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

Study Description

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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.

Study Design

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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 16, 2018
Estimated Primary Completion Date :	October 31, 2018
Estimated Study Completion Date :	November 17, 2018

Arms and Interventions

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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 orally, 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.

Outcome Measures

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Primary Outcome Measures :

1. Latency in MWT [ Time Frame: Day 1 ]
   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 are 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.

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 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 ]
10. Sleepiness on the Karolinska Sleepiness Scale (KSS) [ Time Frame: Day 1 ]
    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 better results.

Eligibility Criteria

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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).

Contacts and Locations

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Locations

United States, Utah
PRA Health Sciences
Salt Lake City, Utah, United States, 84124

Sponsors and Collaborators

Takeda

Investigators

Study Director:	Medical Director	Takeda

More Information

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Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT03522506 History of Changes
Other Study ID Numbers:	TAK-925-1002; U1111-1211-2133 ( Other Identifier: WHO )
First Posted:	May 11, 2018
Last Update Posted:	October 8, 2018
Last Verified:	October 2018

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:

Modafinil; Armodafinil; Wakefulness-Promoting Agents; Central Nervous System Stimulants	Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs