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 Clinical Trial

Official title:

A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04454918
• Other study ID #: TAK-906-1007
• Secondary ID: U1111-1254-4588
• Status: Completed
• Phase: Phase 1
• Start date: July 30, 2020
• Est. completion date: September 30, 2020

Study information

• Verified date: December 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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]).

Description:

The drug being tested in this study is called TAK-906. The study will determine ABA in Period 1, and ADME, and mass balance of TAK-906 after single oral administration in Period 2 in healthy adult male participants. Plasma and urine samples will be collected for PK determination; plasma, whole blood, urine, and feces samples will be collected for total radioactivity (TRA) determination; and plasma, urine, and feces samples will be collected to characterize the metabolite profiles of TAK-906.

The study will enroll approximately 6 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (ADME study period). In Period 1 (ABA study period), all participants will receive single unlabeled oral 50 mg dose of TAK-906 as capsule followed by microdose of 100 μg (approximately 1 μCi) [14C]-TAK-906 as intravenous infusion followed by a washout period of at least 7 days before the dose in Period 2. In Period 2 (ADME study period), all participants will receive a single dose of 50 mg (approximately 100 μCi) [14C]-TAK-906 as an oral solution.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including screening period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: September 30, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study.

2. 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:

1. 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.

2. Estimated creatinine clearance less than (<) 90 milliliter per minute (mL/min) at screening.

3. 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.

4. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.

5. 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]).

6. 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.

7. Donation of blood or significant blood loss within 56 days prior to the first dosing.

8. Plasma donation within 7 days prior to the first dosing.

9. 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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TAK-906 Oral Capsule
TAK-906 capsule.
• [14C]-TAK-906 Intravenous Infusion
[14C]-TAK-906 intravenous infusion.
• [14C]-TAK-906 Oral Solution
[14C]-TAK-906 oral solution.

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Period 1: Absolute Bioavailability Based on Ratio of Dose Normalized Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC8 ) for TAK-906	Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability for plasma TAK-906, calculated as geometric least squares mean ratio: [Actual Dose (IV) x AUC8 (oral)] / [Actual Dose (oral) x AUC8 (IV)] multiplied (x) 100, where AUC8 for IV infusion was normalized to a 50 mg dose.	Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Primary	Period 2: Cum%Dose (UR): Cumulative Percentage of Total Radioactivity Excreted in Urine for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose in Treatment Period 2
Primary	Period 2: Cum%Dose (FE): Cumulative Percentage of Total Radioactivity Excreted in Feces for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose in Treatment Period 2
Primary	Period 2: Combined Cum%Dose: Cumulative Combined Percent of Total Radioactivity Excreted in Urine and Feces for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose in Treatment Period 2
Secondary	Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-906 and Metabolite (M23) After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Secondary	Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
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		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Secondary	Period 1: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC8) Extrapolated for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Secondary	Period 1: t(1/2)z : Terminal Disposition Phase Half-life for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Secondary	Period 1: Vz/F: Apparent Volume of Distribution During the Terminal Elimination Phase for TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Secondary	Period 1: CL/F: Apparent Total Plasma Clearance for TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
Secondary	Period 1: Ceoi: Plasma Total Radioactivity Concentration at the End of Infusion for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: AUClast: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: AUC8: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Total Radioactivity Concentration for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: CL: Total Clearance for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: Vss: Volume of Distribution During the Terminal Disposition Phase for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC8) Extrapolated for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 1: t(1/2)z: Terminal Disposition Phase Half-life for [14C]-TAK-906		Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Secondary	Period 2: Cmax: Maximum Observed Plasma Concentration for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
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		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC8) Extrapolated for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: t(1/2)z: Terminal Disposition Phase Half-life for TAK-906 and M23 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: Vz/F: Apparent Volume of Distribution During the Terminal Elimination Phase for TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: CL/F: Apparent Total Plasma Clearance for TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: Cmax: Maximum Observed Plasma Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: Tmax: Time to Reach the Maximum Plasma Total Radioactivity Concentration (Cmax) for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
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		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
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		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: AUC8: Area Under the Plasma Total Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
Secondary	Period 2: Cmax: Maximum Observed Whole Blood Total Radioactivity Concentration for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 2
Secondary	Period 2: Tmax: Time to Reach the Maximum Whole Blood Total Radioactivity Concentration (Cmax) for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 2
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		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose in Treatment Period 2
Secondary	Period 2: AUC8: Area Under the Whole Blood Total Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-906 After Oral Administration		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 2
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		Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 2