single intravenous dose of [14C]-TAK-954, and will determine the major circulating and excreted metabolites and single-dose PK of total radioactivity, TAK-954, THRX513466, and THRX 913682 in healthy male participants.

The study will enroll approximately 6 participants. All participants will receive a single dose of [14C]-TAK-954 0.5 mg on Day 1.

This single-center trial will be conducted in Netherlands. The overall time to participate in this study is approximately 6 to 7 weeks. Participants will make a final visit to the clinic 15 days after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRAHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Be a man aged 18 to 55 years, inclusive, at the screening visit.
2. Have a body mass index (BMI) greater than or equal to (>=) 18 and less than or equal to (<=) 30 kilogram per square meter (kg/m^2) and a body weight greater than (>) 50 kilogram (kg) at the screening visit.
3. Be a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the initial dose of trial drug.

4. Meet the following birth control requirements:

   • Is a male participant who is sterile or agrees to use an appropriate method of contraception, including a condom, from the first dose of study drug until 30 days after the last dose of study drug. No restrictions are required for a vasectomized male participant provided that the participant is at least 1 year postbilateral vasectomy procedure before the first dose of study drug. A male participant whose vasectomy procedure was performed less than 1 year before the first dose of study drug must follow the same restrictions as a nonvasectomized man. Appropriate documentation of surgical procedures should be provided.
   • Is a male participant who agrees to not donate sperm from trial drug administration on the first day of the first dose until 30 days after the last dose of study drug.

Exclusion Criteria:

1. Has total 14C radioactivity measured by accelerator mass spectrometry in plasma (during screening) exceeding 14C/12C ratio 1.1E-12.
2. Participated in any study with a radiation dose above 0.1 millibecquerel (MBq) or radiation burden above 0.1 millisievert (mSv) within 1 year before screening.
3. Was exposed to significant radiation (example, serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months before check-in.
4. Irregular defecation pattern (less than once per 2 days).
5. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to beer 354 milliliter [mL]/12 ounce [oz], wine 118 mL/4 oz, or distilled spirits 29.5 mL/1 oz).
6. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
7. Has a substance abuse disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]-TAK-954 0.5 mg; [14C]-TAK-954 0.5 milligram (mg), (containing approximately 1.5 microcurie [µCi] of radioactive tracer), administered as 60-minute infusion, intravenously, once on Day 1.	Drug: [14C]-TAK-954; [14C]-TAK-954 intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Percentage of Administered Radioactivity Recovered in Urine		Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Cumulative Percentage of Administered Radioactivity Recovered in Feces		Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Cumulative Percentage of Radioactivity in Urine and Feces Combined		Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined	Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.	Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine	Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.	Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces	Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.	Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Cumulative Percentage of Dose Excreted in Urine for TAK-954		Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Cumulative Percentage of Dose Excreted in Feces for TAK-954	The cumulative percentage of dose excreted in feces as TAK-954 derived from 0-168 hour sampling was normalized for 100% recovery.	Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 and TAK-954 Metabolites		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
CL: Total Clearance After Intravenous Administration for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954		Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Ratio of Total Radioactivity in Whole Blood to Plasma	Day 1 pre-dose and at multiple time points (up to 264 hours) post-dose
Ratio of AUC∞: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 to Total Radioactivity in Plasma TAK-954	Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE)	Baseline up to Day 31
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of [14C]-TAK-954	Baseline up to Day 15

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2018
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (Actual): April 18, 2018

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: May 31, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Drug therapy
• Other Study ID Numbers: TAK-954-1005; U1111-1202-5762 (Other Identifier: WHO); NL65503.056.18 (Registry Identifier: NL); 2018-001181-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No