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

NCT03500224 | Completed Phase 1 Results

• 4 other identifiers: TAK-954-1005U1111-1202-5762NL65503.056.182018-001181-42
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (30)

• 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 Outcomes (4)

• 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

Study Arms (1)

[14C]-TAK-954 0.5 mg

EXPERIMENTAL

\[14C\]-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

Interventions

[14C]-TAK-954 DRUG

\[14C\]-TAK-954 intravenous infusion.

[14C]-TAK-954 0.5 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

PRAHS

Groningen, 9728 NZ, Netherlands

Location

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

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: April 9, 2018
• First Posted: April 18, 2018
• Study Start: April 30, 2018
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: July 29, 2019
• Results First Posted: July 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)