Phase 1
N=6
A Study to Evaluate the Mass Balance, Pharmacokinetics (PK), Metabolism and Excretion of TAK-954 Containing Microtracer ([14C]-TAK-954) in Healthy Male Participants
Healthy Volunteers
Bottom Line
View on ClinicalTrials.gov: NCT03500224 ↗Enrolled (actual)
6
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcome: Primary: Cumulative Percentage of Administered Radioactivity Recovered in Urine — 55.4; 56.8; 55.1 percentage of radioactive dose
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- [14C]-TAK-954 (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cumulative Percentage of Administered Radioactivity Recovered in Urine |
55.4; 56.8; 55.1 | — |
| PRIMARY Cumulative Percentage of Administered Radioactivity Recovered in Feces |
28.8; 30.3; 30.0 | — |
| PRIMARY Cumulative Percentage of Radioactivity in Urine and Feces Combined |
84.1; 87.0; 85.1 | — |
| PRIMARY Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined |
3.0; 13.6; 4.3; 5.0; 1.6; 0.5 | — |
| PRIMARY Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine |
3.0; 4.8; 4.3; 1.6; 0.8; 0.6 | — |
| PRIMARY Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces |
8.8; 3.4; 0.8; 0.5; 0.5; 13.7 | — |
| PRIMARY Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites |
74.28 | — |
| PRIMARY Cumulative Percentage of Dose Excreted in Urine for TAK-954 |
31.33; 29.73; 27.35 | — |
| PRIMARY Cumulative Percentage of Dose Excreted in Feces for TAK-954 |
13.7 | — |
| PRIMARY Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 |
NA; 5.15; 5.87; 2.88; 2.40; 2.05 | — |
| PRIMARY Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954 |
6.28; 5.78 | — |
| PRIMARY Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites |
5.91; 0.0143 | — |
| PRIMARY 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 |
83.6; 75.4 | — |
| PRIMARY 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 |
55.4; 0.0371 | — |
| PRIMARY AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954 |
87.2; 79.0 | — |
| PRIMARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites |
55.7 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954 |
1.00; 1.00 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites |
1.00; 1.00 | — |
| PRIMARY t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954 |
70.0; 46.4 | — |
| PRIMARY t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites |
34.3 | — |
| PRIMARY CL: Total Clearance After Intravenous Administration for [14C]-TAK-954 |
— | — |
| PRIMARY CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954 |
8.97 | — |
| PRIMARY Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for [14C]-TAK-954 |
— | — |
| PRIMARY Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 |
444 | — |
| PRIMARY Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954 |
278 | — |
| PRIMARY Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954 |
157 | — |
| PRIMARY Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954 |
144 | — |
| PRIMARY Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954 |
31.3 | — |
| PRIMARY Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954 |
55.6 | — |
| PRIMARY Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954 |
28.8 | — |
| SECONDARY Ratio of Total Radioactivity in Whole Blood to Plasma |
0.92; 0.93; 0.94; 0.94; 0.92; 0.96 | — |
| SECONDARY 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 |
0.642 | — |
| SECONDARY Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) |
50.0 | — |
| SECONDARY Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of [14C]-TAK-954 |
0.0 | — |
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.
Eligibility Criteria
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 ( ) 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.
Data sourced from ClinicalTrials.gov (NCT03500224). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.