A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-925 in Healthy Volunteers and Participants With Narcolepsy

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03748979
• Collaborator: (none)
• Enrollment: 57
• Locations: 3
• Arms: 17
• Actual Duration (Months): 11.1
• Patients Per Site: 19
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925 when administered to healthy participants and narcolepsy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants; Narcolepsy	Drug: TAK-925; Drug: Placebo	Phase 1

Detailed Description

The drug being tested in this study is called TAK-925. TAK-925 is being tested in healthy participants and participants with narcolepsy. This study will look at the safety, tolerability, pharmacokinetics, and efficacy of TAK-925.

This study will consist of three parts. Part A will be a randomized, double-blind, placebo-controlled, multiple rising dose (MRD) study in healthy participants. Part B is a randomized, double-blind, placebo-controlled MRD study in participants with narcolepsy. Part C is a randomized, double-blind, placebo-controlled, parallel group, multiple repeat dose study in participants with narcolepsy. Part A' is a single dose study in healthy participants.

The study will enroll approximately 96 participants planned as total. All participants except Part A' will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need):

Part A:

• TAK-925 (Dose Levels A1-A6)

• Placebo

Part B:

• TAK-925 (Dose Levels B1-B4)

• Placebo

Part C:

• TAK-925 (Dose Levels C1-C2)

• Placebo

Part A':

• TAK-925 (Dose Levels A'1-A'2)

All participants will be asked to take TAK-925 or Placebo at the same time each day from Day 1 to Day 7 in Parts A, B and C, and take TAK-925 on Day 1 in Part A'.

This multi-center trial will be conducted in Japan. The overall study period is approximately 15 days in Parts A, B and C, and approximately 7 days for Part A'. Participants will be partly admitted to a hospital during the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 3-Part, Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-925 in Healthy Volunteers and Patients With Narcolepsy
• Actual Study Start Date: Nov 21, 2018
• Actual Primary Completion Date: Oct 24, 2019
• Actual Study Completion Date: Oct 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A1; TAK-925 (Dose Level A1) TAK-925, Dose Level A, once daily for up to 7 days in healthy participants.	Drug: TAK-925; TAK-925
Experimental: Cohort A2; TAK-925 (Dose Level A2) TAK-925, Dose Level A2, once daily for up to 7 days in healthy participants. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A3; TAK-925 (Dose Level A3) TAK-925, Dose Level A3, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A4; TAK-925 (Dose Level A4) TAK-925, Dose Level A4, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A5; TAK-925 (Dose Level A5) TAK-925, Dose Level A5, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort A6; TAK-925 (Dose Level A6) TAK-925, Dose Level A6, once daily for up to 7 days in healthy elderly participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Placebo Comparator: Part A (Cohorts A1-A6); TAK-925 Placebo TAK-925 Placebo, once daily for up to 7 days in healthy participants.	Drug: Placebo; TAK-925 Placebo
Experimental: Cohort B1; TAK-925 (Dose Level B1) TAK-925, Dose Level B1, once daily for up to 7 days in participants with narcolepsy.	Drug: TAK-925; TAK-925
Experimental: Cohort B2; TAK-925 (Dose Level B2) TAK-925, Dose Level B2, once daily for up to 7 days in participants with narcolepsy. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort B3; TAK-925 (Dose Level B3) TAK-925, Dose Level B3, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort B4; TAK-925 (Dose Level B4) TAK-925, Dose Level B4, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Placebo Comparator: Part B (Cohorts B1-B4); TAK-925 Placebo TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.	Drug: Placebo; TAK-925 Placebo
Experimental: Cohort C1; TAK-925 (Dose Level C1) TAK-925, Dose Level C1, once daily for up to 7 days in participants with narcolepsy. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Experimental: Cohort C2; TAK-925 (Dose Level C2) TAK-925, Dose Level C2, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925
Placebo Comparator: Part C (Cohorts C1-C2); TAK-925 Placebo TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.	Drug: Placebo; TAK-925 Placebo
Experimental: Cohort A'1; TAK-925 (Dose Level A'1) TAK-925, Dose Level A'1, single dose in healthy participants.	Drug: TAK-925; TAK-925
Experimental: Cohort A'2; TAK-925 (Dose Level A'2) TAK-925, Dose Level A'2, single dose in healthy participants. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.	Drug: TAK-925; TAK-925

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)]

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

Secondary Outcome Measures

1. Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 [Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf]

   This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

2. Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 [Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf]

   This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

3. Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 [Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf]

   Accumulation Ratio of AUC was calculated as AUCtau on Day 7 divided by AUCtau on Day 1. This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.

4. Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 [Baseline, Day 1 and Day 7]

   The MWT is a validated objective measure that is used to measure excessive daytime sleepiness in clinical studies. It has been used as a secondary outcome measure for excessive daytime sleepiness. The MWT evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Wakefulness in this study was measured indirectly by time to fall asleep using MWT. In this study, four 40-minute (1 session) MWT assessments per day was administered on Baseline, Day 1 and Day 7. MWT sleep latency ranges from 0 to 40 minutes, with longer sleep latency indicating greater ability to stay awake.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Healthy adult participants and Healthy elderly participants:

• Participant weighs at least 50 kg (Healthy adults participants) / 40 kilogram (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 participants:

• Participants weighs at least 40 kg inclusive at Screening (>=50 kg is required for Cohort B4).

• A diagnosis of narcolepsy, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3).

• At Day -1, Epworth sleepiness scale (ESS) score >=10

Exclusion Criteria:

All Participants:

• Participants consume excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.

• Participants have a moderate to severe substance use disorder.

• Participants have a risk of suicide according to endorsement of item 4 or 5 with Screening/Baseline visit C-SSRS (Columbia Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.

• Participants have a lifetime history of major psychiatric disorder, such as bipolar disorder or schizophrenia.

• Participants experienced sleep wake cycle disturbance with external factors such as irregular work hours.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sumida Hospital	Sumida-ku	Tokyo	Japan
2	Hakata Clinic	Fukuoka		Japan
3	PS Clinic	Fukuoka		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Statistical Analysis Plan - Oct 28, 2019
• Study Protocol - Jun 12, 2019

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03748979
• Other Study ID Numbers: TAK-925-1003; U1111-1221-3144; JapicCTI-184207
• First Posted: Nov 21, 2018
• Last Update Posted: Dec 8, 2020
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Narcolepsy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 3 investigative sites in Japan from 21 November 2018 to 24 October 2019.
Pre-assignment Detail	Healthy participants were enrolled in Part A and A' (exploratory), NT1 in Part B and NT2 in Part C, to receive TAK-925 multiple rising dose of 44 mg (milligram), 112 mg,180 mg or placebo in Part A, 11 mg, 44 mg or placebo in Part B, multiple dose of TAK-925 44 mg, 112 mg or placebo in Part C.

Arm/Group Title	Part A, Cohorts A1-A3: Pooled Placebo	Part A, Cohort A1: TAK-925 44 mg	Part A, Cohort A2: TAK-925 112 mg	Part A, Cohort A3: TAK-925 180 mg	Part B, Cohorts B1-B2: Pooled Placebo	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohorts C1-C2: Pooled Placebo	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg	Part A', Cohort A'1: TAK-925 112 mg
Arm/Group Description	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in narcolepsy type 1 (NT1) participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in narcolepsy type 2 (NT2) participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, solution, orally, once on Day 1 in healthy participants.
Period Title: Overall Study
STARTED	6	6	6	6	4	4	5	5	4	5	6
COMPLETED	6	6	6	6	4	4	5	5	4	5	6
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A, Cohorts A1-A3: Pooled Placebo	Part A, Cohort A1: TAK-925 44 mg	Part A, Cohort A2: TAK-925 112 mg	Part A, Cohort A3: TAK-925 180 mg	Part B, Cohorts B1-B2: Pooled Placebo	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohorts C1-C2: Pooled Placebo	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg	Part A', Cohort A'1: TAK-925 112 mg	Total
Arm/Group Description	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, solution, orally, once on Day 1 in healthy participants.	Total of all reporting groups
Overall Participants	6	6	6	6	4	4	5	5	4	5	6	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.8 (4.71)	24.7 (3.88)	23.8 (3.54)	22.3 (0.52)	28.3 (9.18)	38.0 (3.92)	27.6 (8.20)	31.8 (11.14)	31.3 (7.50)	25.0 (5.87)	21.7 (2.88)	26.6 (7.04)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	1 25%	2 50%	2 40%	3 60%	3 75%	2 40%	0 0%	13 22.8%
Male	6 100%	6 100%	6 100%	6 100%	3 75%	2 50%	3 60%	2 40%	1 25%	3 60%	6 100%	44 77.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Japan	6 100%	6 100%	6 100%	6 100%	4 100%	4 100%	5 100%	5 100%	4 100%	5 100%	6 100%	57 100%
Body Mass Index (BMI) (kilogram per square meter (kg/m˄2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m˄2)]	22.42 (0.968)	21.12 (1.030)	22.37 (1.960)	21.87 (2.360)	24.83 (2.378)	27.33 (4.955)	24.68 (4.791)	20.88 (3.565)	22.83 (4.213)	22.18 (3.489)	21.05 (1.174)	22.66 (3.210)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	170.2 (4.71)	173.3 (4.84)	168.8 (5.85)	170.8 (4.71)	169.8 (7.80)	165.3 (8.18)	166.8 (7.56)	162.2 (5.02)	158.0 (5.60)	164.6 (5.46)	170.7 (3.44)	167.8 (6.63)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	64.58 (5.486)	62.75 (3.250)	63.72 (7.392)	63.60 (7.987)	72.90 (13.071)	75.20 (18.150)	70.32 (15.554)	56.20 (11.689)	57.73 (13.072)	61.68 (10.055)	60.60 (4.549)	64.14 (10.706)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Description	An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug.
Time Frame	From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A, Cohorts A1-A3: Pooled Placebo	Part A, Cohort A1: TAK-925 44 mg	Part A, Cohort A2: TAK-925 112 mg	Part A, Cohort A3: TAK-925 180 mg	Part B, Cohorts B1-B2: Pooled Placebo	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohorts C1-C2: Pooled Placebo	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg	Part A', Cohort A'1: TAK-925 112 mg
Arm/Group Description	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, solution, orally, once on Day 1 in healthy participants.
Measure Participants	6	6	6	6	4	4	5	5	4	5	6
Count of Participants [Participants]	1 16.7%	0 0%	2 33.3%	4 66.7%	1 25%	1 25%	5 100%	0 0%	1 25%	3 60%	0 0%

2. Secondary Outcome

Title	Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925
Description	This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.
Time Frame	Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set was defined as all participants who received at least one dose of study drug and provided sufficient PK measurements available to estimate PK parameters, at least 1 estimable PK parameter.

Arm/Group Title	Part A, Cohort A1: TAK-925 44 mg	Part A, Cohort A2: TAK-925 112 mg	Part A, Cohort A3: TAK-925 180 mg	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg
Arm/Group Description	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.
Measure Participants	6	6	6	4	5	4	5
Day 1	74.49 (4.3433)	166.9 (20.995)	300.2 (50.532)	17.39 (1.2842)	70.20 (18.798)	68.74 (7.3623)	156.1 (29.210)
Day 7	70.31 (8.4434)	159.2 (23.560)	295.5 (46.173)	17.68 (1.7176)	73.20 (14.980)	70.87 (7.4375)	153.9 (24.876)

3. Secondary Outcome

Title	Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925
Description	This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.
Time Frame	Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf

Outcome Measure Data

Analysis Population Description

The PK set was defined as all participants who received at least one dose of study drug and provided sufficient PK measurements available to estimate PK parameters, at least 1 estimable PK parameter.

Arm/Group Title	Part A, Cohort A1: TAK-925 44 mg	Part A, Cohort A2: TAK-925 112 mg	Part A, Cohort A3: TAK-925 180 mg	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg
Arm/Group Description	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.
Measure Participants	6	6	6	4	5	4	5
Day 1	662.4 (70.718)	1516 (151.45)	2615 (392.89)	164.2 (18.257)	682.3 (126.81)	648.3 (80.748)	1496 (279.16)
Day 7	650.7 (78.156)	1523 (174.40)	2747 (372.96)	182.7 (22.603)	722.7 (102.28)	657.1 (72.833)	1519 (248.46)

4. Secondary Outcome

Title	Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925
Description	Accumulation Ratio of AUC was calculated as AUCtau on Day 7 divided by AUCtau on Day 1. This assessment was pre-specified to be conducted for participants in "Part A', Cohort A'1: TAK-925 112 mg" as exploratory measures.
Time Frame	Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf

Outcome Measure Data

Analysis Population Description

The PK set was defined as all participants who received at least one dose of study drug and provided sufficient PK measurements available to estimate PK parameters, at least 1 estimable PK parameter.

Arm/Group Title	Part A, Cohort A1: TAK-925 44 mg	Part A, Cohort A2: TAK-925 112 mg	Part A, Cohort A3: TAK-925 180 mg	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg
Arm/Group Description	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.
Measure Participants	6	6	6	4	5	4	5
Mean (Standard Deviation) [ratio]	0.9832 (0.041034)	1.009 (0.080171)	1.050 (0.020000)	1.118 (0.14637)	1.062 (0.066062)	1.017 (0.098127)	1.018 (0.030760)

5. Secondary Outcome

Title	Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7
Description	The MWT is a validated objective measure that is used to measure excessive daytime sleepiness in clinical studies. It has been used as a secondary outcome measure for excessive daytime sleepiness. The MWT evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Wakefulness in this study was measured indirectly by time to fall asleep using MWT. In this study, four 40-minute (1 session) MWT assessments per day was administered on Baseline, Day 1 and Day 7. MWT sleep latency ranges from 0 to 40 minutes, with longer sleep latency indicating greater ability to stay awake.
Time Frame	Baseline, Day 1 and Day 7

Outcome Measure Data

Analysis Population Description

The pharmacodynamic (PD) set was defined as all participants who received at least one dose of study drug. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.

Arm/Group Title	Part B, Cohorts B1-B2: Pooled Placebo	Part B, Cohort B1: TAK-925 11 mg	Part B, Cohort B2: TAK-925 44 mg	Part C, Cohorts C1-C2: Pooled Placebo	Part C, Cohort C1: TAK-925 44 mg	Part C, Cohort C2: TAK-925 112 mg
Arm/Group Description	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.	TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.
Measure Participants	4	4	5	5	4	5
Baseline	1.97 (0.850)	2.03 (0.717)	5.23 (4.029)	4.13 (3.280)	6.83 (3.924)	7.33 (5.932)
Change at Day 1	-0.66 (0.892)	35.13 (4.268)	34.19 (4.398)	2.58 (3.751)	23.88 (2.955)	31.15 (5.507)
Change at Day 7	-0.38 (0.621)	21.00 (12.141)	34.78 (4.029)	2.35 (3.369)	25.79 (7.544)	28.28 (4.886)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohorts A1-A3: Pooled Placebo, Part A, Cohort A1: TAK-925 44 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 1.
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohorts A1-A3: Pooled Placebo, Part A, Cohort A2: TAK-925 112 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 1.
	Method	MMRM
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohorts A1-A3: Pooled Placebo, Part A, Cohort A1: TAK-925 44 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 7.
	Method	MMRM
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohorts A1-A3: Pooled Placebo, Part A, Cohort A2: TAK-925 112 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 7.
	Method	MMRM
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort A3: TAK-925 180 mg, Part B, Cohorts B1-B2: Pooled Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 1.
	Method	MMRM
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort A3: TAK-925 180 mg, Part B, Cohort B1: TAK-925 11 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 1.
	Method	MMRM
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort A3: TAK-925 180 mg, Part B, Cohorts B1-B2: Pooled Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 7.
	Method	MMRM
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort A3: TAK-925 180 mg, Part B, Cohort B1: TAK-925 11 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was obtained using MMRM analysis. The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group on Day 7.
	Method	MMRM
	Comments

Adverse Events

Time Frame	TEAEs are adverse events (AEs) that started after the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Part A, Cohorts A1-A3: Pooled Placebo		Part A, Cohort A1: TAK-925 44 mg		Part A, Cohort A2: TAK-925 112 mg		Part A, Cohort A3: TAK-925 180 mg		Part B, Cohorts B1-B2: Pooled Placebo		Part B, Cohort B1: TAK-925 11 mg		Part B, Cohort B2: TAK-925 44 mg		Part C, Cohorts C1-C2: Pooled Placebo		Part C, Cohort C1: TAK-925 44 mg		Part C, Cohort C2: TAK-925 112 mg		Part A', Cohort A'1: TAK-925 112 mg
Arm/Group Description	TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.		TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.		TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.		TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants.		TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.		TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.		TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants.		TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.		TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.		TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants.		TAK-925 112 mg, solution, orally, once on Day 1 in healthy participants.
All Cause Mortality
	Part A, Cohorts A1-A3: Pooled Placebo		Part A, Cohort A1: TAK-925 44 mg		Part A, Cohort A2: TAK-925 112 mg		Part A, Cohort A3: TAK-925 180 mg		Part B, Cohorts B1-B2: Pooled Placebo		Part B, Cohort B1: TAK-925 11 mg		Part B, Cohort B2: TAK-925 44 mg		Part C, Cohorts C1-C2: Pooled Placebo		Part C, Cohort C1: TAK-925 44 mg		Part C, Cohort C2: TAK-925 112 mg		Part A', Cohort A'1: TAK-925 112 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Serious Adverse Events
	Part A, Cohorts A1-A3: Pooled Placebo		Part A, Cohort A1: TAK-925 44 mg		Part A, Cohort A2: TAK-925 112 mg		Part A, Cohort A3: TAK-925 180 mg		Part B, Cohorts B1-B2: Pooled Placebo		Part B, Cohort B1: TAK-925 11 mg		Part B, Cohort B2: TAK-925 44 mg		Part C, Cohorts C1-C2: Pooled Placebo		Part C, Cohort C1: TAK-925 44 mg		Part C, Cohort C2: TAK-925 112 mg		Part A', Cohort A'1: TAK-925 112 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Part A, Cohorts A1-A3: Pooled Placebo		Part A, Cohort A1: TAK-925 44 mg		Part A, Cohort A2: TAK-925 112 mg		Part A, Cohort A3: TAK-925 180 mg		Part B, Cohorts B1-B2: Pooled Placebo		Part B, Cohort B1: TAK-925 11 mg		Part B, Cohort B2: TAK-925 44 mg		Part C, Cohorts C1-C2: Pooled Placebo		Part C, Cohort C1: TAK-925 44 mg		Part C, Cohort C2: TAK-925 112 mg		Part A', Cohort A'1: TAK-925 112 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		4/6 (66.7%)		1/4 (25%)		1/4 (25%)		5/5 (100%)		0/5 (0%)		1/4 (25%)		3/5 (60%)		0/6 (0%)
Gastrointestinal disorders
Salivary hypersecretion	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		0/6 (0%)
Nausea	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/5 (0%)		1/4 (25%)		0/5 (0%)		0/6 (0%)
Diarrhoea	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		1/4 (25%)		0/5 (0%)		0/6 (0%)
General disorders
Feeling abnormal	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Asthenia	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Infections and infestations
Nasopharyngitis	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Gastroenteritis	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		0/6 (0%)
Investigations
Blood pressure increased	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		1/5 (20%)		0/6 (0%)
Nervous system disorders
Headache	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Renal and urinary disorders
Pollakiuria	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		4/5 (80%)		0/5 (0%)		0/4 (0%)		2/5 (40%)		0/6 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Hyperhidrosis	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)
Vascular disorders
Hot flush	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/5 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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