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Completed

NCT Number: NCT03500224

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

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.

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

PRAHS

Groningen, 9728 NZ, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Be a man aged 18 to 55 years, inclusive, at the screening visit.
  • 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.
  • 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.
  • 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

  • Has total 14C radioactivity measured by accelerator mass spectrometry in plasma (during screening) exceeding 14C/12C ratio 1.1E-12.
  • 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.
  • 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.
  • Irregular defecation pattern (less than once per 2 days).
  • 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).
  • 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.
  • Has a substance abuse disorder.

Treatment and study plan

[14C]-TAK-954

Drug

[14C]-TAK-954 intravenous infusion.

Primary outcomes

  1. Cumulative Percentage of Administered Radioactivity Recovered in Urine

    Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose

  2. Cumulative Percentage of Administered Radioactivity Recovered in Feces

    Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose

  3. Cumulative Percentage of Radioactivity in Urine and Feces Combined

    Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose

  4. Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

    Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.

  5. Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

    Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.

  6. Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

    Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.

  7. Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  8. Cumulative Percentage of Dose Excreted in Urine for TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose

  9. Cumulative Percentage of Dose Excreted in Feces for TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

    The cumulative percentage of dose excreted in feces as TAK-954 derived from 0-168 hour sampling was normalized for 100% recovery.

  10. Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  11. Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  12. Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  13. 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

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  14. 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

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  15. AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  16. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  17. Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  18. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  19. t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  20. t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  21. CL: Total Clearance After Intravenous Administration for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  22. CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  23. Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  24. Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  25. Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  26. Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  27. Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  28. Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  29. Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  30. Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

Secondary outcomes

  1. Ratio of Total Radioactivity in Whole Blood to Plasma

    Time frame: Day 1 pre-dose and at multiple time points (up to 264 hours) post-dose

  2. 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

    Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose

  3. Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE)

    Time frame: Baseline up to Day 31

  4. Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of [14C]-TAK-954

    Time frame: Baseline up to Day 15

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Apr 18, 2018
Registry last updated
Jul 29, 2019

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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