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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TAK-925
* Drug: TAK-925 Placebo
* Drug: Modafinil
* Drug: Modafinil Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-925 Low Dose + Placebo + TAK-925 High Dose + Modafinil<br>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<br>* TAK-925 intravenous infusion.<br>Drug: TAK-925 Placebo<br>* TAK-925 placebo-matching given as saline intravenous infusion.<br>Drug: Modafinil<br>* Modafinil tablets.<br>Drug: Modafinil Placebo<br>* Modafinil placebo-matching tablet.<br>|
| Experimental: TAK-925 High Dose + TAK-925 Low Dose + Modafinil + Placebo<br>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<br>* TAK-925 intravenous infusion.<br>Drug: TAK-925 Placebo<br>* TAK-925 placebo-matching given as saline intravenous infusion.<br>Drug: Modafinil<br>* Modafinil tablets.<br>Drug: Modafinil Placebo<br>* Modafinil placebo-matching tablet.<br>|
| Experimental: Modafinil + TAK-925 High Dose + Placebo + TAK-925 Low Dose<br>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<br>* TAK-925 intravenous infusion.<br>Drug: TAK-925 Placebo<br>* TAK-925 placebo-matching given as saline intravenous infusion.<br>Drug: Modafinil<br>* Modafinil tablets.<br>Drug: Modafinil Placebo<br>* Modafinil placebo-matching tablet.<br>|
| Experimental: Placebo + Modafinil + TAK-925 Low Dose + TAK-925 High Dose<br>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<br>* TAK-925 intravenous infusion.<br>Drug: TAK-925 Placebo<br>* TAK-925 placebo-matching given as saline intravenous infusion.<br>Drug: Modafinil<br>* Modafinil tablets.<br>Drug: Modafinil Placebo<br>* Modafinil placebo-matching tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | Day 1: 1 hour post-end of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose | 
| CL: Total Clearance After Intravenous Administration for TAK-925 |  | 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 |  | 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 |  | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy