Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to determine ABA of TAK-831 following a single microdose intravenous administration of 50 microgram (μg) (approximately 1 microcurie \[μCi\]) \[14C\]TAK-831 and a single oral administration of 500 milligram (mg) TAK-831 tablets in Period 1, and to assess the mass balance, characterize the PK of TAK-831 in plasma and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral suspension dose of 500 mg (approximately 100 μCi) \[14C\]TAK-831 in Period 2.
Detailed description
The drug being tested in this study is called TAK-831 (also known as luvadaxistat). The study will determine ABA in Period 1, and the absorption, metabolism, excretion, and mass balance of TAK-831 after single oral administration in 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 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (absorption, distribution, metabolism, and elimination \[ADME\] study period). In Period 1 (ABA study period), all participants will receive a single unlabelled oral dose of TAK-831 as tablet and a microdose intravenous infusion of 50 μg (approximately 1 μCi) \[14C\]TAK-831, followed by a washout period of 8 days before the dose in Period 2. In Period 2 (ADME study period), all participants will receive a single dose of 500 mg (approximately 100 μCi) \[14C\]TAK-831 as an oral suspension. 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.
Interventions
DRUGTAK-831 Oral Tablet
TAK-831 tablet.
DRUG[14C]TAK-831 IV Infusion
\[14C\]TAK-831 IV infusion.
DRUG[14C]TAK-831 Oral Suspension
\[14C\]TAK-831 oral suspension.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Weighs at least 45 kilogram (kg) and body mass index (BMI) greater than or equal to (\>=) 18.0 and less than (˂) 32.0 kilogram per square meter (kg/m\^2) at screening.
Exclusion criteria
1. Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at screening. 2. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening. 3. Estimated creatinine clearance \<80 milliliter per minute (mL/min) at screening. 4. Has tattoo(s) or scarring at or near the site of intravenous infusion or any other condition which may interfere with infusion site examination, in the opinion of the Investigator. 5. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing. 6. 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 (that is weighted annual limit recommended by the International Commission on Radiological Protection \[ICRP\] of 3000 milli roentgen equivalent man \[mrem\]). 7. 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. 8. Donation of blood or significant blood loss within 56 days prior to the first dosing. 9. Plasma donation within 7 days prior to the first dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period 2: CLR: Renal Clearance for TAK-831 in Urine | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose | — |
| Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831 | Day 1 pre-dose and at multiple time points (up to 240 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 of TAK-831 | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| 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 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: AUCinf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: AUClast: 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 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax) | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| 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 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: AUCinf: 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 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: AUClast: 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 240 hours) post-dose in Treatment Period 2 | — |
| Period 1: Percent Absolute Bioavailability (%F) for TAK-831 | Day 1 pre-dose and at multiple time points (up to 96.5 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-831 as \[Actual Dose (IV) x AUCinf (oral)\] / \[Actual Dose (oral) x AUCinf (IV)\] x 100. |
| Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose] | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe) | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR]) | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe]) | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831 | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose | — |
| Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831 | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
| Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma | Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-831 After Oral Administration | Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1 | — |
| Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 After Oral Administration | Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1 | — |
| Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 After Oral Administration | Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1 | — |
| Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-831 After IV Administration | 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 TAK-831 After Oral Administration | Day 1 pre-dose and at multiple time points (up to 96.5 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-831 After IV Administration | 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 Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma | Day 1 pre-dose and at multiple time points (up to 96.5 hours for TAK-831 and up to 95 hours for [14C]TAK-831) post-dose | — |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to 30 days after last dose of study drug (up to approximately 38 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 with an onset that occurs after receiving study drug. |
| Number of Participants With TEAEs Related to Electrocardiogram (ECG) | Up to Day 14 | The ECG parameters were considered TEAEs if they were judged to be clinically significant (i.e., if some action or intervention was required or if the Investigator judged the change to be beyond the range of normal physiologic fluctuation). |
| Number of Participants With TEAEs Related to Vital Signs | Up to Day 14 | Vital Signs included body temperature, respiratory rate, blood pressure, and heart rate. Any clinically significant changes from Baseline as assessed by the investigator were reported as TEAEs. |
| Number of Participants With TEAEs Related to Laboratory Parameters | Up to Day 14 | The laboratory parameters included parameters of hematology, serum checmistry and urinalysis. The laboratory parameters were considered TEAEs if their values were judged to be clinically significant (i.e., if some action or intervention was required or if the Investigator judged the change to be beyond the range of normal). |
| Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-831 | Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1 | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 17 Feb 2020 to 04 April 2020.
Pre-assignment details
Healthy male participants were enrolled in this study to receive TAK-831 tablets followed by radio-labelled TAK-831 intravenous (IV) infusion on Day 1 of Treatment Period 1 and radio-labelled TAK-831 oral suspension on Day 1 of Treatment Period 2. There was an 8-day washout period between the two periods.
Participants by arm
| Arm | Count |
|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg TAK-831 5 X 100 mg tablets, orally, once on Day 1, followed by \[14C\]TAK-831 50 micrograms (μg) \[approximately 1 microcurie (μCi)\], infusion, intravenously (IV), once on Day 1 of Treatment Period 1, followed by a washout period of 8 days, further followed by \[14C\]TAK-831 500 mg (approximately 100 μCi), suspension, orally, once under fasted state on Day 1 of Treatment Period 2. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg |
|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 6.9 |
| Body Mass Index (BMI) | 26.28 kg/m^2 STANDARD_DEVIATION 1.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 174.8 cm STANDARD_DEVIATION 6.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
| Weight | 80.25 kg STANDARD_DEVIATION 6.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Period 1: Percent Absolute Bioavailability (%F) for TAK-831
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-831 as \[Actual Dose (IV) x AUCinf (oral)\] / \[Actual Dose (oral) x AUCinf (IV)\] x 100.
Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of TAK-831 5 X 100 mg tablets and 50 ug IV dose in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: Percent Absolute Bioavailability (%F) for TAK-831 | 17.34 percent absolute bioavailability | Geometric Coefficient of Variation 31.3 |
Primary
Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831 | 4198 ng*hr/mL | Geometric Coefficient of Variation 30.8 |
Primary
Period 2: AUCinf: 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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: AUCinf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity | 31010 ng eq*hr/mL | Geometric Coefficient of Variation 9.8 |
Primary
Period 2: AUCinf: 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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: AUCinf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity | 15180 ng eq*hr/g | Geometric Coefficient of Variation 13.7 |
Primary
Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-831 | 4171 ng*hr/mL | Geometric Coefficient of Variation 30.8 |
Primary
Period 2: AUClast: 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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: AUClast: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration | 28860 ng eq*hr/mL | Geometric Coefficient of Variation 8.8 |
Primary
Period 2: AUClast: 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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: AUClast: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration | 13420 ng eq*hr/g | Geometric Coefficient of Variation 14.2 |
Primary
Period 2: CLR: Renal Clearance for TAK-831 in Urine
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: CLR: Renal Clearance for TAK-831 in Urine | 0.06547 L/hr | Geometric Coefficient of Variation 38.6 |
Primary
Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831 | 1243 ng/mL | Geometric Coefficient of Variation 33.2 |
Primary
Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration | 5878 ng eq/mL | Geometric Coefficient of Variation 11.4 |
Primary
Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration | 2881 ng eq/g | Geometric Coefficient of Variation 9.2 |
Primary
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe])
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe]) | 60.71 percentage of dose | Geometric Coefficient of Variation 5.9 |
Primary
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR])
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR]) | 27.50 percentage of dose | Geometric Coefficient of Variation 19.8 |
Primary
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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration | 3.162 hr | Standard Deviation 0.3068 |
Primary
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma | 10.314 hr | Standard Deviation 6.39 |
Primary
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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration | 2.580 hr | Standard Deviation 0.3922 |
Primary
Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831 | 0.799 hours (hr) |
Primary
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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) | 2.005 hr |
Primary
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 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax) | 2.001 hr |
Primary
Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe)
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe) | 472.7 mg equivalents (eq) of parent drug | Geometric Coefficient of Variation 3.3 |
Primary
Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose]
Time frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of \[14C\]TAK-831 500 mg oral suspension in Treatment Period 2 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose] | 88.66 percentage of dose | Geometric Coefficient of Variation 3.6 |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
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 with an onset that occurs after receiving study drug.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (up to approximately 38 days)
Population: Safety Population included all participants who received at least one dose of the study drug. Data is reported as per the treatment received in Treatment Periods 1 and 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| [14C]TAK-831 50 μg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| [14C]TAK-831 500 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Number of Participants With TEAEs Related to Electrocardiogram (ECG)
The ECG parameters were considered TEAEs if they were judged to be clinically significant (i.e., if some action or intervention was required or if the Investigator judged the change to be beyond the range of normal physiologic fluctuation).
Time frame: Up to Day 14
Population: Safety Population included all participants who received at least one dose of the study drug and will be included in the safety evaluations. Data is reported as per the treatment received in Treatment Periods 1 and 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| [14C]TAK-831 50 μg | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| [14C]TAK-831 500 mg | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Laboratory Parameters
The laboratory parameters included parameters of hematology, serum checmistry and urinalysis. The laboratory parameters were considered TEAEs if their values were judged to be clinically significant (i.e., if some action or intervention was required or if the Investigator judged the change to be beyond the range of normal).
Time frame: Up to Day 14
Population: Safety Population included all participants who received at least one dose of the study drug and will be included in the safety evaluations. Data is reported as per the treatment received in Treatment Periods 1 and 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Number of Participants With TEAEs Related to Laboratory Parameters | 0 Participants |
| [14C]TAK-831 50 μg | Number of Participants With TEAEs Related to Laboratory Parameters | 0 Participants |
| [14C]TAK-831 500 mg | Number of Participants With TEAEs Related to Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Vital Signs
Vital Signs included body temperature, respiratory rate, blood pressure, and heart rate. Any clinically significant changes from Baseline as assessed by the investigator were reported as TEAEs.
Time frame: Up to Day 14
Population: Safety Population included all participants who received at least one dose of the study drug and will be included in the safety evaluations. Data is reported as per the treatment received in Treatment Periods 1 and 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| [14C]TAK-831 50 μg | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| [14C]TAK-831 500 mg | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
Secondary
Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-831 After IV Administration
Time frame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the \[14C\]TAK-831 50 ug IV dose in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-831 After IV Administration | 1992 pg*hr/mL | Geometric Coefficient of Variation 18.1 |
Secondary
Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 After Oral Administration
Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of TAK-831 5 X 100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 After Oral Administration | 3436 nanogram hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 45.7 |
Secondary
Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-831 After IV Administration
Time frame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the \[14C\]TAK-831 50 ug IV dose in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-831 After IV Administration | 1972 pg*hr/mL | Geometric Coefficient of Variation 18.1 |
Secondary
Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-831 After Oral Administration
Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of TAK-831 5 X 100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-831 After Oral Administration | 3397 ng*hr/mL | Geometric Coefficient of Variation 46.6 |
Secondary
Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the \[14C\]TAK-831 50 μg IV infusion in Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-831 | 2903 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 26.7 |
Secondary
Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-831 After Oral Administration
Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of TAK-831 5 X 100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-831 After Oral Administration | 1121 ng/mL | Geometric Coefficient of Variation 45.5 |
Secondary
Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma
Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours for TAK-831 and up to 95 hours for [14C]TAK-831) post-dose
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of TAK-831 5 X 100 mg tablets and \[14C\]TAK-831 50 ug IV dose in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma | 12.278 hr | Standard Deviation 6.0291 |
| [14C]TAK-831 50 μg | Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma | 3.815 hr | Standard Deviation 1.0456 |
Secondary
Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 After Oral Administration
Time frame: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
Population: PK-evaluable population included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Participants who received the oral dose of TAK-831 5 X 100 mg tablets in Treatment Period 1 were evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-831 500 mg + [14C]TAK-831 50 μg | Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 After Oral Administration | 1.255 hr |