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

NCT03522506 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-925-1002U1111-1211-2133
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (5)

• 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 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

  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

Study Arms (4)

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.

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.

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.

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.

Drug: TAK-925; Drug: TAK-925 Placebo; Drug: Modafinil; Drug: Modafinil Placebo

Interventions

TAK-925 DRUG

TAK-925 intravenous infusion.

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 Placebo DRUG

TAK-925 placebo-matching given as saline intravenous infusion.

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 DRUG

Modafinil tablets.

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 Placebo DRUG

Modafinil placebo-matching tablet.

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

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

PRA Health Sciences

Salt Lake City, Utah, 84124, United States

Location

Related Publications (1)

• 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.

  PMID: 36934366 DERIVED

MeSH Terms

Interventions

TAK-925; Modafinil

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Medical director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: May 11, 2018
• Study Start: May 9, 2018
• Primary Completion: November 7, 2018
• Study Completion: November 7, 2018
• Last Updated: March 26, 2021
• Results First Posted: November 26, 2019

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (1)