Healthy VolunteersPhase 1NCT03522506

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of TAK-925 Study in Sleep-Deprived Healthy Adults

A Phase 1 study testing TAK-925 and Modafinil in people with Healthy Volunteers, run by Takeda at 1 site in United States.

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 determine the effect of TAK-925 after a single intravenous dose (compared to placebo) on promoting wakefulness as measured by sleep latency on the maintenance of wakefulness (MWT) in sleep-deprived healthy participants. Read more about this study

Who is it for?: Ages 18 to 40 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: TAK-925 and Modafinil
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 9 May 2018to 7 Nov 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 40 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Be a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before study drug administration of the initial dose of study drug.
Have regular sleep-wake habits (example, routinely spending 6.5 to 8 hours sleeping nightly, not oversleeping by more than 3 hours on weekends, that is, total sleep not more than 11 hours) as determined by investigator interviews and confirmed in 5-day actigraphy records and whom regularly fall asleep between 9:30 PM and 12:00 AM.
Be willing to have actigraphy monitoring during the week before randomization and in each interval.

Who cannot join

Has a positive alcohol or drug screen.
Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer [354 milliliter per (mL/)12 ounces], wine (118 mL/4 ounces), or distilled spirits (29.5 mL/1 ounce)] per day).
Has excessive sleepiness defined by a self-reported Epworth Sleepiness Scale score at screening greater than 10; irregular work hours; or routine night-shift work within 1 month before randomization.
Currently experiencing or having a history of any known/suspected sleep disorder, any disorder associated with excessive daytime somnolence (EDS), or any diagnosis interfering with assessment of sleepiness.
Abnormal findings on the initial polysomnography (PSG) conducted on Day -1 (check-in), as specified in the study manual.
Traveled across 2 or more time zones 2 weeks or less before screening.
Caffeine consumption of more than 400 milligram per day (mg/day) for 2 weeks before screening (1 serving of coffee is approximately equivalent to 120 mg of caffeine).

Trial locations and contacts

1 site in 1 country.

United States1 site

PRA Health Sciences
Salt Lake City, Utah, 84124

Other trials in United States

About this study

Official title: A Phase 1b, 4-Period Crossover, Placebo-Controlled, Randomized, Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-925 in Sleep-Deprived Healthy Adults Utilizing Modafinil as an Active Comparator

Read the detailed description

The drug being tested in this study is called TAK-925. This study will assess the safety, tolerability, PK and PD of TAK-925 and will assess the effects of TAK-925 in sleep-deprived healthy adult participants.

The study will enroll approximately 20 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 4 treatment sequences-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo
Modafinil+ TAK-925 High Dose + Placebo + TAK-925 Low Dose
Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose

TAK-925 will be administered as an intravenous infusion based on the availability of safety, tolerability and PK data from health Japanese participants in ongoing study TAK-925-1001.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 10 weeks. Participants will make a final visit 7 days after receiving their last dose of drug for a follow-up assessment.

Conditions: Healthy Volunteers
Being tested: TAK-925, TAK-925 Placebo, Modafinil, Modafinil Placebo
Keywords: Drug Therapy

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.
TAK-925 PlaceboDrug
TAK-925 placebo-matching given as saline intravenous infusion.
ModafinilDrug
Modafinil tablets.
Modafinil PlaceboDrug
Modafinil placebo-matching tablet.

Study groups in NCT03522506
Study group	Role	What they receive
TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil	Experimental	TAK-925 low dose milligram (mg), intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001. Receives: Drug: TAK-925; Drug: TAK-925 Placebo; Drug: Modafinil; Drug: Modafinil Placebo
TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo	Experimental	TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 low dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001. Receives: Drug: TAK-925; Drug: TAK-925 Placebo; Drug: Modafinil; Drug: Modafinil Placebo
Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose	Experimental	Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 low dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001. Receives: Drug: TAK-925; Drug: TAK-925 Placebo; Drug: Modafinil; Drug: Modafinil Placebo
Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose	Experimental	Placebo, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 low dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001. Receives: Drug: TAK-925; Drug: TAK-925 Placebo; Drug: Modafinil; Drug: Modafinil Placebo

What is being measured

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

Latency to Sleep Onset on Maintenance of Wakefulness Test (MWT) at 2 Hours Post-infusion Start
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: Day 1: 2 hours post-infusion start
Latency to Sleep Onset on MWT at 4 Hours Post-infusion Start
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: Day 1: 4 hours post-infusion start
Latency to Sleep Onset on MWT at 6 Hours Post-infusion Start
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: Day 1: 6 hours post-infusion start
Latency to Sleep Onset on MWT at 8 Hours Post-infusion Start
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: Day 1: 8 hours post-infusion start
Latency to Sleep Onset on MWT at 1 Hour Post-end 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.
Measured: Day 1: 1 hour post-end of infusion

Secondary outcomes (10)

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 M-I and M-II
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M-I and M-II
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M-I and M-II
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-925 and Its Metabolites M-I and M-II
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M-I and M-II
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
T1/2z: Terminal Disposition Phase Half-life for TAK-925 and Its Metabolites M-I and M-II
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
CL: Total Clearance After Intravenous Administration for TAK-925
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-925
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
Measured: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Sleepiness on KSS
The KSS scale measures the subjective level of sleepiness at a particular time during the day. On this scale participants indicate which level best reflects the psycho-physical state experienced in the last 10 minutes. The KSS is a 9-item Likert-type rating scale for assessing subjective sleepiness, where 1=very alert, 3=alert, 5=neither alert nor sleepy, 7=sleepy (but not fighting sleep), 9=very sleepy (fighting sleep). Lower score indicates more alertness.
Measured: Day 1: 14, 10, 6, 2 hours pre-infusion; 2.75, 4.75, 6.75. 8.75 hours post-infusion start; 1.75 hours post-infusion end

Timeline

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

9 May 20187 Nov 2018

First posted11 May 2018
Study start9 May 2018
Primary completion7 Nov 2018
Study completion7 Nov 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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies 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: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03522506
Sponsor's protocol ID: TAK-925-1002
Other IDs: U1111-1211-2133
Status last verified: Mar 2021
First submitted: 30 Apr 2018
Last updated: 26 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
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.

Publications

Evans R, Kimura H, Nakashima M, Ishikawa T, Yukitake H, Suzuki M, Hazel J, Faessel H, Wu J, Hang Y, Alexander R, Rosen L, Hartman DS, Ratti E. Orexin 2 receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals. J Sleep Res. 2023 Oct;32(5):e13878. doi: 10.1111/jsr.13878. Epub 2023 Mar 19.
PubMed 36934366

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b, 4-Period Crossover, Placebo-Controlled, Randomized, Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-925 in Sleep-Deprived Healthy Adults Utilizing Modafinil as an Active Comparator
ClinicalTrials.gov ID: NCT03522506
Acronym / sponsor ID: TAK-925-1002
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 9 May 2018 (actual)
Primary completion: 7 Nov 2018 (actual)
Study completion: 7 Nov 2018 (actual)
First posted: 11 May 2018 (actual)
Results: Posted 26 Nov 2019

Clinical summary

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

Detailed description

TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo
Modafinil+ TAK-925 High Dose + Placebo + TAK-925 Low Dose
Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose

TAK-925 will be administered as an intravenous infusion based on the availability of safety, tolerability and PK data from health Japanese participants in ongoing study TAK-925-1001.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil	Experimental	Drug: TAK-925, Drug: TAK-925 Placebo, Drug: Modafinil, Drug: Modafinil PlaceboTAK-925 low dose milligram (mg), intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001.
TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo	Experimental	Drug: TAK-925, Drug: TAK-925 Placebo, Drug: Modafinil, Drug: Modafinil PlaceboTAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 low dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001.
Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose	Experimental	Drug: TAK-925, Drug: TAK-925 Placebo, Drug: Modafinil, Drug: Modafinil PlaceboModafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 low dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001.
Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose	Experimental	Drug: TAK-925, Drug: TAK-925 Placebo, Drug: Modafinil, Drug: Modafinil PlaceboPlacebo, once on Day 1 of Intervention Period 1, followed by a minimum of 7-days washout period, further followed by Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 low dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 high dose mg, intravenously, administered as 9-hour infusion, once on Day 1 of Intervention Period 4. TAK-925 dose will be decided based on the availability of safety, tolerability and PK data from ongoing study TAK-925-1001.

Who may qualify

Ages: 18 to 40 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Be a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before study drug administration of the initial dose of study drug.
Have regular sleep-wake habits (example, routinely spending 6.5 to 8 hours sleeping nightly, not oversleeping by more than 3 hours on weekends, that is, total sleep not more than 11 hours) as determined by investigator interviews and confirmed in 5-day actigraphy records and whom regularly fall asleep between 9:30 PM and 12:00 AM.
Be willing to have actigraphy monitoring during the week before randomization and in each interval.

Key exclusion criteria (7 listed)

Has a positive alcohol or drug screen.
Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer [354 milliliter per (mL/)12 ounces], wine (118 mL/4 ounces), or distilled spirits (29.5 mL/1 ounce)] per day).
Has excessive sleepiness defined by a self-reported Epworth Sleepiness Scale score at screening greater than 10; irregular work hours; or routine night-shift work within 1 month before randomization.
Currently experiencing or having a history of any known/suspected sleep disorder, any disorder associated with excessive daytime somnolence (EDS), or any diagnosis interfering with assessment of sleepiness.
Abnormal findings on the initial polysomnography (PSG) conducted on Day -1 (check-in), as specified in the study manual.

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	Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose, Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose, TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo, TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
TAK-925 PlaceboTAK-925 placebo-matching given as saline intravenous infusion.	Drug	Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose, Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose, TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo, TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
ModafinilModafinil tablets.	Drug	Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose, Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose, TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo, TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
Modafinil PlaceboModafinil placebo-matching tablet.	Drug	Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose, Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose, TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo, TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil

Primary outcome

Latency to Sleep Onset on Maintenance of Wakefulness Test (MWT) at 2 Hours Post-infusion Start
Time frame: Day 1: 2 hours post-infusion start
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.
Latency to Sleep Onset on MWT at 4 Hours Post-infusion Start
Time frame: Day 1: 4 hours post-infusion start
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.
Latency to Sleep Onset on MWT at 6 Hours Post-infusion Start
Time frame: Day 1: 6 hours post-infusion start
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.
Latency to Sleep Onset on MWT at 8 Hours Post-infusion Start
Time frame: Day 1: 8 hours post-infusion start
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.
Latency to Sleep Onset on MWT at 1 Hour Post-end of Infusion
Time frame: Day 1: 1 hour post-end 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.

10 secondary outcomes

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 M-I and M-II
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M-I and M-II
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M-I and M-II
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-925 and Its Metabolites M-I and M-II
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M-I and M-II
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
T1/2z: Terminal Disposition Phase Half-life for TAK-925 and Its Metabolites M-I and M-II
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
CL: Total Clearance After Intravenous Administration for TAK-925
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-925
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
Time frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose
Sleepiness on KSS
Time frame: Day 1: 14, 10, 6, 2 hours pre-infusion; 2.75, 4.75, 6.75. 8.75 hours post-infusion start; 1.75 hours post-infusion end

Results and safety

Results posted to the registry on 26 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TAK-925 44 mg + Placebo + TAK-925 112 mg + Modafinil 300 mg	5	5
TAK-925 112 mg + TAK-925 44 mg + Modafinil 300 mg + Placebo	5	5
Modafinil 300 mg + TAK-925 112 mg + Placebo + TAK-925 44 mg	5	5
Placebo + Modafinil 300 mg + TAK-925 44 mg + TAK-925 112 mg	5	5

Primary outcome: Latency to Sleep Onset on Maintenance of Wakefulness Test (MWT) at 2 Hours Post-infusion Start

Time frame: Day 1: 2 hours post-infusion start. Least squares mean (Standard Error). Unit: minute

Measure	Placebo n = 20	TAK-925 44 mg n = 18	TAK-925 112 mg n = 18	Modafinil 300 mg n = 19
Value	15.68 (2.305)	35.74 (2.445)	40.02 (2.445)	35.57 (2.368)

Placebo vs TAK-925 44 mg: Least square mean difference: 20.06 (95% CI 13.35 to 26.77), p <0.001, Linear mixed effect model
Placebo vs TAK-925 112 mg: LSM difference: 24.35 (95% CI 17.64 to 31.06), p <0.001, Linear mixed effect model
Placebo vs Modafinil 300 mg: LSM Difference: 19.89 (95% CI 13.30 to 26.49), p <0.001, Linear mixed effects model

Population analysed: Pharmacodynamics (PD) analysis set: all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from MWT, polysomnography (PSG), Karolinska Sleepiness Scale (KSS), or Cambridge Cognition Computerized Battery of Tests (CCBT). PD analysis set where data at specified time points was available.

Primary outcome: Latency to Sleep Onset on MWT at 4 Hours Post-infusion Start

Time frame: Day 1: 4 hours post-infusion start. Least squares mean (Standard Error). Unit: minute

Measure	Placebo n = 20	TAK-925 44 mg n = 18	TAK-925 112 mg n = 18	Modafinil 300 mg n = 19
Value	9.10 (2.186)	32.04 (2.320)	40.05 (2.320)	35.60 (2.246)

Placebo vs TAK-925 44 mg: LSM difference: 22.94 (95% CI 16.58 to 29.30), p <0.001, Linear mixed effect model
Placebo vs TAK-925 112 mg: LSM difference: 30.95 (95% CI 24.59 to 37.31), p <0.001, Linear mixed effects model
Placebo vs Modafinil 300 mg: LSM difference: 26.50 (95% CI 20.24 to 32.75), p <0.001, Linear mixed effect model

Population analysed: The PD analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from the MWT, PSG, KSS, or CCBT. The PD analysis set where data at specified time points was available.

Primary outcome: Latency to Sleep Onset on MWT at 6 Hours Post-infusion Start

Time frame: Day 1: 6 hours post-infusion start. Least squares mean (Standard Error). Unit: minute

Measure	Placebo n = 20	TAK-925 44 mg n = 18	TAK-925 112 mg n = 18	Modafinil 300 mg n = 19
Value	6.15 (2.589)	20.71 (2.742)	38.36 (2.742)	31.89 (2.659)

Placebo vs TAK-925 44 mg: LSM difference: 14.56 (95% CI 7.04 to 22.08), p <0.001, Linear mixed effect model
Placebo vs TAK-925 112 mg: LSM difference: 32.21 (95% CI 24.68 to 39.73), p <0.001, Linear mixed effect model
Placebo vs Modafinil 300 mg: LSM difference: 25.74 (95% CI 18.33 to 33.14), p <0.001, Linear mixed effect model

Primary outcome: Latency to Sleep Onset on MWT at 8 Hours Post-infusion Start

Time frame: Day 1: 8 hours post-infusion start. Least squares mean (Standard Error). Unit: minute

Measure	Placebo n = 20	TAK-925 44 mg n = 18	TAK-925 112 mg n = 18	Modafinil 300 mg n = 19
Value	3.53 (2.146)	13.13 (2.279)	36.86 (2.279)	20.44 (2.206)

Placebo vs TAK-925 44 mg: LSM difference: 9.60 (95% CI 3.35 to 15.85), p = 0.003, Linear mixed effect model
Placebo vs TAK-925 112 mg: LSM difference: 33.33 (95% CI 27.08 to 39.58), p <0.001, Linear mixed effect model
Placebo vs Modafinil 300 mg: LSM difference: 16.91 (95% CI 10.77 to 23.06), p <0.001, Linear mixed effect model

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 7 days after the last dose of study drug in Treatment Period 4 (Day 1 up to Day 36). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 20 (0%)	4 of 20 (20%)	0 of 20
TAK-925 44 mg	0 of 18 (0%)	5 of 18 (27.8%)	0 of 18
TAK-925 112 mg	0 of 18 (0%)	11 of 18 (61.1%)	0 of 18
Modafinil 300 mg	0 of 19 (0%)	11 of 19 (57.9%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36934366Evans R, Kimura H, Nakashima M, Ishikawa T, Yukitake H, Suzuki M, Hazel J, Faessel H, Wu J, Hang Y, Alexander R, Rosen L, Hartman DS, Ratti E. Orexin 2 receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals. J Sleep Res. 2023 Oct;32(5):e13878. doi: 10.1111/jsr.13878. Epub 2023 Mar 19.
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.

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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.

Medical Director study director

Takeda

1 site 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 and Modafinil in people with Healthy Volunteers, run by Takeda at 1 site in United States.

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 3 inclusion and 7 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 26 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 1 site in United States. 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. 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 26 Nov 2019). 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?

Latency to Sleep Onset on Maintenance of Wakefulness Test (MWT) at 2 Hours Post-infusion Start (time frame: Day 1: 2 hours post-infusion start). The study lists 5 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 NCT03522506, which also lists 1 linked publication.

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 26 Mar 2021.