Trial Outcomes & Findings for A Phase 1 Positron Emission Tomography Study to Measure Cholesterol 24S-Hydroxylase Target Occupancy of TAK-935 (NCT NCT02497235)

Last Updated: 2017-04-11

Results Overview

CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: total volume of distribution \[VT\] (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - non-displaceable volume of distribution \[VND\]), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept. Data was reported only for TAK-935 600 mg because only first two participants were analyzed at 45 minutes post-TAK-935 dose.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

11 participants

Primary outcome timeframe

45 minutes post-TAK-935 dose

Results posted on

2017-04-11

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 01 July 2015 to 04 January 2016.

Healthy participants received up to 370 megabecquerel (MBq) (10 millicurie \[mCi\]) of \[18F\]MNI-792 with a mass of up to 5 microgram (mcg) at baseline and were enrolled to 1 of 5 treatment groups: TAK-935 50 milligram (mg), 100 mg, 200 mg, 300 mg, and 600 mg.

Participant milestones

Participant milestones
Measure	TAK-935 50 mg TAK-935 50 mg, solution, orally, once on Day 1 and up to 370 MBq (10 mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at 2 hours and 24 hours post-TAK-935 dose.	TAK-935 100 mg TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants and at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.
Overall Study STARTED	2	2	2	2	3
Overall Study COMPLETED	2	2	2	2	3
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 1 Positron Emission Tomography Study to Measure Cholesterol 24S-Hydroxylase Target Occupancy of TAK-935

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAK-935 50 mg n=2 Participants TAK-935 50 mg, solution, orally, once on Day 1 and up to 370 MBq (10 mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at 2 hours and 24 hours post-TAK-935 dose.	TAK-935 100 mg n=2 Participants TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg n=2 Participants TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg n=2 Participants TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg n=3 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants and at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.	Total n=11 Participants Total of all reporting groups
Age, Continuous	40.0 years STANDARD_DEVIATION 7.07 • n=5 Participants	25.5 years STANDARD_DEVIATION 2.12 • n=7 Participants	42.0 years STANDARD_DEVIATION 2.83 • n=5 Participants	48.5 years STANDARD_DEVIATION 2.12 • n=4 Participants	36.7 years STANDARD_DEVIATION 6.11 • n=21 Participants	38.4 years STANDARD_DEVIATION 8.48 • n=10 Participants
Sex/Gender, Customized Male	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants	11 participants n=10 Participants
Region of Enrollment United States	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants	11 participants n=10 Participants
Ethnicity Hispanic or Latino	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	4 participants n=10 Participants
Ethnicity Not Hispanic or Latino	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants	7 participants n=10 Participants
Race Black or African American	2 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	6 participants n=10 Participants
Race White	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants	5 participants n=10 Participants
Height	171.5 centimeter (cm) STANDARD_DEVIATION 4.95 • n=5 Participants	181.5 centimeter (cm) STANDARD_DEVIATION 3.54 • n=7 Participants	177.0 centimeter (cm) STANDARD_DEVIATION 4.24 • n=5 Participants	180.0 centimeter (cm) STANDARD_DEVIATION 0.00 • n=4 Participants	183.0 centimeter (cm) STANDARD_DEVIATION 16.09 • n=21 Participants	179.0 centimeter (cm) STANDARD_DEVIATION 8.69 • n=10 Participants
Weight	86.05 kilogram (kg) STANDARD_DEVIATION 7.283 • n=5 Participants	93.60 kilogram (kg) STANDARD_DEVIATION 10.748 • n=7 Participants	79.40 kilogram (kg) STANDARD_DEVIATION 12.869 • n=5 Participants	87.05 kilogram (kg) STANDARD_DEVIATION 5.162 • n=4 Participants	84.83 kilogram (kg) STANDARD_DEVIATION 23.692 • n=21 Participants	86.06 kilogram (kg) STANDARD_DEVIATION 13.009 • n=10 Participants
Body Mass Index (BMI)	29.22 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 0.789 • n=5 Participants	28.37 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.157 • n=7 Participants	25.46 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.327 • n=5 Participants	26.87 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.593 • n=4 Participants	24.95 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.275 • n=21 Participants	26.79 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.212 • n=10 Participants

PRIMARY outcome

Timeframe: 45 minutes post-TAK-935 dose

Population: PET target occupancy set where 45 minutes post-TAK-935-dose assessment were available. PET target occupancy set included all participants who received study drug (TAK-935) and had a technically adequate Baseline PET scan and at least 1 technically adequate post-TAK-935 dose PET scan.

Outcome measures

Outcome measures
Measure	TAK-935 600 mg n=2 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants.	TAK-935 100 mg TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.
Cholesterol 24S-Hydroxylase (CH24H) Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 45 Minutes Post-TAK-935 Dose Participant 1	NA percentage of occupancy Data was not reported because post dose imaging data was not quantifiable.	—	—	—	—
Cholesterol 24S-Hydroxylase (CH24H) Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 45 Minutes Post-TAK-935 Dose Participant 2	98 percentage of occupancy	—	—	—	—
Cholesterol 24S-Hydroxylase (CH24H) Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 45 Minutes Post-TAK-935 Dose Participant 3	NA percentage of occupancy Data was not reported because only two participants were analyzed at 45 minutes post-TAK-935.	—	—	—	—

PRIMARY outcome

Timeframe: 2 hours post-TAK-935 dose

Population: PET target occupancy set where 2 hour post-TAK-935-dose assessment were available. PET target occupancy set included all participants who received study drug (TAK-935) and had a technically adequate Baseline PET scan and at least 1 technically adequate post-TAK-935 dose PET scan.

CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept.

Outcome measures

Outcome measures
Measure	TAK-935 600 mg n=2 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants.	TAK-935 100 mg n=2 Participants TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg n=2 Participants TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg n=2 Participants TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg n=1 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 2 Hours Post-TAK-935 Dose Participant 1	70 percentage of occupancy	79 percentage of occupancy	96 percentage of occupancy	91 percentage of occupancy	NA percentage of occupancy Data not reported because participant was not imaged at 2 hours post-TAK-935 600 mg dose.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 2 Hours Post-TAK-935 Dose Participant 2	64 percentage of occupancy	85 percentage of occupancy	89 percentage of occupancy	89 percentage of occupancy	NA percentage of occupancy Data not reported because participant was not imaged at 2 hours post-TAK-935 600 mg dose.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 2 Hours Post-TAK-935 Dose Participant 3	NA percentage of occupancy Data was not reported because only two participants were analyzed at 2 hour post-TAK-935 dose.	NA percentage of occupancy Data was not reported because only two participants were analyzed at 2 hour post-TAK-935 dose.	NA percentage of occupancy Data was not reported because only two participants were analyzed at 2 hour post-TAK-935 dose.	NA percentage of occupancy Data was not reported because only two participants were analyzed at 2 hour post-TAK-935 dose.	96 percentage of occupancy

PRIMARY outcome

Timeframe: 10 hours post-TAK-935 dose

Population: PET target occupancy set where 10 hour post-TAK-935-dose assessment were available. PET target occupancy set included all participants who received study drug (TAK-935) and had a technically adequate Baseline PET scan and at least 1 technically adequate post-TAK-935 dose PET scan.

Outcome measures

Outcome measures
Measure	TAK-935 600 mg n=2 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants.	TAK-935 100 mg TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 10 Hours Post-TAK-935 Dose Participant 2	87 percentage of occupancy	—	—	—	—
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 10 Hours Post-TAK-935 Dose Participant 1	92 percentage of occupancy	—	—	—	—
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 10 Hours Post-TAK-935 Dose Participant 3	NA percentage of occupancy Data not reported because Participant 3 was not imaged at 10 hours post-TAK-935 600 mg dose.	—	—	—	—

PRIMARY outcome

Timeframe: 24 hours post-TAK-935 dose

Population: PET target occupancy set where 24 hour post-TAK-935-dose assessment were available. PET target occupancy set included all participants who received study drug (TAK-935) and had a technically adequate Baseline PET scan and at least 1 technically adequate post-TAK-935 dose PET scan.

Outcome measures

Outcome measures
Measure	TAK-935 600 mg n=2 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants.	TAK-935 100 mg n=2 Participants TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg n=2 Participants TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg n=2 Participants TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg n=1 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 24 Hours Post-TAK-935 Dose Participant 1	22 percentage of occupancy	13 percentage of occupancy	79 percentage of occupancy	46 percentage of occupancy	NA percentage of occupancy Data not reported because participant was not imaged at 24 hours post-TAK-935 600 mg dose.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 24 Hours Post-TAK-935 Dose Participant 2	11 percentage of occupancy	NA percentage of occupancy Data was not reported due to non-availability of blood data for second dose scan.	47 percentage of occupancy	27 percentage of occupancy	NA percentage of occupancy Data not reported because participant was not imaged at 24 hours post-TAK-935 600 mg dose.
CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 24 Hours Post-TAK-935 Dose Participant 3	NA percentage of occupancy Data was not reported because only two participants were analyzed at 24 hour post-TAK-935 dose.	NA percentage of occupancy Data was not reported because only two participants were analyzed at 24 hour post-TAK-935 dose.	NA percentage of occupancy Data was not reported because only two participants were analyzed at 24 hour post-TAK-935 dose.	NA percentage of occupancy Data was not reported because only two participants were analyzed at 24 hour post-TAK-935 dose.	52 percentage of occupancy

SECONDARY outcome

Timeframe: At time 0 (just after tracer injection), 1 hour after tracer injection and 2 hours after tracer injection for each post-TAK-935 dosing PET scan period

Population: Pharmacokinetic (PK) set included all participants who received TAK-935 and had at least 1 measurable plasma concentration for either TAK-935 or its M-1 metabolite. Data was reported for Participant 1 and 2 of each of TAK-935 50, 100, 200, and 300 mg arms and Participant 1, 2, and 3 of TAK-935 600 mg arm.

Outcome measures

Outcome measures
Measure	TAK-935 600 mg n=2 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose for the first 2 enrolled participants.	TAK-935 100 mg n=2 Participants TAK-935 100 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 200 mg n=2 Participants TAK-935 200 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 300 mg n=2 Participants TAK-935 300 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose.	TAK-935 600 mg n=3 Participants TAK-935 600 mg, solution, orally, once on Day 1 and up to 370 MBq (10mCi) of \[18F\]MNI-792 with a mass of up to 5 mcg, injection, intravenously, prior to first PET imaging at Baseline, 2 hours and 24 hours post-TAK-935 dose for the participant enrolled later.
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 3: PET Scan 2: 1 hour post-tracer dose	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	2.58 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 3:PET Scan 2: 2 hours post-tracer dose	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	2.24 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 1:PET Scan 1: 2 hours post-tracer dose	2.98 nanogram per milliliter (ng/mL)	2.45 nanogram per milliliter (ng/mL)	30.3 nanogram per milliliter (ng/mL)	12.9 nanogram per milliliter (ng/mL)	379 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 1: PET Scan 2: pre-tracer dose	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	14.2 nanogram per milliliter (ng/mL)	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	22.3 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 1:PET Scan 2: 1 hour post-tracer dose	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	9.16 nanogram per milliliter (ng/mL)	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	16 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 1:PET Scan 2:2 hours post-tracer dose	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	8.08 nanogram per milliliter (ng/mL)	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	14.4 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 2: PET Scan 1: pre-tracer dose	6.92 nanogram per milliliter (ng/mL)	23.9 nanogram per milliliter (ng/mL)	34.8 nanogram per milliliter (ng/mL)	50.9 nanogram per milliliter (ng/mL)	569 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 2: PET Scan 1: 1 hour post-tracer dose	2.97 nanogram per milliliter (ng/mL)	12.3 nanogram per milliliter (ng/mL)	16.8 nanogram per milliliter (ng/mL)	15.7 nanogram per milliliter (ng/mL)	257 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 2:PET Scan 1: 2 hours post-tracer dose	1.95 nanogram per milliliter (ng/mL)	6.46 nanogram per milliliter (ng/mL)	7.52 nanogram per milliliter (ng/mL)	14.6 nanogram per milliliter (ng/mL)	90.8 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 2: PET Scan 2: pre-tracer dose	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	1.83 nanogram per milliliter (ng/mL)	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	7.99 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 2:PET Scan 2: 1 hour post-tracer dose	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	1.28 nanogram per milliliter (ng/mL)	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	6.27 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 2:PET Scan 2:2 hours post-tracer dose	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	NA nanogram per milliliter (ng/mL) Data could not be analyzed because data was below the limit of quantitation.	5.12 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 3: PET Scan 1: pre-tracer dose	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	589 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 3: PET Scan 1: 1 hour post-tracer dose	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	236 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 3:PET Scan 1: 2 hours post-tracer dose	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	155 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 3: PET Scan 2: pre-tracer dose	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	NA nanogram per milliliter (ng/mL) Data was not reported because only two participants were enrolled in this arm.	3.04 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 1: PET Scan 1: pre-tracer dose	9.16 nanogram per milliliter (ng/mL)	11.3 nanogram per milliliter (ng/mL)	158 nanogram per milliliter (ng/mL)	56.2 nanogram per milliliter (ng/mL)	6.83 nanogram per milliliter (ng/mL)
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods Participant 1: PET Scan 1: 1 hour post-tracer dose	3.79 nanogram per milliliter (ng/mL)	5.02 nanogram per milliliter (ng/mL)	72.7 nanogram per milliliter (ng/mL)	19.4 nanogram per milliliter (ng/mL)	200 nanogram per milliliter (ng/mL)

SECONDARY outcome

Timeframe: Baseline (Day -1): 1 hour and at multiple timepoints (up to 12 hours) post check in and Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-TAK-935 dose

Population: PK set included all participants who received TAK-935 and had at least 1 measurable plasma concentration for either TAK-935 or its M-1 metabolite. Data was reported for Participant 1 and 2 of each of TAK-935 50, 100, 200, and 300 mg arms and Participant 1, 2, and 3 of TAK-935 600 mg arm.

Percent change was calculated as = \[(Postdose AUEC24(2) - Baseline AUEC24(2))/Baseline AUEC24(2)\]\*100 percent.