Study to Assess Absolute Bioavailability of TAK-935 (OV935) and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]TAK-935 (OV935) in Healthy Male Participants

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04992442
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 1.3
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine absolute bioavailability (ABA) of TAK-935 (F) following a single microdose intravenous (IV) administration of 50 microgram (μg) (approximately 1 microcurie [μCi]) [14C]TAK-935 and a single oral administration of 3×100 mg milligram (mg) TAK-935 tablets in Treatment Period 1, and to assess the mass balance, characterize the pharmacokinetics (PK) of TAK-935 and metabolite [M-I (N-oxide)] in plasma and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral administration of 300 mg (approximately 100 μCi) [14C]TAK-935 in Treatment Period 2.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-935 Oral Tablet; Drug: [14C]TAK-935 IV Infusion; Drug: [14C]TAK-935 Oral Solution	Phase 1

Detailed Description

The drug being tested in this study is called TAK-935 (also known as soticlestat/OV935). The study determines ABA in Treatment Period 1, and the absorption, metabolism, excretion, and mass balance of TAK-935 after single oral administration in Treatment Period 2 in healthy adult male participants, by collecting plasma, urine, and feces samples for drug concentration analysis, and plasma, whole blood, urine, and fecal samples for total radioactivity analysis and metabolic profiling.

The study will enroll approximately 6 healthy adult male participants. The study is designed to consist of 2 periods: Treatment Period 1 (ABA Study Period) and Treatment Period 2 (Absorption, Distribution, Metabolism, and Elimination [ADME] Study Period). In Treatment Period 1, all participants will receive a single unlabelled oral dose of TAK-935 as 3×100 mg tablets and a microdose IV infusion of 50 μg (approximately 1 μCi) [14C]TAK-935, followed by a Washout Period of 7 days before the dose in Treatment Period 2. In Treatment Period 2, all participants will receive a single dose of 300 mg (approximately 100 μCi) [14C]TAK-935 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. This compound was transferred to Takeda and acquired on 29 March 2021. This registration is retrospective due to the transfer of ownership.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1 Study to Assess Absolute Bioavailability of TAK-935 (OV935) and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]TAK-935 (OV935) in Healthy Adult Male Participants
• Actual Study Start Date: Jul 9, 2020
• Actual Primary Completion Date: Aug 18, 2020
• Actual Study Completion Date: Aug 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-935 300 mg + [14C]TAK-935 50 μg + [14C]TAK-935 300 mg TAK-935 3×100 mg, tablets, orally, once on Day 1, followed by [14C]TAK-935 50 micrograms (μg) [approximately 1 μCi], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by [14C]TAK-935 300 mg (approximately 100 μCi) solution, orally, once on Day 1 of Treatment Period 2.	Drug: TAK-935 Oral Tablet; TAK-935 tablet; Other Names: OV935 Soticlestat ; Drug: [14C]TAK-935 IV Infusion; [14C]TAK-935 IV infusion; Other Names: OV935 ; Drug: [14C]TAK-935 Oral Solution; [14C]TAK-935 oral solution; Other Names: OV935

Outcome Measures

Primary Outcome Measures

1. Period 1: Percent Absolute Bioavailability (%F) for TAK-935 [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1]

   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, calculated for plasma TAK-935 as [Actual Dose (IV) x Area Under the Concentration-time Curve from Time 0 to Infinity {AUCinf} (oral)] / [Actual Dose (oral) x AUCinf (IV)] x 100.

2. Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-935 Excreted in Urine and Feces Combined [Combined Cum%Dose] [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

3. Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u]) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

4. Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f]) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

5. Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

6. Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u]) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

7. Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (Cum%Dose[f]) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

8. Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

9. Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

10. Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-935 in Plasma [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

11. Period 2: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

12. Period 2: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

13. Period 2: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

14. Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

15. Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

16. Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

17. Period 2: AUC0-inf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

18. Period 2: AUC0-t: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Time t [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

19. Period 2: AUC0-last: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

20. Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

21. Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax) [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

22. Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

23. Period 2: AUC0-inf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

24. Period 2: AUC0-t: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to t [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

25. Period 2: AUC0-last: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

26. Period 2: CLR: Renal Clearance for TAK-935 in Urine [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

    Renal clearance (CLr) is the volume of plasma entering the kidney that is completely cleared of drug per unit of time.

27. Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval [0-12, 12-24, 24-48, 48-72, 72-96, 96-120 hours post-dose in Treatment Period 2]

28. Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma [0.17, 0.42, 0.75, 1.5, 2.5, 4.5, 8, 12, and 24 hours post-dose in Treatment Period 2]

Secondary Outcome Measures

1. Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-935 [Day 1: At the end of infusion (at 15 minutes post dose) in Treatment Period 1]

2. Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-935 After Oral Administration [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1]

3. Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-935 After Oral Administration [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1]

4. Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 After Oral Administration [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1]

5. Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-935 After IV Administration [Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1]

6. Period 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to t After Oral Administration [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1]

7. Period 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935 After IV Administration [Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1]

8. Period 1: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-935 After Oral Administration [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1]

9. Period 1: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-935 After IV Administration [Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1]

10. Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-935 After Oral Administration in Plasma [Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose]

11. Period 1: t(1/2)z: Terminal Disposition Half-life for [14C]TAK-935 After IV Administration in Plasma [Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose]

12. Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u]) After IV Administration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1]

13. Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f]) After IV Administration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1]

14. Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe) After IV Administration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1]

15. Period 1: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u]) After IV Administration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1]

16. Period 1: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (%Dose[f]) After IV Administration [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1]

17. Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

    The metabolic profile of TAK-935 after oral administration of [14C]TAK-935 was done to assess the presence of TAK-935 and various metabolites (M1 to M9) in plasma in at least one sample using radiometric detection and/or liquid chromatography mass spectroscopy (LCMS). The presence of any metabolite is indicated as '1' and absence is indicated as '0'. Only categories with value '1' are reported.

18. Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935 [Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2]

    The metabolic profile of TAK-935 after oral administration of [14C]TAK-935 was done to assess the presence of TAK-935 and various metabolites (M1 to M9) in urine and feces in at least one sample using radiometric detection and/or LCMS. The presence of any metabolite is indicated as '1' and absence is indicated as '0'. Data is reported separately for urine and feces.

19. Percentage of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) [From first dose up to 30 days after last dose of study drug (up to approximately 40 days)]

    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE that is starting or worsening at the time of or after study drug administration.

20. Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Electrocardiogram (ECG) Parameters [From first dose up to 30 days after last dose of study drug (up to approximately 40 days)]

21. Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Vital Sign Parameters [From first dose up to 30 days after last dose of study drug (up to approximately 40 days)]

    Vital Signs included blood pressure (systolic and diastolic), heart rate (HR), respiratory rate, and temperature.

22. Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Laboratory Parameters [From first dose up to 30 days after last dose of study drug (up to approximately 40 days)]

    The laboratory parameters included tests for serum chemistry, hematology, coagulation, and urinalysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Weighs at least 50 kg and body mass index (BMI) ≥18.0 and ˂32.0 kg/m^2 at Screening Visit.

2. Continuous nonsmoker who has not used nicotine-containing products (including vaping) for at least 3 months prior to the first dosing and throughout the study, based on participant self-reporting.

3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee.

Exclusion Criteria:

1. History or presence of cataracts or other clinically significant vision disturbances.

2. Abnormal and clinically significant ECG abnormality at Screening visit:

• QT interval with Fridericia's correction method (QTcF) >450 milliseconds (ms) confirmed with one repeat testing.

1. History or presence of gastritis, gastrointestinal tract, gastric bypass surgery, or hepatic disorder or other clinical condition which, in the opinion of the Investigator or designee, may affect the absorption, distribution, metabolism, or elimination of study drug.

2. Has a risk of suicide according to the Investigator's clinical judgment [e.g., per Columbia-Suicide Severity Rating Scale (C-SSRS)] or has made a suicide attempt in the previous year prior to Screening Visit.

3. Positive urine drug or alcohol results at screening or first check-in.

4. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or novel coronavirus 2019 (COVID-19).

5. Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at Screening.

6. Seated HR is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening Visit.

7. Estimated creatinine clearance <80 mL/min at Screening Visit.

8. Has tattoo(s) or scarring at or near the site of IV infusion or any other condition which may interfere with infusion site examination, in the opinion of the Investigator.

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

10. Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks prior to first dosing.

11. 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 first dosing such that participation in this study would increase their total exposure beyond the recommended levels considered safe [i.e., weighted annual limit recommended by the International Commission on Radiological Protection (ICRP) of 3000 milli roentgen equivalent man (mrem)].

12. Unable to refrain from or anticipates the use of:

13. Any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study, including the Follow-up Period. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration. After the first dose of study drug, ibuprofen (up to 1.2 g per 24 hours) may be administered at the discretion of the Investigator or designee. Milk of Magnesia (i.e., magnesium hydroxide) (≤60 mL per day) may be administered to ensure defecation, at discretion of the Investigator or designee.

14. Any drugs known to be significant inducers of cytochrome P450 (CYP)3A4, CYP2C19 or uridine diphosphate glucuronosyltransferase (UGT), including St. John's Wort, within 28 days prior to the first dosing and throughout the study, including the Follow-up Period. Appropriate sources (e.g., Flockhart Table^TM) will be consulted to confirm lack of PK/pharmacodynamic interaction with study drug(s).

15. Alcohol

16. 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.

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Lincoln	Nebraska	United States	68502

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jun 4, 2020
• Statistical Analysis Plan - Sep 16, 2020

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT04992442
• Other Study ID Numbers: TAK-935-1008
• First Posted: Aug 5, 2021
• Last Update Posted: Oct 4, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug Therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 09 July 2020 to 18 August 2020.
Pre-assignment Detail	Healthy male participants were enrolled in this study to receive TAK-935 tablets followed by radio-labelled TAK-935 intravenous (IV) infusion on Day 1 of Treatment Period 1 and radio-labelled TAK-935 oral solution on Day 1 of Treatment Period 2. There was a 7-day Washout Period between the two periods.

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg + [14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg, tablets, orally, once on Day 1, followed by [14C]TAK-935 50 micrograms (μg) [approximately 1 μCi], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by [14C]TAK-935 300 mg (approximately 100 μCi) solution, orally, once on Day 1 of Treatment Period 2.
Period Title: Treatment Period 1
STARTED	6
COMPLETED	6
NOT COMPLETED	0
Period Title: Treatment Period 1
STARTED	6
COMPLETED	6
NOT COMPLETED	0
Period Title: Treatment Period 1
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg + [14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg, tablets, orally, once on Day 1, followed by [14C]TAK-935 50 μg [approximately 1 μCi], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by [14C]TAK-935 300 mg (approximately 100 μCi) solution, orally, once on Day 1 of Treatment Period 2.
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.0 (14.81)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 33.3%
White	4 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	84.82 (16.899)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	176.5 (7.31)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.000 (3.4142)

Outcome Measures

1. Primary Outcome

Title	Period 1: Percent Absolute Bioavailability (%F) for TAK-935
Description	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, calculated for plasma TAK-935 as [Actual Dose (IV) x Area Under the Concentration-time Curve from Time 0 to Infinity {AUCinf} (oral)] / [Actual Dose (oral) x AUCinf (IV)] x 100.
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets and 50 μg IV dose in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, followed by [14C]TAK-935 50 μg (approximately 1 μCi), 15-minute IV infusion, once on Day 1 of Treatment Period 1.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percent absolute bioavailability]	12.57 (75.1)

2. Primary Outcome

Title	Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-935 Excreted in Urine and Feces Combined [Combined Cum%Dose]
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]	97.55 (0.5)

3. Primary Outcome

Title	Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u])
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

Analysis Population Description: PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [mg equivalents (eq) of parent drug]	292.3 (1.4)

4. Primary Outcome

Title	Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f])
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [mg eq of parent drug]	9.429 (48.2)

5. Primary Outcome

Title	Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe)
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [mg eq of parent drug]	300.7 (0.5)

6. Primary Outcome

Title	Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u])
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]	94.81 (1.4)

7. Primary Outcome

Title	Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (Cum%Dose[f])
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]	3.058 (48.2)

8. Primary Outcome

Title	Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-935
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1352 (61.3)

9. Primary Outcome

Title	Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-935
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Median (Full Range) [hours (hr)]	0.42

10. Primary Outcome

Title	Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-935 in Plasma
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure. Overall number analyzed is the number of participants with data available for analysis.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	5
Median (Full Range) [hr]	4.374

11. Primary Outcome

Title	Period 2: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure. Overall number analyzed is the number of participants with data available for analysis.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1805 (40.4)

12. Primary Outcome

Title	Period 2: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1547 (40.8)

13. Primary Outcome

Title	Period 2: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-935
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1638 (43.1)

14. Primary Outcome

Title	Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng eq/mL]	17220 (34.4)

15. Primary Outcome

Title	Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Median (Inter-Quartile Range) [hr]	0.599

16. Primary Outcome

Title	Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Median (Full Range) [hr]	3.655

17. Primary Outcome

Title	Period 2: AUC0-inf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng eq*hr/mL]	42890 (21.4)

18. Primary Outcome

Title	Period 2: AUC0-t: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Time t
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng eq*hr/mL]	39580 (21.6)

19. Primary Outcome

Title	Period 2: AUC0-last: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng eq*hr/mL]	40650 (21.9)

20. Primary Outcome

Title	Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng eq/g]	9157 (29.0)

21. Primary Outcome

Title	Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Median (Full Range) [hr]	0.440

22. Primary Outcome

Title	Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Median (Full Range) [hr]	3.678

23. Primary Outcome

Title	Period 2: AUC0-inf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanograms (ng) eq*hr/g]	24420 (19.9)

24. Primary Outcome

Title	Period 2: AUC0-t: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to t
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

The data for TAK-935 concentration in whole blood were not collected therefore AUC0-t cannot be determined and not available.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	0

25. Primary Outcome

Title	Period 2: AUC0-last: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng eq*hr/g]	22280 (20.2)

26. Primary Outcome

Title	Period 2: CLR: Renal Clearance for TAK-935 in Urine
Description	Renal clearance (CLr) is the volume of plasma entering the kidney that is completely cleared of drug per unit of time.
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	6.792 (21.8)

27. Primary Outcome

Title	Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Time Frame	0-12, 12-24, 24-48, 48-72, 72-96, 96-120 hours post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2, with data available for analysis at the given timepoint were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
Ae0-12 hours	268.1 (4.4)
Ae12-24 hours	18.28 (35.0)
Ae24-48 hours	3.829 (66.2)
Ae48-72 hours	0.3126 (92.8)
Ae72-96 hours	0.1946 (80.6)
Ae96-120 hours	0.2296 (NA)

28. Primary Outcome

Title	Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
Time Frame	0.17, 0.42, 0.75, 1.5, 2.5, 4.5, 8, 12, and 24 hours post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure. Number analyzed are the number of participants with data available for analysis at the given timepoint.

Arm/Group Title	[14C]TAK-935 300 mg
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
0.17 Hour	0.5881 (0.065712)
0.42 Hour	0.5440 (0.054836)
0.75 Hour	0.5561 (0.026316)
1.5 Hours	0.5361 (0.025054)
2.5 Hours	0.5934 (0.052200)
4.5 Hours	0.5823 (0.038252)
8 Hours	0.5647 (0.046592)
12 Hours	0.6960 (0.16172)
24 Hours	1.036 (NA)

29. Secondary Outcome

Title	Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-935
Time Frame	Day 1: At the end of infusion (at 15 minutes post dose) in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [picograms (pg) eq /mL]	2472 (22.7)

30. Secondary Outcome

Title	Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-935 After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, once on Day 1 of Treatment Period 1.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	822.8 (149.6)

31. Secondary Outcome

Title	Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-935 After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, once on Day 1 of Treatment Period 1.
Measure Participants	6
Median (Full Range) [hr]	1.129

32. Secondary Outcome

Title	Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, once on Day 1 of Treatment Period 1.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1304 (69.3)

33. Secondary Outcome

Title	Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-935 After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [pg eq*hr/mL]	1742 (15.1)

34. Secondary Outcome

Title	Period 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to t After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, once on Day 1 of Treatment Period 1.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1250 (68.6)

35. Secondary Outcome

Title	Period 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935 After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [pg eq*hr/mL]	1691 (15.1)

36. Secondary Outcome

Title	Period 1: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-935 After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, once on Day 1 of Treatment Period 1.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1268 (70.3)

37. Secondary Outcome

Title	Period 1: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-935 After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [pg eq*hr/mL]	1713 (15.3)

38. Secondary Outcome

Title	Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-935 After Oral Administration in Plasma
Time Frame	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-935 3×100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, once on Day 1 of Treatment Period 1.
Measure Participants	6
Median (Full Range) [hr]	4.249

39. Secondary Outcome

Title	Period 1: t(1/2)z: Terminal Disposition Half-life for [14C]TAK-935 After IV Administration in Plasma
Time Frame	Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Median (Full Range) [hr]	1.358

40. Secondary Outcome

Title	Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u]) After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure. Overall number analyzed is the number of participants with data available for analysis.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [µg eq]	48.14 (1.4)

41. Secondary Outcome

Title	Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f]) After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [µg eq]	0.7988 (76.2)

42. Secondary Outcome

Title	Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe) After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure. Overall number analyzed is the number of participants with data available for analysis.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [µg eq]	48.82 (1.4)

43. Secondary Outcome

Title	Period 1: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u]) After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]	95.17 (1.3)

44. Secondary Outcome

Title	Period 1: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (%Dose[f]) After IV Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received [14C]TAK-935 50 μg IV infusion in Treatment Period 1 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 50 μg
Arm/Group Description	[14C]TAK-935 50 μg (approximately 1 μCi), infusion, 15-minute IV infusion, once on Day 1 of Treatment Period 1 after the TAK-935 oral dose, followed by a Washout Period of at least 7 days.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of dose]	1.587 (76.4)

45. Secondary Outcome

Title	Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
Description	The metabolic profile of TAK-935 after oral administration of [14C]TAK-935 was done to assess the presence of TAK-935 and various metabolites (M1 to M9) in plasma in at least one sample using radiometric detection and/or liquid chromatography mass spectroscopy (LCMS). The presence of any metabolite is indicated as '1' and absence is indicated as '0'. Only categories with value '1' are reported.
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg (Plasma)
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6
TAK-935	1
M1	1
M2	0
M3	1
M4	1
M5	0
M6	0
M7	0
M8	1
M9	0

46. Secondary Outcome

Title	Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
Description	The metabolic profile of TAK-935 after oral administration of [14C]TAK-935 was done to assess the presence of TAK-935 and various metabolites (M1 to M9) in urine and feces in at least one sample using radiometric detection and/or LCMS. The presence of any metabolite is indicated as '1' and absence is indicated as '0'. Data is reported separately for urine and feces.
Time Frame	Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Outcome Measure Data

Analysis Population Description

PK Population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the dose of [14C]TAK-935 300 mg oral solution in Treatment Period 2 were evaluated for this outcome measure.

Arm/Group Title	[14C]TAK-935 300 mg (Urine)	[14C]TAK-935 300 mg (Feces)
Arm/Group Description	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6	6
TAK-935	1	1
M1	1	0
M2	1	1
M3	1	0
M4	1	0
M5	1	0
M6	1	0
M7	1	0
M8	1	1
M9	0	1

47. Secondary Outcome

Title	Percentage of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
Description	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE that is starting or worsening at the time of or after study drug administration.
Time Frame	From first dose up to 30 days after last dose of study drug (up to approximately 40 days)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of the study drug. As prespecified in the protocol data for adverse events was collected and reported for Period 1 and Period 2.

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg	[14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, followed by [14C]TAK-935 50 μg (approximately 1 μCi), 15-minute IV infusion, once on Day 1 of Treatment Period 1.	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6	6
Number [percentage of participants]	0 0%	16.7 NaN

48. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Electrocardiogram (ECG) Parameters
Time Frame	From first dose up to 30 days after last dose of study drug (up to approximately 40 days)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of the study drug. As prespecified in the protocol data for this outcome measure was collected and reported for Period 1 and Period 2.

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg	[14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, followed by [14C]TAK-935 50 μg (approximately 1 μCi), 15-minute IV infusion, once on Day 1 of Treatment Period 1.	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6	6
Number [percentage of participants]	0 0%	0 NaN

49. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Vital Sign Parameters
Description	Vital Signs included blood pressure (systolic and diastolic), heart rate (HR), respiratory rate, and temperature.
Time Frame	From first dose up to 30 days after last dose of study drug (up to approximately 40 days)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of the study drug. As prespecified in the protocol data for this outcome measure was collected and reported for Period 1 and Period 2.

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg	[14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, followed by [14C]TAK-935 50 μg (approximately 1 μCi), 15-minute IV infusion, once on Day 1 of Treatment Period 1.	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6	6
Number [percentage of participants]	0 0%	0 NaN

50. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Laboratory Parameters
Description	The laboratory parameters included tests for serum chemistry, hematology, coagulation, and urinalysis.
Time Frame	From first dose up to 30 days after last dose of study drug (up to approximately 40 days)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of the study drug. As prespecified in the protocol data for this outcome measure was collected and reported for Period 1 and Period 2.

Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg	[14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, followed by [14C]TAK-935 50 μg (approximately 1 μCi), 15-minute IV infusion, once on Day 1 of Treatment Period 1.	[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
Measure Participants	6	6
Number [percentage of participants]	0 0%	0 NaN

Adverse Events

Time Frame	From first dose up to 30±2 days after last dose of study drug (up to approximately 40 days)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory/exam findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population included all participants who received at least one dose of the study drug. As prespecified in the protocol data for adverse events was collected and reported for Period 1 and Period 2.
Arm/Group Title	TAK-935 300 mg + [14C]TAK-935 50 μg		[14C]TAK-935 300 mg
Arm/Group Description	TAK-935 3×100 mg tablets, orally, followed by [14C]TAK-935 50 μg (approximately 1 μCi), 15-minute IV infusion, once on Day 1 of Treatment Period 1.		[14C]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
All Cause Mortality
	TAK-935 300 mg + [14C]TAK-935 50 μg		[14C]TAK-935 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	TAK-935 300 mg + [14C]TAK-935 50 μg		[14C]TAK-935 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	TAK-935 300 mg + [14C]TAK-935 50 μg		[14C]TAK-935 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/6 (16.7%)
Nervous system disorders
Headache	0/6 (0%)		1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.