Trial Outcomes & Findings for 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 (NCT NCT04992442)
NCT ID: NCT04992442
Last Updated: 2021-10-04
Results Overview
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.
COMPLETED
PHASE1
6 participants
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1
2021-10-04
Participant Flow
Participants took part in the study at 1 investigative site in the United States from 09 July 2020 to 18 August 2020.
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
Treatment Period 1
STARTED
|
6
|
|
Treatment Period 1
COMPLETED
|
6
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
|
Washout Period
STARTED
|
6
|
|
Washout Period
COMPLETED
|
6
|
|
Washout Period
NOT COMPLETED
|
0
|
|
Treatment Period 2
STARTED
|
6
|
|
Treatment Period 2
COMPLETED
|
6
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg + [14C]TAK-935 300 mg
n=6 Participants
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.
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|---|---|
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Age, Continuous
|
34.0 years
STANDARD_DEVIATION 14.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
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6 Participants
n=5 Participants
|
|
Weight
|
84.82 kg
STANDARD_DEVIATION 16.899 • n=5 Participants
|
|
Height
|
176.5 cm
STANDARD_DEVIATION 7.31 • n=5 Participants
|
|
Body Mass Index (BMI)
|
27.000 kg/m^2
STANDARD_DEVIATION 3.4142 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1Population: 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.
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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Percent Absolute Bioavailability (%F) for TAK-935
|
12.57 percent absolute bioavailability
Geometric Coefficient of Variation 75.1
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-935 Excreted in Urine and Feces Combined [Combined Cum%Dose]
|
97.55 percentage of dose
Geometric Coefficient of Variation 0.5
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u])
|
292.3 mg equivalents (eq) of parent drug
Geometric Coefficient of Variation 1.4
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f])
|
9.429 mg eq of parent drug
Geometric Coefficient of Variation 48.2
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe)
|
300.7 mg eq of parent drug
Geometric Coefficient of Variation 0.5
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u])
|
94.81 percentage of dose
Geometric Coefficient of Variation 1.4
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (Cum%Dose[f])
|
3.058 percentage of dose
Geometric Coefficient of Variation 48.2
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-935
|
1352 ng/mL
Geometric Coefficient of Variation 61.3
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-935
|
0.42 hours (hr)
Interval 0.42 to 0.42
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=5 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-935 in Plasma
|
4.374 hr
Interval 3.51 to 10.55
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=5 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935
|
1805 ng*hr/mL
Geometric Coefficient of Variation 40.4
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935
|
1547 ng*hr/mL
Geometric Coefficient of Variation 40.8
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
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
|
1638 ng*hr/mL
Geometric Coefficient of Variation 43.1
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration
|
17220 ng eq/mL
Geometric Coefficient of Variation 34.4
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
|
0.599 hr
Interval 0.43 to 0.77
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration
|
3.655 hr
Interval 2.78 to 10.82
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-inf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity
|
42890 ng eq*hr/mL
Geometric Coefficient of Variation 21.4
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-t: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Time t
|
39580 ng eq*hr/mL
Geometric Coefficient of Variation 21.6
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-last: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
|
40650 ng eq*hr/mL
Geometric Coefficient of Variation 21.9
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration
|
9157 ng eq/g
Geometric Coefficient of Variation 29.0
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)
|
0.440 hr
Interval 0.44 to 0.77
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration
|
3.678 hr
Interval 3.04 to 20.42
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-inf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity
|
24420 nanograms (ng) eq*hr/g
Geometric Coefficient of Variation 19.9
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: The data for TAK-935 concentration in whole blood were not collected therefore AUC0-t cannot be determined and not available.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: AUC0-last: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
|
22280 ng eq*hr/g
Geometric Coefficient of Variation 20.2
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
Renal clearance (CLr) is the volume of plasma entering the kidney that is completely cleared of drug per unit of time.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: CLR: Renal Clearance for TAK-935 in Urine
|
6.792 L/hr
Geometric Coefficient of Variation 21.8
|
—
|
PRIMARY outcome
Timeframe: 0-12, 12-24, 24-48, 48-72, 72-96, 96-120 hours post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Ae0-12 hours
|
268.1 mg eq
Geometric Coefficient of Variation 4.4
|
—
|
|
Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Ae12-24 hours
|
18.28 mg eq
Geometric Coefficient of Variation 35.0
|
—
|
|
Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Ae24-48 hours
|
3.829 mg eq
Geometric Coefficient of Variation 66.2
|
—
|
|
Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Ae48-72 hours
|
0.3126 mg eq
Geometric Coefficient of Variation 92.8
|
—
|
|
Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Ae72-96 hours
|
0.1946 mg eq
Geometric Coefficient of Variation 80.6
|
—
|
|
Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval
Ae96-120 hours
|
0.2296 mg eq
Geometric Coefficient of Variation NA
The geometric coefficient of variation was not estimable as only one participant had measurable amount.
|
—
|
PRIMARY outcome
Timeframe: 0.17, 0.42, 0.75, 1.5, 2.5, 4.5, 8, 12, and 24 hours post-dose in Treatment Period 2Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
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 Hour
|
0.5881 ratio
Standard Deviation 0.065712
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
0.42 Hour
|
0.5440 ratio
Standard Deviation 0.054836
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
0.75 Hour
|
0.5561 ratio
Standard Deviation 0.026316
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
1.5 Hours
|
0.5361 ratio
Standard Deviation 0.025054
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
2.5 Hours
|
0.5934 ratio
Standard Deviation 0.052200
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
4.5 Hours
|
0.5823 ratio
Standard Deviation 0.038252
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
8 Hours
|
0.5647 ratio
Standard Deviation 0.046592
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
12 Hours
|
0.6960 ratio
Standard Deviation 0.16172
|
—
|
|
Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma
24 Hours
|
1.036 ratio
Standard Deviation NA
The standard deviation was not estimable as there was only one participant.
|
—
|
SECONDARY outcome
Timeframe: Day 1: At the end of infusion (at 15 minutes post dose) in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-935
|
2472 picograms (pg) eq /mL
Geometric Coefficient of Variation 22.7
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-935 After Oral Administration
|
822.8 ng/mL
Geometric Coefficient of Variation 149.6
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-935 After Oral Administration
|
1.129 hr
Interval 0.42 to 1.54
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 After Oral Administration
|
1304 ng*hr/mL
Geometric Coefficient of Variation 69.3
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-935 After IV Administration
|
1742 pg eq*hr/mL
Geometric Coefficient of Variation 15.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to t After Oral Administration
|
1250 ng*hr/mL
Geometric Coefficient of Variation 68.6
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935 After IV Administration
|
1691 pg eq*hr/mL
Geometric Coefficient of Variation 15.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-935 After Oral Administration
|
1268 ng*hr/mL
Geometric Coefficient of Variation 70.3
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
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
|
1713 pg eq*hr/mL
Geometric Coefficient of Variation 15.3
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-935 After Oral Administration in Plasma
|
4.249 hr
Interval 2.19 to 5.95
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: t(1/2)z: Terminal Disposition Half-life for [14C]TAK-935 After IV Administration in Plasma
|
1.358 hr
Interval 0.6 to 12.46
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=5 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u]) After IV Administration
|
48.14 µg eq
Geometric Coefficient of Variation 1.4
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f]) After IV Administration
|
0.7988 µg eq
Geometric Coefficient of Variation 76.2
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=5 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe) After IV Administration
|
48.82 µg eq
Geometric Coefficient of Variation 1.4
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u]) After IV Administration
|
95.17 percentage of dose
Geometric Coefficient of Variation 1.3
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 1Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 1: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (%Dose[f]) After IV Administration
|
1.587 percentage of dose
Geometric Coefficient of Variation 76.4
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
TAK-935
|
1 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M1
|
1 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M2
|
0 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M3
|
1 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M4
|
1 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M5
|
0 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M6
|
0 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M7
|
0 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M8
|
1 sample positive
|
—
|
|
Period 2: Metabolic Profile of TAK-935 in Plasma After Oral Administration of [14C]TAK-935
M9
|
0 sample positive
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2Population: 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.
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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
n=6 Participants
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M1
|
1 sample positive
|
0 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
TAK-935
|
1 sample positive
|
1 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M2
|
1 sample positive
|
1 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M3
|
1 sample positive
|
0 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M4
|
1 sample positive
|
0 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M5
|
1 sample positive
|
0 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M6
|
1 sample positive
|
0 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M7
|
1 sample positive
|
0 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M8
|
1 sample positive
|
1 sample positive
|
|
Period 2: Metabolic Profile of TAK-935 in Urine and Feces After Oral Administration of [14C]TAK-935
M9
|
0 sample positive
|
1 sample positive
|
SECONDARY outcome
Timeframe: From first dose up to 30 days after last dose of study drug (up to approximately 40 days)Population: 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.
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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
n=6 Participants
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Percentage of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
|
0 percentage of participants
|
16.7 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose up to 30 days after last dose of study drug (up to approximately 40 days)Population: 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.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
n=6 Participants
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Electrocardiogram (ECG) Parameters
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose up to 30 days after last dose of study drug (up to approximately 40 days)Population: 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.
Vital Signs included blood pressure (systolic and diastolic), heart rate (HR), respiratory rate, and temperature.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
n=6 Participants
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Vital Sign Parameters
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From first dose up to 30 days after last dose of study drug (up to approximately 40 days)Population: 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.
The laboratory parameters included tests for serum chemistry, hematology, coagulation, and urinalysis.
Outcome measures
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 Participants
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 (Feces)
n=6 Participants
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Percentage of Participants With Treatment Emergent Clinically Relevant Changes in Laboratory Parameters
|
0 percentage of participants
|
0 percentage of participants
|
Adverse Events
TAK-935 300 mg + [14C]TAK-935 50 μg
[14C]TAK-935 300 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
TAK-935 300 mg + [14C]TAK-935 50 μg
n=6 participants at risk
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
n=6 participants at risk
\[14C\]TAK-935 300 mg (approximately 100 μCi), solution, orally, under fasted state, once on Day 1 of Treatment Period 2.
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/6 • From first dose up to 30±2 days after last dose of study drug (up to approximately 40 days)
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.
|
16.7%
1/6 • From first dose up to 30±2 days after last dose of study drug (up to approximately 40 days)
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER