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

• ClinicalTrials.gov Identifier: NCT03522506
• Recruitment Status: Completed
• First Posted: May 11, 2018
• Results First Posted: November 26, 2019
• Last Update Posted: March 26, 2021
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

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

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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

Locations

United States, Utah

PRA Health Sciences

Salt Lake City, Utah, United States, 84124

Sponsors and Collaborators

Takeda

Investigators

• 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

More Information

• 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
• Results First Posted: November 26, 2019
• Last Update Posted: March 26, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• 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; 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