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

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ClinicalTrials.gov Identifier: NCT03522506
Recruitment Status : Completed
First Posted : May 11, 2018
Results First Posted : November 26, 2019
Last Update Posted : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief 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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: TAK-925 Drug: TAK-925 Placebo Drug: Modafinil Drug: Modafinil Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
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
Actual Study Start Date : May 9, 2018
Actual Primary Completion Date : November 7, 2018
Actual Study Completion Date : November 7, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Modafinil

Arm Intervention/treatment
Experimental: TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil
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.
Drug: TAK-925
TAK-925 intravenous infusion.

Drug: TAK-925 Placebo
TAK-925 placebo-matching given as saline intravenous infusion.

Drug: Modafinil
Modafinil tablets.

Drug: Modafinil Placebo
Modafinil placebo-matching tablet.

Experimental: TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo
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.
Drug: TAK-925
TAK-925 intravenous infusion.

Drug: TAK-925 Placebo
TAK-925 placebo-matching given as saline intravenous infusion.

Drug: Modafinil
Modafinil tablets.

Drug: Modafinil Placebo
Modafinil placebo-matching tablet.

Experimental: Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose
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.
Drug: TAK-925
TAK-925 intravenous infusion.

Drug: TAK-925 Placebo
TAK-925 placebo-matching given as saline intravenous infusion.

Drug: Modafinil
Modafinil tablets.

Drug: Modafinil Placebo
Modafinil placebo-matching tablet.

Experimental: Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose
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.
Drug: TAK-925
TAK-925 intravenous infusion.

Drug: TAK-925 Placebo
TAK-925 placebo-matching given as saline intravenous infusion.

Drug: Modafinil
Modafinil tablets.

Drug: Modafinil Placebo
Modafinil placebo-matching tablet.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  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 M-I and M-II [ Time Frame: Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Be willing to have actigraphy monitoring during the week before randomization and in each interval.

Exclusion Criteria:

  1. Has a positive alcohol or drug screen.
  2. 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).
  3. 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.
  4. 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.
  5. Abnormal findings on the initial polysomnography (PSG) conducted on Day -1 (check-in), as specified in the study manual.
  6. Traveled across 2 or more time zones 2 weeks or less before screening.
  7. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03522506


Locations
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United States, Utah
PRA Health Sciences
Salt Lake City, Utah, United States, 84124
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Takeda
  Study Documents (Full-Text)

Documents provided by Takeda:
Study Protocol  [PDF] March 8, 2018
Statistical Analysis Plan  [PDF] November 29, 2018

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03522506    
Other Study ID Numbers: TAK-925-1002
U1111-1211-2133 ( Other Identifier: WHO )
First Posted: May 11, 2018    Key Record Dates
Results First Posted: November 26, 2019
Last Update Posted: November 26, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
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Modafinil
Central Nervous System Stimulants
Physiological Effects of Drugs
Wakefulness-Promoting Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action