Phase 1 TAK-925 Study in Healthy Adult and Elderly Volunteers and Participants With Narcolepsy

A Phase 1 Study of TAK-925 to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of TAK-925 in Healthy Adult and Elderly Volunteers and Patients With Narcolepsy

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03332784

Enrollment

Registered

2017-11-06

Start date

2017-11-04

Completion date

2018-09-04

Last updated

2021-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Participants and Patients With Narcolepsy

Brief summary

The purpose of this study is to investigate safety, tolerability, and pharmacokinetics of TAK-925 when a single dose of TAK-925 is administered to healthy adult participants, healthy elderly participants and patients with type 1 narcolepsy.

Detailed description

Orexins are neuropeptides that play a role in the regulation of sleep and wakefulness. In type 1 narcolepsy, there is a loss of orexin producing neurons in the brain. The investigational drug, TAK-925, is an orexin 2 receptor agonist that is being tested in healthy adult participants, healthy elderly participants and patients with narcolepsy in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single intravenous administration. The study will enroll approximately 20 healthy participants and 16 healthy elderly participants in Part 1 of the study and approximately 20 patients with narcolepsy in Part 2. In Part 1, the study consists of 4 cohorts of 8 or 4 participants each. Participants will be randomly assigned (by chance, like flipping a coin) to one of the following treatment groups to receive TAK-925 or placebo: \- Part 1, Cohort 1; TAK-925 (Dose Level 1, 3, 5), Cohort 2; TAK-925 (Dose Level 2, 4, 6), Cohort 3 and 4; TAK-925 (Dose Level 5) For Cohort 1-4, healthy adult and elderly participants will be administered TAK-925 or placebo once in each cohort or dose level. The dose at the start (Cohort 1 dose level 1) is 7 mg of TAK-925 and following doses in Cohorts 1-4 will be determined based on available data from previous Cohorts/dose levels. In Part 2 of the study, the study consists of 3 cohorts of 4 to 12 patients with narcolepsy. Patients will be randomly assigned to one of the treatment groups of Cohort 5-7 and will be administered TAK-925 or placebo once in each cohort. The dose of TAK-925 in Cohort 5-7 is TBD and will be decided based on available data from Part 1 and previous Cohorts. \- Part 2, Cohort 5-7 This multi-center trial will be conducted in Japan. Participants will make multiple visits to the clinic. Visits in Part 1 will include a screening period (Day -28 to -2), Check-in on Day -1, Treatment period (Day 1 and 2), and follow-up visit on Day 7. In Part 2 of the study, the visits include a screening period (Day -42 to -2), Check-in on Day -1, Cross-over period (Day 1 to 4), and follow-up visit on Day 7.

Interventions

DRUGTAK-925

TAK-925 Intravenous Infusion

DRUGPlacebo

TAK-925 Placebo Intravenous Infusion

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

OTHER

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Yes

Inclusion criteria

Healthy adult participants and Healthy elderly participants: \- Participant weighs at least 50 kilogram (kg) (Healthy adults participants) / 40 kg (Healthy elderly participants) and has a body mass index (BMI) from 18.5 to 30 kilogram per square meter (kg/m\^2), inclusive at Screening. Narcolepsy patients: * Patient weighs at least 40 kg inclusive at Screening. * A diagnosis of narcolepsy Type 1, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3). * HLA narcolepsy test positivity. * At Day -1, Epworth sleepiness scale (ESS) score greater than or equal to (\>=) 10 * Blood pressure less than (\<) 140 systolic and \< 90 diastolic. The patient may have a history of hypertension and be on antihypertensive medication treatment as long as the BP meets these criteria.

Exclusion criteria

All Participants: * Participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit. * Past or current epilepsy, convulsion, tremor or the disorders of related symptoms. * Has a lifetime history of major psychiatric disorder, such as major depressive disorder, bipolar disorder, or schizophrenia. HV (only Cohort 4): \- Participant has had CSF collection performed within 14 days prior to check-in (Day -1). Narcolepsy patients * Medical disorder associated with excessive sleepiness other than narcolepsy (including sleep apnea syndrome). * Excessive caffeine (greater than \[\>\] 400 milligram per day \[mg/day\]) use one week prior to study.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Baseline up to Day 7	—
Number of Participants Who Experience at Least One TEAE Related to Vital Signs	Baseline up to Day 7	—
Number of Participants Who Experience at Least One TEAE Related to Body Weight	Baseline up to Day 7	—
Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	Baseline up to Day 7	—
Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	Baseline up to Day 7	—
Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion	—
Part 2, CL: Total Clearance After Intravenous Administration for TAK-925	Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion	—
Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion	Urine assessments were done only in Part 1, as planned.
Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion	Urine assessments were done only in Part 1, as planned.
Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion	Urine assessments were done only in Part 1, as planned.
Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4	Day 1 at 6 hours after start of infusion	—

Secondary

Measure	Time frame	Description
Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT)	Days 1 and 3 up to 8 hours following the start of infusion	The MWT is a validated objective measure that evaluates a person's ability to remain awake under soporific conditions for a defined period of time. This tendency to fall asleep is measured via electroencephalography-derived sleep latency. Sleep onset is defined as the first epoch of greater than 15 seconds of cumulative sleep in a 30-second epoch. Trials were ended after 40 minutes if no sleep occurs, or after unequivocal sleep, defined as 3 consecutive epochs of stage 1 sleep, or 1 epoch of any other stage of sleep. If no sleep has been observed according to these rules, then the latency is defined as 40 minutes. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicating greater ability to stay awake.

Countries

Japan

Participant flow

Recruitment details

Participants took part in the study at 3 investigative sites in Japan from 04 November 2017 to 04 September 2018.

Pre-assignment details

Healthy adult and elderly participants were enrolled to receive TAK-925 or placebo in Cohorts 1 and 2 under alternating panel design and in Cohorts S1, S2, 3, and 4 under parallel design of Part 1, and participants with type 1 narcolepsy were enrolled to receive TAK-925 or placebo in a 2-period cross-over design in Cohorts 5, 6, and 7 of Part 2.

Participants by arm

Arm	Count
Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + TAK-925 112 mg TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group A in double-blind, alternating panel.	2
Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + Placebo TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group B in double-blind, alternating panel.	2
Part 1 Cohort 1: TAK-925 7 mg + Placebo + TAK-925 112 mg TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg, infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group C in double-blind, alternating panel.	2
Part 1 Cohort 1: Placebo + TAK-925 28 mg + TAK-925 112 mg TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg, infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg, infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group D in double-blind, alternating panel.	2
Part 1 Cohort 2:TAK-925 14 mg +TAK-925 56 mg +TAK-925 134.4 mg TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group E in double-blind, alternating panel.	2
Part 1 Cohort 2: TAK-925 14 mg + TAK-925 56 mg + Placebo TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 3 in Group F in healthy adults in double-blind, alternating panel.	2
Part 1 Cohort 2: TAK-925 14 mg + Placebo + TAK-925 134.4 mg TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group G in double-blind, alternating panel.	2
Part 1 Cohort 2: Placebo + TAK-925 56 mg + TAK-925 134.4 mg TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group H in double-blind, alternating panel.	2
Part 1 Cohort S1-S2: Pooled Placebo TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group.	4
Part 1: Cohort S1 TAK-925 180 mg TAK-925 180 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy adults in double-blind, parallel group.	6
Part 1: Cohort S2 TAK-925 240 mg TAK-925 240 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy adults in double-blind, parallel group.	6
Part 1: Cohort 3 Placebo TAK-925 placebo-matching infusion, intravenously, once, over 9 hours on Day 1 in healthy elderly participants in double-blind, parallel group.	2
Part 1: Cohort 3 TAK-925 112 mg TAK-925 112 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy elderly participants in double-blind, parallel group.	6
Part 1: Cohort 4 TAK-925 112 mg TAK-925 112 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy adults in unblinded manner.	4
Part 2 Cohort 5: TAK-925 44.8 mg + Placebo TAK-925 44.8 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group I under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications.	2
Part 2 Cohort 5, Part J: TAK-925 Placebo + 44.8 mg TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 44.8 mg, infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group J under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications.	2
Part 2 Cohort 6: TAK-925 11.2 mg + Placebo TAK-925 11.2 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group K under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications.	2
Part 2 Cohort 6: Placebo + TAK-925 11.2 mg TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 11.2 mg, infusion, intravenously, once on Day 1 Period 2 (Day 3) in participants with type 1 narcolepsy in Group L under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications.	2
Part 2 Cohort 7: TAK-925 5 mg + Placebo TAK-925 5 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group M under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications.	3
Part 2 Cohort 7: Placebo + TAK-925 5 mg TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 5 mg, infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group N under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications	3
Total	58

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014	FG015	FG016	FG017	FG018	FG019
Parts 1 and 2 - Period 1 (1 Day)	Adverse Event	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0

Baseline characteristics

Characteristic	Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + Placebo	Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + TAK-925 112 mg	Total	Part 2 Cohort 7: Placebo + TAK-925 5 mg	Part 2 Cohort 7: TAK-925 5 mg + Placebo	Part 2 Cohort 6: Placebo + TAK-925 11.2 mg	Part 2 Cohort 6: TAK-925 11.2 mg + Placebo	Part 2 Cohort 5, Part J: TAK-925 Placebo + 44.8 mg	Part 2 Cohort 5: TAK-925 44.8 mg + Placebo	Part 1: Cohort 4 TAK-925 112 mg	Part 1: Cohort 3 TAK-925 112 mg	Part 1: Cohort 3 Placebo	Part 1: Cohort S2 TAK-925 240 mg	Part 1: Cohort S1 TAK-925 180 mg	Part 1 Cohort S1-S2: Pooled Placebo	Part 1 Cohort 2: Placebo + TAK-925 56 mg + TAK-925 134.4 mg	Part 1 Cohort 2: TAK-925 14 mg + Placebo + TAK-925 134.4 mg	Part 1 Cohort 2: TAK-925 14 mg + TAK-925 56 mg + Placebo	Part 1 Cohort 2:TAK-925 14 mg +TAK-925 56 mg +TAK-925 134.4 mg	Part 1 Cohort 1: Placebo + TAK-925 28 mg + TAK-925 112 mg	Part 1 Cohort 1: TAK-925 7 mg + Placebo + TAK-925 112 mg
Age, Continuous	25.5 years STANDARD_DEVIATION 4.95	29.0 years STANDARD_DEVIATION 5.66	33.7 years STANDARD_DEVIATION 16.26	33.7 years STANDARD_DEVIATION 4.51	42.3 years STANDARD_DEVIATION 20.11	38.5 years STANDARD_DEVIATION 0.71	25.5 years STANDARD_DEVIATION 7.78	33.0 years STANDARD_DEVIATION 15.56	21.5 years STANDARD_DEVIATION 4.95	21.3 years STANDARD_DEVIATION 0.5	67.7 years STANDARD_DEVIATION 2.94	72.5 years STANDARD_DEVIATION 3.54	27.5 years STANDARD_DEVIATION 6.72	24.5 years STANDARD_DEVIATION 5.75	24.8 years STANDARD_DEVIATION 4.57	34.5 years STANDARD_DEVIATION 4.95	28.5 years STANDARD_DEVIATION 9.19	28.0 years STANDARD_DEVIATION 9.9	24.5 years STANDARD_DEVIATION 3.54	30.0 years STANDARD_DEVIATION 4.24	22.0 years STANDARD_DEVIATION 2.83
Alcohol Classification A Few Times Per Month	0 Participants	1 Participants	25 Participants	0 Participants	2 Participants	0 Participants	1 Participants	1 Participants	1 Participants	3 Participants	2 Participants	0 Participants	4 Participants	3 Participants	4 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Alcohol Classification A Few Times Per Week	1 Participants	1 Participants	10 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Alcohol Classification Daily	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Alcohol Classification Non-alcoholic	1 Participants	0 Participants	22 Participants	2 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	1 Participants	3 Participants	1 Participants	2 Participants	3 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Body Mass Index (BMI)	22.35 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 0.919	22.25 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.475	23.19 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 4.072	29.57 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 5.689	26.10 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 7.146	26.45 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 8.697	23.60 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 0.707	24.60 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.546	32.30 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 10.041	22.03 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.791	23.22 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 3.451	23.00 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.263	21.05 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.325	20.48 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 0.768	22.65 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.912	22.15 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.626	23.40 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.687	20.90 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 0.424	21.55 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.616	22.10 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 0.141	20.85 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.899
Caffeine Classification Had caffeine consumption	0 Participants	2 Participants	35 Participants	3 Participants	1 Participants	2 Participants	2 Participants	2 Participants	2 Participants	3 Participants	5 Participants	1 Participants	3 Participants	3 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Caffeine Classification Had no caffeine consumption	2 Participants	0 Participants	23 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	3 Participants	3 Participants	3 Participants	1 Participants	1 Participants	1 Participants	2 Participants	0 Participants	2 Participants
Height	167.0 centimeter (cm) STANDARD_DEVIATION 2.83	176.0 centimeter (cm) STANDARD_DEVIATION 1.41	168.1 centimeter (cm) STANDARD_DEVIATION 8.11	168.3 centimeter (cm) STANDARD_DEVIATION 11.55	160.7 centimeter (cm) STANDARD_DEVIATION 4.73	159.5 centimeter (cm) STANDARD_DEVIATION 2.12	171.0 centimeter (cm) STANDARD_DEVIATION 1.41	174.5 centimeter (cm) STANDARD_DEVIATION 6.36	155.5 centimeter (cm) STANDARD_DEVIATION 0.71	171.0 centimeter (cm) STANDARD_DEVIATION 5.89	159.5 centimeter (cm) STANDARD_DEVIATION 4.64	149.0 centimeter (cm) STANDARD_DEVIATION 0	168.8 centimeter (cm) STANDARD_DEVIATION 5	173.0 centimeter (cm) STANDARD_DEVIATION 3.16	173.5 centimeter (cm) STANDARD_DEVIATION 5.8	171.5 centimeter (cm) STANDARD_DEVIATION 6.36	170.0 centimeter (cm) STANDARD_DEVIATION 9.9	173.0 centimeter (cm) STANDARD_DEVIATION 1.41	170.0 centimeter (cm) STANDARD_DEVIATION 4.24	177.0 centimeter (cm) STANDARD_DEVIATION 8.49	174.5 centimeter (cm) STANDARD_DEVIATION 2.12
Race and Ethnicity Not Collected	—	—	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Region of Enrollment Japan	2 Participants	2 Participants	58 Participants	3 Participants	3 Participants	2 Participants	2 Participants	2 Participants	2 Participants	4 Participants	6 Participants	2 Participants	6 Participants	6 Participants	4 Participants	2 Participants	2 Participants	2 Participants	2 Participants	2 Participants	2 Participants
Sex: Female, Male Female	0 Participants	0 Participants	12 Participants	1 Participants	3 Participants	2 Participants	0 Participants	0 Participants	2 Participants	0 Participants	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	2 Participants	2 Participants	46 Participants	2 Participants	0 Participants	0 Participants	2 Participants	2 Participants	0 Participants	4 Participants	3 Participants	1 Participants	6 Participants	6 Participants	4 Participants	2 Participants	2 Participants	2 Participants	2 Participants	2 Participants	2 Participants
Smoking Classification Current smoker	0 Participants	0 Participants	3 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Smoking Classification Former smoker	0 Participants	0 Participants	11 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Smoking Classification Non-smoker	2 Participants	2 Participants	44 Participants	1 Participants	2 Participants	1 Participants	1 Participants	1 Participants	2 Participants	3 Participants	6 Participants	2 Participants	5 Participants	5 Participants	2 Participants	1 Participants	2 Participants	1 Participants	1 Participants	2 Participants	2 Participants
Weight	62.65 kilogram (kg) STANDARD_DEVIATION 0.636	68.15 kilogram (kg) STANDARD_DEVIATION 7.707	65.20 kilogram (kg) STANDARD_DEVIATION 10.994	83.43 kilogram (kg) STANDARD_DEVIATION 15.97	67.57 kilogram (kg) STANDARD_DEVIATION 22.212	67.70 kilogram (kg) STANDARD_DEVIATION 23.9	69.05 kilogram (kg) STANDARD_DEVIATION 1.202	74.95 kilogram (kg) STANDARD_DEVIATION 0.071	78.45 kilogram (kg) STANDARD_DEVIATION 24.112	63.88 kilogram (kg) STANDARD_DEVIATION 7.029	58.77 kilogram (kg) STANDARD_DEVIATION 10.388	51.30 kilogram (kg) STANDARD_DEVIATION 4.101	59.55 kilogram (kg) STANDARD_DEVIATION 6.142	61.12 kilogram (kg) STANDARD_DEVIATION 2.86	68.73 kilogram (kg) STANDARD_DEVIATION 1.941	63.85 kilogram (kg) STANDARD_DEVIATION 8.839	68.80 kilogram (kg) STANDARD_DEVIATION 14.849	62.45 kilogram (kg) STANDARD_DEVIATION 1.909	60.95 kilogram (kg) STANDARD_DEVIATION 5.445	69.60 kilogram (kg) STANDARD_DEVIATION 6.93	62.90 kilogram (kg) STANDARD_DEVIATION 10.607

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 6	0 / 6	0 / 5	0 / 6	0 / 6	0 / 6	0 / 4	0 / 6	0 / 6	0 / 2	0 / 6	0 / 4	0 / 13	0 / 4	0 / 4	0 / 6
other Total, other adverse events	1 / 11	1 / 6	1 / 6	1 / 5	1 / 6	1 / 6	2 / 6	1 / 4	3 / 6	5 / 6	0 / 2	3 / 6	1 / 4	0 / 13	4 / 4	1 / 4	0 / 6
serious Total, serious adverse events	0 / 11	0 / 6	0 / 6	0 / 5	0 / 6	0 / 6	0 / 6	0 / 4	0 / 6	0 / 6	0 / 2	0 / 6	0 / 4	0 / 13	0 / 4	0 / 4	0 / 6

Outcome results

Primary

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

Time frame: Baseline up to Day 7

Population: The safety analysis set was defined as all participants who received at least one dose of study drug.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1 Cohort 1-2: Pooled Placebo	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 1 Cohort 1: TAK-925 7 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 1 Cohort 2: TAK-925 14 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 1 Cohort 1: TAK-925 28 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Par 1 Cohort 2: TAK-925 56 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 1 Cohort 1: TAK-925 112 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 1 Cohort 2: TAK-925 134.4 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	2 Participants
Part 1 Cohort S1-S2: Pooled Placebo	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 1 Cohort S1: TAK-925 180 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	3 Participants
Part 1 Cohort S2: TAK-925 240 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	5 Participants
Part 1 Cohort 3: Placebo	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	0 Participants
Part 1 Cohort 3: TAK-925 112 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	3 Participants
Part 1 Cohort 4: TAK-925 112 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 2 Cohort 5-7: Pooled Placebo	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	0 Participants
Part 2 Cohort 5: TAK-925 44.8 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	4 Participants
Part 2 Cohort 6: TAK-925 11.2 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	1 Participants
Part 2 Cohort 7: TAK-925 5 mg	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	0 Participants

Primary

Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)

Time frame: Baseline up to Day 7

Population: The safety analysis set was defined as all participants who received at least one dose of study drug.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1 Cohort 1-2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 1: TAK-925 7 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 2: TAK-925 14 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 1: TAK-925 28 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	1 Participants
Par 1 Cohort 2: TAK-925 56 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 1: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	1 Participants
Part 1 Cohort 2: TAK-925 134.4 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort S1-S2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort S1: TAK-925 180 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort S2: TAK-925 240 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 3: Placebo	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 3: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 1 Cohort 4: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 2 Cohort 5-7: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 2 Cohort 5: TAK-925 44.8 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 2 Cohort 6: TAK-925 11.2 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants
Part 2 Cohort 7: TAK-925 5 mg	Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)	0 Participants

Primary

Number of Participants Who Experience at Least One TEAE Related to Body Weight

Time frame: Baseline up to Day 7

Population: The safety analysis set was defined as all participants who received at least one dose of study drug.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1 Cohort 1-2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 1: TAK-925 7 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 2: TAK-925 14 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 1: TAK-925 28 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Par 1 Cohort 2: TAK-925 56 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 1: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 2: TAK-925 134.4 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort S1-S2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort S1: TAK-925 180 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort S2: TAK-925 240 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 3: Placebo	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 3: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 1 Cohort 4: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 2 Cohort 5-7: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 2 Cohort 5: TAK-925 44.8 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 2 Cohort 6: TAK-925 11.2 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants
Part 2 Cohort 7: TAK-925 5 mg	Number of Participants Who Experience at Least One TEAE Related to Body Weight	0 Participants

Primary

Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests

Time frame: Baseline up to Day 7

Population: The safety analysis set was defined as all participants who received at least one dose of study drug.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1 Cohort 1-2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	1 Participants
Part 1 Cohort 1: TAK-925 7 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort 2: TAK-925 14 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort 1: TAK-925 28 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Par 1 Cohort 2: TAK-925 56 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	1 Participants
Part 1 Cohort 1: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort 2: TAK-925 134.4 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort S1-S2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort S1: TAK-925 180 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort S2: TAK-925 240 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	1 Participants
Part 1 Cohort 3: Placebo	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort 3: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 1 Cohort 4: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 2 Cohort 5-7: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 2 Cohort 5: TAK-925 44.8 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 2 Cohort 6: TAK-925 11.2 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants
Part 2 Cohort 7: TAK-925 5 mg	Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests	0 Participants

Primary

Number of Participants Who Experience at Least One TEAE Related to Vital Signs

Time frame: Baseline up to Day 7

Population: The safety analysis set was defined as all participants who received at least one dose of study drug.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1 Cohort 1-2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort 1: TAK-925 7 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort 2: TAK-925 14 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort 1: TAK-925 28 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Par 1 Cohort 2: TAK-925 56 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort 1: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort 2: TAK-925 134.4 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	2 Participants
Part 1 Cohort S1-S2: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort S1: TAK-925 180 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	2 Participants
Part 1 Cohort S2: TAK-925 240 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	4 Participants
Part 1 Cohort 3: Placebo	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 1 Cohort 3: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	3 Participants
Part 1 Cohort 4: TAK-925 112 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 2 Cohort 5-7: Pooled Placebo	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 2 Cohort 5: TAK-925 44.8 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	1 Participants
Part 2 Cohort 6: TAK-925 11.2 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants
Part 2 Cohort 7: TAK-925 5 mg	Number of Participants Who Experience at Least One TEAE Related to Vital Signs	0 Participants

Primary

Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24

Urine assessments were done only in Part 1, as planned.

Time frame: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here overall participants analyzed are participants who were available for this outcome measure assessment at given time period.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	198.8 microgram (mcg)	Standard Deviation 49.6
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	1.892 microgram (mcg)	Standard Deviation 0.93889
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	0.000 microgram (mcg)	Standard Deviation 0
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	1.152 microgram (mcg)	Standard Deviation 1.5202
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	5.460 microgram (mcg)	Standard Deviation 3.4291
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	426.7 microgram (mcg)	Standard Deviation 101.25
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	2.438 microgram (mcg)	Standard Deviation 2.2612
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	14.10 microgram (mcg)	Standard Deviation 2.4515
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	792.8 microgram (mcg)	Standard Deviation 253.36
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	60.87 microgram (mcg)	Standard Deviation 23.008
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	8.695 microgram (mcg)	Standard Deviation 5.3533
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	1697 microgram (mcg)	Standard Deviation 495.32
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	31.25 microgram (mcg)	Standard Deviation 26.282
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	210.5 microgram (mcg)	Standard Deviation 75.775
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	1905 microgram (mcg)	Standard Deviation 1490.9
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	40.08 microgram (mcg)	Standard Deviation 28.904
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	5228 microgram (mcg)	Standard Deviation 1785.9
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	335.8 microgram (mcg)	Standard Deviation 117.81
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	578.5 microgram (mcg)	Standard Deviation 110.3
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	5815 microgram (mcg)	Standard Deviation 1095.4
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	43.12 microgram (mcg)	Standard Deviation 8.4203
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	8163 microgram (mcg)	Standard Deviation 945.57
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	79.90 microgram (mcg)	Standard Deviation 23.679
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	1223 microgram (mcg)	Standard Deviation 76.855
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	14.37 microgram (mcg)	Standard Deviation 6.0079
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	214.3 microgram (mcg)	Standard Deviation 137.61
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	2343 microgram (mcg)	Standard Deviation 635.69
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M1	3193 microgram (mcg)	Standard Deviation 677.37
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	TAK-925	184.8 microgram (mcg)	Standard Deviation 53.662
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24	Metabolite M2	21.01 microgram (mcg)	Standard Deviation 10.331

Primary

Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.900 h*ng/mL	—
Part 1 Cohort 1-2: Pooled Placebo	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	75.77 h*ng/mL	Standard Deviation 32.409
Part 1 Cohort 1-2: Pooled Placebo	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	141.8 h*ng/mL	Standard Deviation 22.744
Part 1 Cohort 1: TAK-925 7 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	173.5 h*ng/mL	Standard Deviation 53.475
Part 1 Cohort 1: TAK-925 7 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	5.302 h*ng/mL	Standard Deviation 1.6898
Part 1 Cohort 1: TAK-925 7 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	328.1 h*ng/mL	Standard Deviation 51.138
Part 1 Cohort 2: TAK-925 14 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	6.416 h*ng/mL	Standard Deviation 1.0512
Part 1 Cohort 2: TAK-925 14 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	523.5 h*ng/mL	Standard Deviation 88.288
Part 1 Cohort 2: TAK-925 14 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	296.1 h*ng/mL	Standard Deviation 122.5
Part 1 Cohort 1: TAK-925 28 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	1065 h*ng/mL	Standard Deviation 187.7
Part 1 Cohort 1: TAK-925 28 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	9.796 h*ng/mL	Standard Deviation 6.6369
Part 1 Cohort 1: TAK-925 28 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	618.9 h*ng/mL	Standard Deviation 221.98
Par 1 Cohort 2: TAK-925 56 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	2092 h*ng/mL	Standard Deviation 319.85
Par 1 Cohort 2: TAK-925 56 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1284 h*ng/mL	Standard Deviation 409.94
Par 1 Cohort 2: TAK-925 56 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	23.79 h*ng/mL	Standard Deviation 19.535
Part 1 Cohort 1: TAK-925 112 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1737 h*ng/mL	Standard Deviation 606.78
Part 1 Cohort 1: TAK-925 112 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	2682 h*ng/mL	Standard Deviation 519.45
Part 1 Cohort 1: TAK-925 112 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	32.29 h*ng/mL	Standard Deviation 25.766
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	3013 h*ng/mL	Standard Deviation 160.21
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	29.43 h*ng/mL	Standard Deviation 5.0744
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1764 h*ng/mL	Standard Deviation 202.65
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3112 h*ng/mL	Standard Deviation 745.48
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	4585 h*ng/mL	Standard Deviation 689.28
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	57.72 h*ng/mL	Standard Deviation 21.853
Part 1 Cohort S1: TAK-925 180 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1052 h*ng/mL	Standard Deviation 350.05
Part 1 Cohort S1: TAK-925 180 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	2590 h*ng/mL	Standard Deviation 283.03
Part 1 Cohort S1: TAK-925 180 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	16.88 h*ng/mL	Standard Deviation 9.9205
Part 1 Cohort S2: TAK-925 240 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	TAK-925	2028 h*ng/mL	Standard Deviation 196.21
Part 1 Cohort S2: TAK-925 240 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	17.22 h*ng/mL	Standard Deviation 8.8861
Part 1 Cohort S2: TAK-925 240 mg	Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1001 h*ng/mL	Standard Deviation 323.04

Primary

Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or cerebrospinal fluid (CSF) concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	138.0 hournanogram per milliliter (hng/mL)	Standard Deviation 22.546
Part 1 Cohort 1-2: Pooled Placebo	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.3676 hournanogram per milliliter (hng/mL)	Standard Deviation 0.89268
Part 1 Cohort 1-2: Pooled Placebo	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	74.10 hournanogram per milliliter (hng/mL)	Standard Deviation 31.837
Part 1 Cohort 1: TAK-925 7 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	170.7 hournanogram per milliliter (hng/mL)	Standard Deviation 50.607
Part 1 Cohort 1: TAK-925 7 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.940 hournanogram per milliliter (hng/mL)	Standard Deviation 2.575
Part 1 Cohort 1: TAK-925 7 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	323.1 hournanogram per milliliter (hng/mL)	Standard Deviation 45.793
Part 1 Cohort 2: TAK-925 14 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	5.893 hournanogram per milliliter (hng/mL)	Standard Deviation 2.8201
Part 1 Cohort 2: TAK-925 14 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	513.3 hournanogram per milliliter (hng/mL)	Standard Deviation 81.392
Part 1 Cohort 2: TAK-925 14 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	293.1 hournanogram per milliliter (hng/mL)	Standard Deviation 120.91
Part 1 Cohort 1: TAK-925 28 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	9.225 hournanogram per milliliter (hng/mL)	Standard Deviation 6.3231
Part 1 Cohort 1: TAK-925 28 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	1055 hournanogram per milliliter (hng/mL)	Standard Deviation 178.49
Part 1 Cohort 1: TAK-925 28 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	613.8 hournanogram per milliliter (hng/mL)	Standard Deviation 218.79
Par 1 Cohort 2: TAK-925 56 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	2069 hournanogram per milliliter (hng/mL)	Standard Deviation 298.89
Par 1 Cohort 2: TAK-925 56 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1272 hournanogram per milliliter (hng/mL)	Standard Deviation 409.93
Par 1 Cohort 2: TAK-925 56 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	22.79 hournanogram per milliliter (hng/mL)	Standard Deviation 19.464
Part 1 Cohort 1: TAK-925 112 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1724 hournanogram per milliliter (hng/mL)	Standard Deviation 596.04
Part 1 Cohort 1: TAK-925 112 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	2655 hournanogram per milliliter (hng/mL)	Standard Deviation 495.32
Part 1 Cohort 1: TAK-925 112 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	31.23 hournanogram per milliliter (hng/mL)	Standard Deviation 25.058
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	2994 hournanogram per milliliter (hng/mL)	Standard Deviation 164.73
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	28.69 hournanogram per milliliter (hng/mL)	Standard Deviation 4.946
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1762 hournanogram per milliliter (hng/mL)	Standard Deviation 204.3
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3094 hournanogram per milliliter (hng/mL)	Standard Deviation 740.81
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	4542 hournanogram per milliliter (hng/mL)	Standard Deviation 698.25
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	56.79 hournanogram per milliliter (hng/mL)	Standard Deviation 21.993
Part 1 Cohort S1: TAK-925 180 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	1037 hournanogram per milliliter (hng/mL)	Standard Deviation 343.8
Part 1 Cohort S1: TAK-925 180 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	2546 hournanogram per milliliter (hng/mL)	Standard Deviation 274.48
Part 1 Cohort S1: TAK-925 180 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	15.96 hournanogram per milliliter (hng/mL)	Standard Deviation 9.4609
Part 1 Cohort S2: TAK-925 240 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	2011 hournanogram per milliliter (hng/mL)	Standard Deviation 195
Part 1 Cohort S2: TAK-925 240 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	16.81 hournanogram per milliliter (hng/mL)	Standard Deviation 8.798
Part 1 Cohort S2: TAK-925 240 mg	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	996.3 hournanogram per milliliter (hng/mL)	Standard Deviation 321.79

Primary

Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	7.532 ng/mL	Standard Deviation 3.4019
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	13.37 ng/mL	Standard Deviation 2.0174
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.2289 ng/mL	Standard Deviation 0.12885
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.3978 ng/mL	Standard Deviation 0.23853
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	29.81 ng/mL	Standard Deviation 4.2579
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	17.79 ng/mL	Standard Deviation 4.9179
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.5928 ng/mL	Standard Deviation 0.27538
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	28.06 ng/mL	Standard Deviation 11.208
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	52.08 ng/mL	Standard Deviation 7.2344
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.9225 ng/mL	Standard Deviation 0.54081
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	114.6 ng/mL	Standard Deviation 13.303
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	58.79 ng/mL	Standard Deviation 23.607
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	213.8 ng/mL	Standard Deviation 31.714
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	121.3 ng/mL	Standard Deviation 37.632
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.217 ng/mL	Standard Deviation 1.6608
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	167.5 ng/mL	Standard Deviation 58.242
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	290.3 ng/mL	Standard Deviation 32.096
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	3.079 ng/mL	Standard Deviation 2.3329
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	324.0 ng/mL	Standard Deviation 30.182
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	174.0 ng/mL	Standard Deviation 20.376
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.850 ng/mL	Standard Deviation 0.52592
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	295.5 ng/mL	Standard Deviation 75.002
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	493.2 ng/mL	Standard Deviation 70.335
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	4.868 ng/mL	Standard Deviation 2.3897
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	98.82 ng/mL	Standard Deviation 31.862
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	272.2 ng/mL	Standard Deviation 36.985
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.528 ng/mL	Standard Deviation 0.87452
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	TAK-925	183.5 ng/mL	Standard Deviation 15.875
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.624 ng/mL	Standard Deviation 0.96722
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	105.0 ng/mL	Standard Deviation 38.567

Primary

Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2

Urine assessments were done only in Part 1, as planned.

Time frame: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.01390 L/h	Standard Deviation 0.0071503
Part 1 Cohort 1-2: Pooled Placebo	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.664 L/h	Standard Deviation 0.8393
Part 1 Cohort 1-2: Pooled Placebo	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.000 L/h	Standard Deviation 0
Part 1 Cohort 1: TAK-925 7 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.438 L/h	Standard Deviation 0.30142
Part 1 Cohort 1: TAK-925 7 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.2182 L/h	Standard Deviation 0.2595
Part 1 Cohort 1: TAK-925 7 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.01656 L/h	Standard Deviation 0.0097578
Part 1 Cohort 2: TAK-925 14 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.4630 L/h	Standard Deviation 0.31605
Part 1 Cohort 2: TAK-925 14 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.02746 L/h	Standard Deviation 0.0053337
Part 1 Cohort 2: TAK-925 14 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.614 L/h	Standard Deviation 0.545
Part 1 Cohort 1: TAK-925 28 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.7897 L/h	Standard Deviation 0.077544
Part 1 Cohort 1: TAK-925 28 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.05672 L/h	Standard Deviation 0.018842
Part 1 Cohort 1: TAK-925 28 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.653 L/h	Standard Deviation 0.24138
Par 1 Cohort 2: TAK-925 56 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.952 L/h	Standard Deviation 0.65615
Par 1 Cohort 2: TAK-925 56 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.1020 L/h	Standard Deviation 0.03735
Par 1 Cohort 2: TAK-925 56 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.014 L/h	Standard Deviation 0.23516
Part 1 Cohort 1: TAK-925 112 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.878 L/h	Standard Deviation 0.35459
Part 1 Cohort 1: TAK-925 112 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.041 L/h	Standard Deviation 0.12104
Part 1 Cohort 1: TAK-925 112 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.1275 L/h	Standard Deviation 0.046864
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.285 L/h	Standard Deviation 0.49152
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.468 L/h	Standard Deviation 0.20508
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.1928 L/h	Standard Deviation 0.035244
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.353 L/h	Standard Deviation 0.12894
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.2705 L/h	Standard Deviation 0.031501
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.643 L/h	Standard Deviation 0.37012
Part 1 Cohort S1: TAK-925 180 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.205 L/h	Standard Deviation 0.35172
Part 1 Cohort S1: TAK-925 180 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.08337 L/h	Standard Deviation 0.053779
Part 1 Cohort S1: TAK-925 180 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.7967 L/h	Standard Deviation 0.15368
Part 1 Cohort S2: TAK-925 240 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	TAK-925	0.09053 L/h	Standard Deviation 0.018093
Part 1 Cohort S2: TAK-925 240 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.132 L/h	Standard Deviation 0.24401
Part 1 Cohort S2: TAK-925 240 mg	Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.173 L/h	Standard Deviation 0.50684

Primary

Part 1, CL: Total Clearance After Intravenous Administration for TAK-925

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Arm	Measure	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	50.00 liter per hour (L/h)	Standard Deviation 9.0785
Part 1 Cohort 1: TAK-925 7 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	43.07 liter per hour (L/h)	Standard Deviation 6.4856
Part 1 Cohort 2: TAK-925 14 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	54.20 liter per hour (L/h)	Standard Deviation 9.9541
Part 1 Cohort 1: TAK-925 28 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	53.10 liter per hour (L/h)	Standard Deviation 8.2202
Par 1 Cohort 2: TAK-925 56 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	54.10 liter per hour (L/h)	Standard Deviation 9.0437
Part 1 Cohort 1: TAK-925 112 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	50.90 liter per hour (L/h)	Standard Deviation 9.8018
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	59.83 liter per hour (L/h)	Standard Deviation 3.3381
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	52.78 liter per hour (L/h)	Standard Deviation 7.4882
Part 1 Cohort S1: TAK-925 180 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	43.50 liter per hour (L/h)	Standard Deviation 4.9651
Part 1 Cohort S2: TAK-925 240 mg	Part 1, CL: Total Clearance After Intravenous Administration for TAK-925	55.40 liter per hour (L/h)	Standard Deviation 5.2211

Primary

Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	16.70 nanogram per milliliter (ng/mL)	Standard Deviation 2.8896
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.2379 nanogram per milliliter (ng/mL)	Standard Deviation 0.11806
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	8.458 nanogram per milliliter (ng/mL)	Standard Deviation 3.5972
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	19.50 nanogram per milliliter (ng/mL)	Standard Deviation 4.9426
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.4290 nanogram per milliliter (ng/mL)	Standard Deviation 0.24813
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	36.83 nanogram per milliliter (ng/mL)	Standard Deviation 4.3976
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.7051 nanogram per milliliter (ng/mL)	Standard Deviation 0.33672
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	57.56 nanogram per milliliter (ng/mL)	Standard Deviation 8.2309
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	31.82 nanogram per milliliter (ng/mL)	Standard Deviation 11.983
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.076 nanogram per milliliter (ng/mL)	Standard Deviation 0.63619
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	122.6 nanogram per milliliter (ng/mL)	Standard Deviation 13.014
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	67.69 nanogram per milliliter (ng/mL)	Standard Deviation 20.931
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	235.2 nanogram per milliliter (ng/mL)	Standard Deviation 40.712
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	134.1 nanogram per milliliter (ng/mL)	Standard Deviation 45.828
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.564 nanogram per milliliter (ng/mL)	Standard Deviation 2.037
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	189.2 nanogram per milliliter (ng/mL)	Standard Deviation 60.185
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	304.9 nanogram per milliliter (ng/mL)	Standard Deviation 50.702
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	3.422 nanogram per milliliter (ng/mL)	Standard Deviation 2.488
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	344.5 nanogram per milliliter (ng/mL)	Standard Deviation 23.549
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	3.279 nanogram per milliliter (ng/mL)	Standard Deviation 0.53902
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	197.8 nanogram per milliliter (ng/mL)	Standard Deviation 26.011
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	333.2 nanogram per milliliter (ng/mL)	Standard Deviation 70.509
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	506.3 nanogram per milliliter (ng/mL)	Standard Deviation 87.027
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	6.611 nanogram per milliliter (ng/mL)	Standard Deviation 2.235
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	106.7 nanogram per milliliter (ng/mL)	Standard Deviation 30.612
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	278.4 nanogram per milliliter (ng/mL)	Standard Deviation 33.127
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.751 nanogram per milliliter (ng/mL)	Standard Deviation 0.90125
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	TAK-925	237.8 nanogram per milliliter (ng/mL)	Standard Deviation 25.695
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.022 nanogram per milliliter (ng/mL)	Standard Deviation 0.99882
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	114.4 nanogram per milliliter (ng/mL)	Standard Deviation 38.575

Primary

Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2

Urine assessments were done only in Part 1, as planned.

Time frame: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.028 percentage of dose	Standard Deviation 0.0148
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.000 percentage of dose	Standard Deviation 0
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.736 percentage of dose	Standard Deviation 0.6841
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.938 percentage of dose	Standard Deviation 0.695
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.008 percentage of dose	Standard Deviation 0.0117
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.038 percentage of dose	Standard Deviation 0.0232
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.008 percentage of dose	Standard Deviation 0.0084
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.050 percentage of dose	Standard Deviation 0.0071
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.726 percentage of dose	Standard Deviation 0.8677
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.017 percentage of dose	Standard Deviation 0.0103
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.110 percentage of dose	Standard Deviation 0.0424
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.920 percentage of dose	Standard Deviation 0.8519
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.190 percentage of dose	Standard Deviation 0.0657
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.358 percentage of dose	Standard Deviation 1.2922
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.025 percentage of dose	Standard Deviation 0.0243
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.748 percentage of dose	Standard Deviation 1.2809
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.250 percentage of dose	Standard Deviation 0.0883
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.028 percentage of dose	Standard Deviation 0.0214
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.322 percentage of dose	Standard Deviation 0.0624
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.023 percentage of dose	Standard Deviation 0.0052
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.112 percentage of dose	Standard Deviation 0.5872
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.280 percentage of dose	Standard Deviation 0.3788
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.508 percentage of dose	Standard Deviation 0.0319
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.032 percentage of dose	Standard Deviation 0.0117
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.015 percentage of dose	Standard Deviation 0.5452
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.192 percentage of dose	Standard Deviation 0.1237
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.013 percentage of dose	Standard Deviation 0.0082
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	TAK-925	0.165 percentage of dose	Standard Deviation 0.048
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	0.018 percentage of dose	Standard Deviation 0.0096
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.748 percentage of dose	Standard Deviation 0.5871

Primary

Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4

Time frame: Day 1 at 6 hours after start of infusion

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4	TAK-925	0.02848 Ratio	Standard Deviation 0.0056258
Part 1 Cohort 1-2: Pooled Placebo	Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4	Metabolite M1	0.06190 Ratio	Standard Deviation 0.010358
Part 1 Cohort 1-2: Pooled Placebo	Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4	Metabolite M2	0.02818 Ratio	Standard Deviation 0.032718

Primary

Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	4.120 hours	Standard Deviation 1.919
Part 1 Cohort 1-2: Pooled Placebo	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.670 hours	—
Part 1 Cohort 1-2: Pooled Placebo	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.598 hours	Standard Deviation 1.3239
Part 1 Cohort 1: TAK-925 7 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.443 hours	Standard Deviation 0.9386
Part 1 Cohort 1: TAK-925 7 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.8975 hours	Standard Deviation 0.2583
Part 1 Cohort 1: TAK-925 7 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	4.498 hours	Standard Deviation 1.7725
Part 1 Cohort 2: TAK-925 14 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.545 hours	Standard Deviation 0.1237
Part 1 Cohort 2: TAK-925 14 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	5.142 hours	Standard Deviation 1.806
Part 1 Cohort 2: TAK-925 14 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.122 hours	Standard Deviation 0.4673
Part 1 Cohort 1: TAK-925 28 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.692 hours	Standard Deviation 0.7082
Part 1 Cohort 1: TAK-925 28 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	3.860 hours	Standard Deviation 0.6478
Part 1 Cohort 1: TAK-925 28 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.760 hours	Standard Deviation 0.895
Par 1 Cohort 2: TAK-925 56 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	3.788 hours	Standard Deviation 1.0424
Par 1 Cohort 2: TAK-925 56 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.075 hours	Standard Deviation 0.5984
Par 1 Cohort 2: TAK-925 56 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.158 hours	Standard Deviation 0.7646
Part 1 Cohort 1: TAK-925 112 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.825 hours	Standard Deviation 0.5203
Part 1 Cohort 1: TAK-925 112 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	3.943 hours	Standard Deviation 0.9492
Part 1 Cohort 1: TAK-925 112 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.847 hours	Standard Deviation 1.5995
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	3.363 hours	Standard Deviation 0.8523
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.702 hours	Standard Deviation 0.4891
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.205 hours	Standard Deviation 0.2616
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.637 hours	Standard Deviation 0.5575
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	4.033 hours	Standard Deviation 1.2843
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.818 hours	Standard Deviation 1.0856
Part 1 Cohort S1: TAK-925 180 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	3.763 hours	Standard Deviation 0.7675
Part 1 Cohort S1: TAK-925 180 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	4.345 hours	Standard Deviation 0.5901
Part 1 Cohort S1: TAK-925 180 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	2.727 hours	Standard Deviation 1.3977
Part 1 Cohort S2: TAK-925 240 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	TAK-925	4.490 hours	Standard Deviation 1.5939
Part 1 Cohort S2: TAK-925 240 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M2	1.205 hours	Standard Deviation 0.2873
Part 1 Cohort S2: TAK-925 240 mg	Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2	Metabolite M1	2.400 hours	Standard Deviation 0.6307

Primary

Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Population: The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here number analyzed were participants who were evaluable for the outcome measure at given time points.

Arm	Measure	Group	Value (MEDIAN)
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	3.000 hours
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	7.500 hours
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	8.000 hours
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	4.000 hours
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	4.000 hours
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	3.000 hours
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	6.000 hours
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	4.000 hours
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	4.000 hours
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	4.000 hours
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	6.500 hours
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	4.000 hours
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	6.500 hours
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	5.000 hours
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	4.000 hours
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	3.500 hours
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	6.000 hours
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	6.500 hours
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	3.000 hours
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	TAK-925	5.000 hours
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M2	3.500 hours
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2	Metabolite M1	8.000 hours

Primary

Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Arm	Measure	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	82.88 liter	Standard Deviation 29.543
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	77.07 liter	Standard Deviation 22.804
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	116.1 liter	Standard Deviation 35.215
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	91.40 liter	Standard Deviation 14.122
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	97.83 liter	Standard Deviation 22.194
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	88.47 liter	Standard Deviation 12.476
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	90.75 liter	Standard Deviation 24.14
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	97.48 liter	Standard Deviation 28.378
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	99.48 liter	Standard Deviation 15.472
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925	77.98 liter	Standard Deviation 28.931

Primary

Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925

Time frame: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion

Arm	Measure	Value (MEAN)	Dispersion
Part 1 Cohort 1-2: Pooled Placebo	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	292.2 liter	Standard Deviation 124.03
Part 1 Cohort 1: TAK-925 7 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	271.7 liter	Standard Deviation 79.238
Part 1 Cohort 2: TAK-925 14 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	391.8 liter	Standard Deviation 117.09
Part 1 Cohort 1: TAK-925 28 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	290.7 liter	Standard Deviation 31.156
Par 1 Cohort 2: TAK-925 56 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	288.8 liter	Standard Deviation 55.185
Part 1 Cohort 1: TAK-925 112 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	284.7 liter	Standard Deviation 65.265
Part 1 Cohort 2: TAK-925 134.4 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	290.8 liter	Standard Deviation 77.783
Part 1 Cohort S1-S2: Pooled Placebo	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	313.0 liter	Standard Deviation 128.81
Part 1 Cohort S1: TAK-925 180 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	271.5 liter	Standard Deviation 39.145
Part 1 Cohort S2: TAK-925 240 mg	Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925	357.3 liter	Standard Deviation 121.15

Primary