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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1211-2133 | Other Identifier | WHO |
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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.
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 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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-925 | Drug | TAK-925 intravenous infusion. |
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| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Health Sciences | Salt Lake City | Utah | 84124 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36934366 | Derived | 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. |
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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.
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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.
Healthy sleep deprived participants were enrolled in 1 of the 4 treatment sequences of this 4-period crossover study to receive: TAK 925 44 milligram (mg) (Low dose), TAK-925 112 mg (High dose), modafinil 300 mg, and placebo.
Participants took part in the study at 1 investigative site in the United States from 09 May 2018 to 07 November 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | TAK-925 44 mg + Placebo + TAK-925 112 mg + Modafinil 300 mg | TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 4. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (2 Days) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 8, 2018 | Nov 6, 2019 |
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| 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. |
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| TAK-925 Placebo | Drug | TAK-925 placebo-matching given as saline intravenous infusion. |
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| Modafinil | Drug | Modafinil tablets. |
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| Modafinil Placebo | Drug | Modafinil placebo-matching tablet. |
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| 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 |
| 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 |
| FG001 | TAK-925 112 mg + TAK-925 44 mg + Modafinil 300 mg + Placebo | TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Treatment Period 4. |
| FG002 | Modafinil 300 mg + TAK-925 112 mg + Placebo + TAK-925 44 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 4. |
| FG003 | Placebo + Modafinil 300 mg + TAK-925 44 mg + TAK-925 112 mg | Placebo, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 4. |
| COMPLETED |
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| NOT COMPLETED |
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| Washout Period 1 (7 Days) |
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| Treatment Period 2 (2 Days) |
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| Washout Period 2 (7 Days) |
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| Treatment Period 3 (2 Days) |
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| Washout Period 3 (7 Days) |
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| Treatment Period 4 (2 Days) |
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The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | TAK-925 44 mg + Placebo + TAK-925 112 mg + Modafinil 300 mg | TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 4. |
| BG001 | TAK-925 112 mg + TAK-925 44 mg + Modafinil 300 mg + Placebo | TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Treatment Period 4. |
| BG002 | Modafinil 300 mg + TAK-925 112 mg + Placebo + TAK-925 44 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by placebo once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 4. |
| BG003 | Placebo + Modafinil 300 mg + TAK-925 44 mg + TAK-925 112 mg | Placebo, once on Day 1 of Treatment Period 1, followed by a minimum of 7-days washout period, further followed by modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 2, followed by a minimum of 7-days washout period, further followed by TAK-925 44 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 3, followed by a minimum of 7-days washout period, further followed by TAK-925 112 mg, injection, intravenously, administered as 9-hour infusion, once on Day 1 of Treatment Period 4. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
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| Height | Mean | Standard Deviation | centimeter (cm) |
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| Body mass index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pharmacodynamics (PD) analysis set: all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from MWT, polysomnography (PSG), Karolinska Sleepiness Scale (KSS), or Cambridge Cognition Computerized Battery of Tests (CCBT). PD analysis set where data at specified time points was available. | Posted | Least Squares Mean | Standard Error | minute | Day 1: 2 hours post-infusion start |
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| Secondary | 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 | The pharmacokinetic (PK) analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M-I and M-II | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. The PK analysis set where data at specified time points was available. | Posted | Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M-I and M-II | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-925 and Its Metabolites M-I and M-II | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Mean | Standard Deviation | ng/mL | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M-I and M-II | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | T1/2z: Terminal Disposition Phase Half-life for TAK-925 and Its Metabolites M-I and M-II | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. The PK analysis set where data at specified time points was available. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | CL: Total Clearance After Intravenous Administration for TAK-925 | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Mean | Standard Deviation | liter per hour (L/h) | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-925 | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Mean | Standard Deviation | liter | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | The PK analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 measurable plasma concentration. | Posted | Mean | Standard Deviation | liter | Day 1 pre-dose and at multiple time points (up to 9 hours) post-dose |
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| Secondary | 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. | The PD analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from the MWT, PSG, KSS, or CCBT. The PD analysis set where data at specified time points was available. | Posted | Least Squares Mean | Standard Error | unit on a scale | 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 |
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| Primary | 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. | The PD analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from the MWT, PSG, KSS, or CCBT. The PD analysis set where data at specified time points was available. | Posted | Least Squares Mean | Standard Error | minute | Day 1: 4 hours post-infusion start |
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| Primary | 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. | The PD analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from the MWT, PSG, KSS, or CCBT. The PD analysis set where data at specified time points was available. | Posted | Least Squares Mean | Standard Error | minute | Day 1: 6 hours post-infusion start |
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| Primary | 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. | The PD analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from the MWT, PSG, KSS, or CCBT. The PD analysis set where data at specified time points was available. | Posted | Least Squares Mean | Standard Error | minute | Day 1: 8 hours post-infusion start |
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| Primary | 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. | The PD analysis set consisted of all participants who received at least 1 dose of study drug and have at least 1 evaluable postdose PD endpoint derived from the MWT, PSG, KSS, or CCBT. The PD analysis set where data at specified time points was available. | Posted | Least Squares Mean | Standard Error | minute | Day 1: 1 hour post-end of infusion |
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Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 7 days after the last dose of study drug in Treatment Period 4 (Day 1 up to Day 36)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo, once on Day 1 of Treatment Period 1, 2, 3, or 4. | 0 | 20 | 0 | 20 | 4 | 20 |
| EG001 | TAK-925 44 mg | TAK-925 44 mg, intravenously, injection, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, 2, 3, or 4. | 0 | 18 | 0 | 18 | 5 | 18 |
| EG002 | TAK-925 112 mg | TAK-925 112 mg, intravenously, injection, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, 2, 3, or 4. | 0 | 18 | 0 | 18 | 11 | 18 |
| EG003 | Modafinil 300 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, 2, 3, or 4. | 0 | 19 | 0 | 19 | 11 | 19 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctivitis allergic | Eye disorders | MedDRA (21.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Discomfort | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Feeling jittery | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Feeling of relaxation | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Liver function test increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Muscle contractions involuntary | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Hypervigilance | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Euphoric mood | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
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| Urine odour abnormal | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
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| Skin discomfort | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 29, 2018 | Nov 6, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000729607 | TAK-925 |
| D000077408 | Modafinil |
| ID | Term |
|---|---|
| D001559 | Benzhydryl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Linear mixed effect model | <0.001 | LSM difference | 24.35 | 2-Sided | 95 | 17.64 | 31.06 | Superiority | The effect of TAK-925 was evaluated with a linear mixed effects model appropriate for a 4-period crossover study. The LSM sleep latency for each treatment and the associated standard error and 95% CI was estimated from the model at each time, along with differences between active treatments and placebo, and associated standard errors, 95% CIs, and p-values. |
| Linear mixed effects model | <0.001 | LSM Difference | 19.89 | 2-Sided | 95 | 13.30 | 26.49 | Superiority | The effect of TAK-925 was evaluated with a linear mixed effects model appropriate for a 4-period crossover study. The LSM sleep latency for each treatment and the associated standard error and 95% CI was estimated from the model at each time, along with differences between active treatments and placebo, and associated standard errors, 95% CIs, and p-values. |
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| OG003 | Modafinil 300 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Intervention Periods 1 to 4. |
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| OG002 |
| TAK-925 112 mg |
TAK-925 112 mg, intravenously, injection, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
| OG003 | Modafinil 300 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
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|
| OG002 |
| TAK-925 112 mg |
TAK-925 112 mg, intravenously, injection, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
| OG003 | Modafinil 300 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
|
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|
| OG002 |
| TAK-925 112 mg |
TAK-925 112 mg, intravenously, injection, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
| OG003 | Modafinil 300 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
|
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|
| OG002 |
| TAK-925 112 mg |
TAK-925 112 mg, intravenously, injection, administered as 9-hour infusion, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
| OG003 | Modafinil 300 mg | Modafinil 300 mg, tablet, orally, once on Day 1 of Treatment Period 1, 2, 3, or 4. |
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