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

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

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]).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-906 Oral Capsule; Drug: [14C]-TAK-906 Intravenous Infusion; Drug: [14C]-TAK-906 Oral Solution

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: TAK-906 50 mg + [14C]-TAK-906 100 mcg + [14C]-TAK-906 50 mg; TAK-906 50 mg, capsule, orally, once on Day 1, followed by [14C]-TAK-906 100 micrograms (μg) [approximately 1 microcurie (μCi)], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by [14C]-TAK-906 50 mg (approximately 100 μCi), solution, orally, once on Day 1 of Treatment Period 2.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 AUC∞ (oral)] / [Actual Dose (oral) x AUC∞ (IV)] multiplied (x) 100, where AUC∞ 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
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
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
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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
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	Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1
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
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
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
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
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
Period 1: AUC∞: 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
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
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
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
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
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
Period 1: AUC%Extrap: Percent of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) Extrapolated for [14C]-TAK-906	Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
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
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
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
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
Period 2: AUC∞: 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
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	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2
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
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
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
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
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
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
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
Period 2: AUC∞: 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
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
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
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
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
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	Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 2
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

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 30, 2020
• Primary Completion (ACTUAL): September 30, 2020
• Study Completion (ACTUAL): September 30, 2020

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (ACTUAL): July 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-906-1007; U1111-1254-4588 (OTHER: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No