Phase 1
N=6
Study to Assess Absolute Bioavailability (ABA) of TAK-906 and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Participants
Healthy Volunteers
Bottom Line
View on ClinicalTrials.gov: NCT04454918 ↗Enrolled (actual)
6
Serious AEs
0.0%
Results posted
Mar 2022
Primary outcome: Primary: Period 1: Absolute Bioavailability Based on Ratio of Dose Normalized Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞ ) for TAK-906 — 9.12 percent absolute bioavailability
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- TAK-906 Oral Capsule (Drug); [14C]-TAK-906 Intravenous Infusion (Drug); [14C]-TAK-906 Oral Solution (Drug)
- Age
- Adult · 19+ yrs
- Sex
- Male
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Sep 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Period 1: Absolute Bioavailability Based on Ratio of Dose Normalized Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞ ) for TAK-906 |
9.12 | — |
| PRIMARY Period 2: Cum%Dose (UR): Cumulative Percentage of Total Radioactivity Excreted in Urine for [14C]-TAK-906 |
2.162 | — |
| PRIMARY Period 2: Cum%Dose (FE): Cumulative Percentage of Total Radioactivity Excreted in Feces for [14C]-TAK-906 |
94.44 | — |
| PRIMARY Period 2: Combined Cum%Dose: Cumulative Combined Percent of Total Radioactivity Excreted in Urine and Feces for [14C]-TAK-906 |
96.65 | — |
| SECONDARY Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-906 and Metabolite (M23) After Oral Administration |
29.72; 2.293 | — |
| SECONDARY Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 and M23 After Oral Administration |
1.750; 1.750 | — |
| SECONDARY Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906 and M23 After Oral Administration |
78.62; 6.185 | — |
| SECONDARY Period 1: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) Extrapolated for TAK-906 and M23 After Oral Administration |
0.6598; 4.288 | — |
| SECONDARY Period 1: t(1/2)z : Terminal Disposition Phase Half-life for TAK-906 and M23 After Oral Administration |
3.892; 1.722 | — |
| SECONDARY Period 1: Vz/F: Apparent Volume of Distribution During the Terminal Elimination Phase for TAK-906 After Oral Administration |
3545 | — |
| SECONDARY Period 1: CL/F: Apparent Total Plasma Clearance for TAK-906 After Oral Administration |
631.3 | — |
| SECONDARY Period 1: Ceoi: Plasma Total Radioactivity Concentration at the End of Infusion for [14C]-TAK-906 |
3.529 | — |
| SECONDARY Period 1: AUClast: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-TAK-906 |
2.047 | — |
| SECONDARY Period 1: AUC∞: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-906 |
1.976 | — |
| SECONDARY Period 1: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Total Radioactivity Concentration for [14C]-TAK-906 |
10.847 | — |
| SECONDARY Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]-TAK-906 |
3795 | — |
| SECONDARY Period 1: CL: Total Clearance for [14C]-TAK-906 |
57.55 | — |
| SECONDARY Period 1: Vss: Volume of Distribution During the Terminal Disposition Phase for [14C]-TAK-906 |
33.04 | — |
| SECONDARY Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-TAK-906 |
1549 | — |
| SECONDARY Period 1: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) Extrapolated for [14C]-TAK-906 |
0.3908 | — |
| SECONDARY Period 1: t(1/2)z: Terminal Disposition Phase Half-life for [14C]-TAK-906 |
1.196 | — |
| SECONDARY Period 2: Cmax: Maximum Observed Plasma Concentration for TAK-906 and M23 After Oral Administration |
26.81; 1.086 | — |
| SECONDARY Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 and M23 After Oral Administration |
0.500; 0.999 | — |
| SECONDARY Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906 and M23 After Oral Administration |
46.54; 2.111 | — |
| SECONDARY Period 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 and M23 After Oral Administration |
49.40; 2.490 | — |
| SECONDARY Period 2: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) Extrapolated for TAK-906 and M23 After Oral Administration |
3.993; 8.013 | — |
| SECONDARY Period 2: t(1/2)z: Terminal Disposition Phase Half-life for TAK-906 and M23 After Oral Administration |
9.993; 1.833 | — |
| SECONDARY Period 2: Vz/F: Apparent Volume of Distribution During the Terminal Elimination Phase for TAK-906 After Oral Administration |
14430 | — |
| SECONDARY Period 2: CL/F: Apparent Total Plasma Clearance for TAK-906 After Oral Administration |
1007 | — |
| SECONDARY Period 2: Cmax: Maximum Observed Plasma Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration |
39.85 | — |
| SECONDARY Period 2: Tmax: Time to Reach the Maximum Plasma Total Radioactivity Concentration (Cmax) for [14C]-TAK-906 After Oral Administration |
0.758 | — |
| SECONDARY Period 2: AUCt: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Time of the Last Common Time Point t for [14C]-TAK-906 After Oral Administration |
109.0 | — |
| SECONDARY Period 2: AUClast: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-TAK-906 After Oral Administration |
135.5 | — |
| SECONDARY Period 2: AUC∞: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-906 After Oral Administration |
144.3 | — |
| SECONDARY Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration |
35.539 | — |
| SECONDARY Period 2: Cmax: Maximum Observed Whole Blood Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration |
28.41 | — |
| SECONDARY Period 2: Tmax: Time to Reach the Maximum Whole Blood Total Radioactivity Concentration (Cmax) for [14C]-TAK-906 After Oral Administration |
0.504 | — |
| SECONDARY Period 2: AUClast: Area Under the Whole Blood Total Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-TAK-906 After Oral Administration |
83.17 | — |
| SECONDARY Period 2: AUC∞: Area Under the Whole Blood Total Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-906 After Oral Administration |
87.25 | — |
| SECONDARY Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration |
16.964 | — |
Summary
The purpose of this study is to determine ABA of TAK-906 following single oral (capsule) administration of 50 milligram (mg) of TAK-906 and single intravenous (IV) microtracer dose administration of 100 microgram (μg) (approximately 1 microcurie [μCi]) of [14C]-TAK-906 in Period 1 (ABA), and to determine the mass balance of TAK-906 in urine and feces following a single oral (solution) administration of 50 mg (approximately 100 μCi) of [14C]-TAK-906 in Period 2 (absorption, distribution, metabolism, and elimination [ADME]).
Eligibility Criteria
Inclusion Criteria
- Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study.
- Body mass index (BMI) greater than or equal to (>=) 18.0 and less than (˂) 30.0 kilogram per square meter (kg/m^2) at screening.
Exclusion Criteria
- QT interval corrected for heart rate using Fridericia's formula (QTcF) interval is greater than (>) 450 millisecond (msec) or Electrocardiogram (ECG) findings are deemed abnormal with clinical significance by the Investigator or designee at screening.
- Estimated creatinine clearance less than (<) 90 milliliter per minute (mL/min) at screening.
- Has tattoo(s) or scarring at or near the site of intravenous (IV) 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 last 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.
- Unable to refrain from or anticipates the use of:
- Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Acetaminophen (up to 2 g per 24 hour period) and Milk of Magnesia® (that is, magnesium hydroxide [less than or equal to (<=) 60 mL per day after Day 3 in Period 1 and after Day 8 in Period 2]) may be permitted during the study, only after dosing, if necessary to treat adverse events (AEs). Additional administration of Milk of Magnesia® may be administered on other days at discretion of the Investigator.
- Any drugs known to significantly affect the absorption, distribution, metabolism or elimination of TAK-906 within 28 days prior to the first dosing and throughout the study. Appropriate sources (example, Flockhart Table TM) will be consulted to confirm lack of PK/pharmacodynamics interaction with study drug.
Data sourced from ClinicalTrials.gov (NCT04454918). 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.