Healthy Participants and Patients With NarcolepsyPhase 1NCT03332784

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

A Phase 1 study testing TAK-925 in people with Healthy Participants and Patients With Narcolepsy, run by Takeda at 3 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Participants and Patients With Narcolepsy
What is being tested?: TAK-925
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 58 participants
Where: 3 sitesJapan
Study dates: 4 Nov 2017to 4 Sep 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

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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.

Trial locations and contacts

3 sites in 1 country.

Japan3 sites

Hakata Clinic
Fukuoka
PS Clinic
Fukuoka
Sumida Hospital
Sumida-ku, Tokyo

Other trials in Japan

About this study

Official title: 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

Read the 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.

Conditions: Healthy Participants and Patients With Narcolepsy
Being tested: TAK-925, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TAK-925Drug
TAK-925 Intravenous Infusion
PlaceboDrug
TAK-925 Placebo Intravenous Infusion

Study groups in NCT03332784
Study group	Role	What they receive
Part 1: TAK-925 (Cohort 1; Dose Level 1)	Experimental	TAK-925, Intravenous single administration. Healthy adults will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: TAK-925 (Cohort 2; Dose Level 2)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 2). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: TAK-925 (Cohort 1; Dose Level 3)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 3). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: TAK-925 (Cohort 2; Dose Level 4)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 4). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: TAK-925 (Cohort 1; Dose Level 5)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: TAK-925 (Cohort 2; Dose Level 6)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 6). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: Placebo (Cohort 1-2)	Placebo comparator	TAK-925 Placebo, Intravenous single administration. Healthy adults will be enrolled in double blind manner. Receives: Drug: Placebo
Part 1: TAK-925 (Cohort 3; Dose Level 5)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy elderly participants will be enrolled in double blind manner. Receives: Drug: TAK-925
Part 1: Placebo (Cohort 3)	Placebo comparator	TAK-925 Placebo, Intravenous single administration. Healthy elderly participants will be enrolled in double blind manner. Receives: Drug: Placebo
Part 1: TAK-925 (Cohort 4; Dose Level 5)	Experimental	TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy adults will be enrolled in non-blinded manner. Receives: Drug: TAK-925
Part 2: TAK-925 TBD (Cohort 5)	Experimental	TAK-925, Intravenous single administration. Dose in Cohort 5 will be based on safety and tolerability in the Part 1. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). Receives: Drug: TAK-925
Part 2: TAK-925 TBD (Cohort 6)	Experimental	TAK-925, Intravenous single administration. Dose in Cohort 6 TBD based on safety, tolerability, PK data, and results of the Maintenance Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). Receives: Drug: TAK-925
Part 2: TAK-925 TBD (Cohort 7)	Experimental	TAK-925, Intravenous single administration. Dose in Cohort 7 TBD based on safety, tolerability, PK data, and results of the Maintenance of Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). Receives: Drug: TAK-925
Part 2: Placebo (Cohort 5-7)	Placebo comparator	TAK-925 Placebo, Intravenous single administration. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Measured: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Vital Signs
Measured: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Body Weight
Measured: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)
Measured: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests
Measured: Baseline up to Day 7
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Urine assessments were done only in Part 1, as planned.
Measured: 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
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.
Measured: 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
Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2
Urine assessments were done only in Part 1, as planned.
Measured: 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
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
Measured: Day 1 at 6 hours after start of infusion

Secondary outcomes (1)

Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT)
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.
Measured: Days 1 and 3 up to 8 hours following the start of infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Nov 20174 Sep 2018

First posted6 Nov 2017
Study start4 Nov 2017
Primary completion4 Sep 2018
Study completion4 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy Participants and Patients With NarcolepsyStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03332784
Sponsor's protocol ID: TAK-925-1001
Other IDs: U1111-1201-6634, JapicCTI-173756
Status last verified: Mar 2021
First submitted: 2 Nov 2017
Last updated: 30 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03332784
Acronym / sponsor ID: TAK-925-1001
Conditions: Healthy Participants and Patients With Narcolepsy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 4 Nov 2017 (actual)
Primary completion: 4 Sep 2018 (actual)
Study completion: 4 Sep 2018 (actual)
First posted: 6 Nov 2017 (actual)
Results: Posted 18 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

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)

Part 2, Cohort 5-7

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 14

Arm	Type	Receives
Part 1: TAK-925 (Cohort 1; Dose Level 1)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Healthy adults will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 2; Dose Level 2)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 2). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 1; Dose Level 3)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 3). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 2; Dose Level 4)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 4). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 1; Dose Level 5)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 2; Dose Level 6)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 6). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Part 1: Placebo (Cohort 1-2)	Placebo comparator	Drug: PlaceboTAK-925 Placebo, Intravenous single administration. Healthy adults will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 3; Dose Level 5)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy elderly participants will be enrolled in double blind manner.
Part 1: Placebo (Cohort 3)	Placebo comparator	Drug: PlaceboTAK-925 Placebo, Intravenous single administration. Healthy elderly participants will be enrolled in double blind manner.
Part 1: TAK-925 (Cohort 4; Dose Level 5)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy adults will be enrolled in non-blinded manner.
Part 2: TAK-925 TBD (Cohort 5)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose in Cohort 5 will be based on safety and tolerability in the Part 1. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Part 2: TAK-925 TBD (Cohort 6)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose in Cohort 6 TBD based on safety, tolerability, PK data, and results of the Maintenance Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Part 2: TAK-925 TBD (Cohort 7)	Experimental	Drug: TAK-925TAK-925, Intravenous single administration. Dose in Cohort 7 TBD based on safety, tolerability, PK data, and results of the Maintenance of Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Part 2: Placebo (Cohort 5-7)	Placebo comparator	Drug: PlaceboTAK-925 Placebo, Intravenous single administration. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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.
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

Key exclusion criteria (9 listed)

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.
Participant has had CSF collection performed within 14 days prior to check-in (Day -1).
Narcolepsy patients

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TAK-925TAK-925 Intravenous Infusion	Drug	Part 1: TAK-925 (Cohort 1; Dose Level 1), Part 1: TAK-925 (Cohort 1; Dose Level 3), Part 1: TAK-925 (Cohort 1; Dose Level 5), Part 1: TAK-925 (Cohort 2; Dose Level 2), Part 1: TAK-925 (Cohort 2; Dose Level 4), Part 1: TAK-925 (Cohort 2; Dose Level 6), Part 1: TAK-925 (Cohort 3; Dose Level 5), Part 1: TAK-925 (Cohort 4; Dose Level 5), Part 2: TAK-925 TBD (Cohort 5), Part 2: TAK-925 TBD (Cohort 6), Part 2: TAK-925 TBD (Cohort 7)
PlaceboTAK-925 Placebo Intravenous Infusion	Drug	Part 1: Placebo (Cohort 1-2), Part 1: Placebo (Cohort 3), Part 2: Placebo (Cohort 5-7)

Primary outcome

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Vital Signs
Time frame: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Body Weight
Time frame: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)
Time frame: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests
Time frame: Baseline up to Day 7
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
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
Time frame: 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
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
Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2
Time frame: 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
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
Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2
Time frame: 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
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
Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2
Time frame: 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
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
Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2
Time frame: 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
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
Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2
Time frame: 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
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
Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
Time frame: 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
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
Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925
Time frame: 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
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
Part 2, CL: Total Clearance After Intravenous Administration for TAK-925
Time frame: 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
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
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
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
Urine assessments were done only in Part 1, as planned.
Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2
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
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
Time frame: Day 1 at 6 hours after start of infusion

1 secondary outcome

Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT)
Time frame: Days 1 and 3 up to 8 hours following the start of infusion

Results and safety

Results posted to the registry on 18 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + TAK-925 112 mg	2	2
Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + Placebo	2	1
Part 1 Cohort 1: TAK-925 7 mg + Placebo + TAK-925 112 mg	2	2
Part 1 Cohort 1: Placebo + TAK-925 28 mg + TAK-925 112 mg	2	2
Part 1 Cohort 2:TAK-925 14 mg +TAK-925 56 mg +TAK-925 134.4 mg	2	2
Part 1 Cohort 2: TAK-925 14 mg + TAK-925 56 mg + Placebo	2	2
Part 1 Cohort 2: TAK-925 14 mg + Placebo + TAK-925 134.4 mg	2	2
Part 1 Cohort 2: Placebo + TAK-925 56 mg + TAK-925 134.4 mg	2	2
Part 1 Cohort S1-S2: Pooled Placebo	4	4
Part 1 Cohort S1: TAK-925 180 mg	6	6
Part 1 Cohort S2: TAK-925 240 mg	6	6
Part 1 Cohort 3: Placebo	2	2
Part 1 Cohort 3: TAK-925 112 mg	6	6
Part 1 Cohort 4: TAK-925 112 mg	4	4
Part 2 Cohort 5: TAK-925 44.8 mg + Placebo	2	1
Part 2 Cohort 5: Placebo + TAK-925 44.8 mg	2	2
Part 2 Cohort 6: TAK-925 11.2 mg + Placebo	2	2
Part 2 Cohort 6: Placebo + TAK-925 11.2 mg	2	2
Part 2 Cohort 7: TAK-925 5 mg + Placebo	3	3
Part 2 Cohort 7: Placebo + TAK-925 5 mg	3	3

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

Time frame: Baseline up to Day 7. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1-2: Pooled Placebo n = 11	Part 1 Cohort 1: TAK-925 7 mg n = 6	Part 1 Cohort 2: TAK-925 14 mg n = 6	Part 1 Cohort 1: TAK-925 28 mg n = 5	Par 1 Cohort 2: TAK-925 56 mg n = 6	Part 1 Cohort 1: TAK-925 112 mg n = 6	Part 1 Cohort 2: TAK-925 134.4 mg n = 6	Part 1 Cohort S1-S2: Pooled Placebo n = 4	Part 1 Cohort S1: TAK-925 180 mg n = 6	Part 1 Cohort S2: TAK-925 240 mg n = 6	Part 1 Cohort 3: Placebo n = 2	Part 1 Cohort 3: TAK-925 112 mg n = 6	Part 1 Cohort 4: TAK-925 112 mg n = 4	Part 2 Cohort 5-7: Pooled Placebo n = 13	Part 2 Cohort 5: TAK-925 44.8 mg n = 4	Part 2 Cohort 6: TAK-925 11.2 mg n = 4	Part 2 Cohort 7: TAK-925 5 mg n = 6
Value	1	1	1	1	1	1	2	1	3	5	0	3	1	0	4	1	0

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

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

Time frame: Baseline up to Day 7. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1-2: Pooled Placebo n = 11	Part 1 Cohort 1: TAK-925 7 mg n = 6	Part 1 Cohort 2: TAK-925 14 mg n = 6	Part 1 Cohort 1: TAK-925 28 mg n = 5	Par 1 Cohort 2: TAK-925 56 mg n = 6	Part 1 Cohort 1: TAK-925 112 mg n = 6	Part 1 Cohort 2: TAK-925 134.4 mg n = 6	Part 1 Cohort S1-S2: Pooled Placebo n = 4	Part 1 Cohort S1: TAK-925 180 mg n = 6	Part 1 Cohort S2: TAK-925 240 mg n = 6	Part 1 Cohort 3: Placebo n = 2	Part 1 Cohort 3: TAK-925 112 mg n = 6	Part 1 Cohort 4: TAK-925 112 mg n = 4	Part 2 Cohort 5-7: Pooled Placebo n = 13	Part 2 Cohort 5: TAK-925 44.8 mg n = 4	Part 2 Cohort 6: TAK-925 11.2 mg n = 4	Part 2 Cohort 7: TAK-925 5 mg n = 6
Value	0	0	0	0	0	0	2	0	2	4	0	3	0	0	1	0	0

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

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

Time frame: Baseline up to Day 7. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1-2: Pooled Placebo n = 11	Part 1 Cohort 1: TAK-925 7 mg n = 6	Part 1 Cohort 2: TAK-925 14 mg n = 6	Part 1 Cohort 1: TAK-925 28 mg n = 5	Par 1 Cohort 2: TAK-925 56 mg n = 6	Part 1 Cohort 1: TAK-925 112 mg n = 6	Part 1 Cohort 2: TAK-925 134.4 mg n = 6	Part 1 Cohort S1-S2: Pooled Placebo n = 4	Part 1 Cohort S1: TAK-925 180 mg n = 6	Part 1 Cohort S2: TAK-925 240 mg n = 6	Part 1 Cohort 3: Placebo n = 2	Part 1 Cohort 3: TAK-925 112 mg n = 6	Part 1 Cohort 4: TAK-925 112 mg n = 4	Part 2 Cohort 5-7: Pooled Placebo n = 13	Part 2 Cohort 5: TAK-925 44.8 mg n = 4	Part 2 Cohort 6: TAK-925 11.2 mg n = 4	Part 2 Cohort 7: TAK-925 5 mg n = 6
Value	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

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

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

Time frame: Baseline up to Day 7. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1-2: Pooled Placebo n = 11	Part 1 Cohort 1: TAK-925 7 mg n = 6	Part 1 Cohort 2: TAK-925 14 mg n = 6	Part 1 Cohort 1: TAK-925 28 mg n = 5	Par 1 Cohort 2: TAK-925 56 mg n = 6	Part 1 Cohort 1: TAK-925 112 mg n = 6	Part 1 Cohort 2: TAK-925 134.4 mg n = 6	Part 1 Cohort S1-S2: Pooled Placebo n = 4	Part 1 Cohort S1: TAK-925 180 mg n = 6	Part 1 Cohort S2: TAK-925 240 mg n = 6	Part 1 Cohort 3: Placebo n = 2	Part 1 Cohort 3: TAK-925 112 mg n = 6	Part 1 Cohort 4: TAK-925 112 mg n = 4	Part 2 Cohort 5-7: Pooled Placebo n = 13	Part 2 Cohort 5: TAK-925 44.8 mg n = 4	Part 2 Cohort 6: TAK-925 11.2 mg n = 4	Part 2 Cohort 7: TAK-925 5 mg n = 6
Value	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0

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

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 7 days (Day 7) after the last dose of study drug. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 Cohort 1-2: Pooled Placebo	0 of 11 (0%)	1 of 11 (9.1%)	0 of 11
Part 1 Cohort 1: TAK-925 7 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 Cohort 2: TAK-925 14 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 Cohort 1: TAK-925 28 mg	0 of 5 (0%)	1 of 5 (20%)	0 of 5
Par 1 Cohort 2: TAK-925 56 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 Cohort 1: TAK-925 112 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 Cohort 2: TAK-925 134.4 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1 Cohort S1-S2: Pooled Placebo	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Part 1 Cohort S1: TAK-925 180 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1 Cohort S2: TAK-925 240 mg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part 1 Cohort 3: Placebo	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Part 1 Cohort 3: TAK-925 112 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1 Cohort 4: TAK-925 112 mg	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Part 2 Cohort 5-7: Pooled Placebo	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Part 2 Cohort 5: TAK-925 44.8 mg	0 of 4 (0%)	4 of 4 (100%)	0 of 4
Part 2 Cohort 6: TAK-925 11.2 mg	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Part 2 Cohort 7: TAK-925 5 mg	0 of 6 (0%)	0 of 6 (0%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Takeda

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-925 in people with Healthy Participants and Patients With Narcolepsy, run by Takeda at 3 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline up to Day 7). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03332784.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2021.