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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1201-6634 | Other Identifier | WHO | |
| JapicCTI-173756 | Registry Identifier | JapicCTI |
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The purpose of this study is to investigate safety, tolerability, and pharmacokinetics of TAK-925 when a single dose of TAK-925 is administered to healthy adult participants, healthy elderly participants and patients with type 1 narcolepsy.
Orexins are neuropeptides that play a role in the regulation of sleep and wakefulness. In type 1 narcolepsy, there is a loss of orexin producing neurons in the brain. The investigational drug, TAK-925, is an orexin 2 receptor agonist that is being tested in healthy adult participants, healthy elderly participants and patients with narcolepsy in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single intravenous administration.
The study will enroll approximately 20 healthy participants and 16 healthy elderly participants in Part 1 of the study and approximately 20 patients with narcolepsy in Part 2.
In Part 1, the study consists of 4 cohorts of 8 or 4 participants each. Participants will be randomly assigned (by chance, like flipping a coin) to one of the following treatment groups to receive TAK-925 or placebo:
- Part 1, Cohort 1; TAK-925 (Dose Level 1, 3, 5), Cohort 2; TAK-925 (Dose Level 2, 4, 6), Cohort 3 and 4; TAK-925 (Dose Level 5)
For Cohort 1-4, healthy adult and elderly participants will be administered TAK-925 or placebo once in each cohort or dose level. The dose at the start (Cohort 1 dose level 1) is 7 mg of TAK-925 and following doses in Cohorts 1-4 will be determined based on available data from previous Cohorts/dose levels.
In Part 2 of the study, the study consists of 3 cohorts of 4 to 12 patients with narcolepsy. Patients will be randomly assigned to one of the treatment groups of Cohort 5-7 and will be administered TAK-925 or placebo once in each cohort. The dose of TAK-925 in Cohort 5-7 is TBD and will be decided based on available data from Part 1 and previous Cohorts.
- Part 2, Cohort 5-7
This multi-center trial will be conducted in Japan. Participants will make multiple visits to the clinic. Visits in Part 1 will include a screening period (Day -28 to -2), Check-in on Day -1, Treatment period (Day 1 and 2), and follow-up visit on Day 7. In Part 2 of the study, the visits include a screening period (Day -42 to -2), Check-in on Day -1, Cross-over period (Day 1 to 4), and follow-up visit on Day 7.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: TAK-925 (Cohort 1; Dose Level 1) | Experimental | TAK-925, Intravenous single administration. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 2; Dose Level 2) | Experimental | TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 2). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 1; Dose Level 3) | Experimental | TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 3). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 2; Dose Level 4) | Experimental | TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 4). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 1; Dose Level 5) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-925 | Drug | TAK-925 Intravenous Infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 7 | |
| Number of Participants Who Experience at Least One TEAE Related to Vital Signs | Baseline up to Day 7 | |
| Number of Participants Who Experience at Least One TEAE Related to Body Weight | Baseline up to Day 7 | |
| Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG) | Baseline up to Day 7 | |
| Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests | Baseline up to Day 7 | |
| Part 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 M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | |
| Part 2, 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 M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | |
| Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT) | 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. |
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Inclusion Criteria:
Healthy adult participants and Healthy elderly participants:
- Participant weighs at least 50 kilogram (kg) (Healthy adults participants) / 40 kg (Healthy elderly participants) and has a body mass index (BMI) from 18.5 to 30 kilogram per square meter (kg/m^2), inclusive at Screening.
Narcolepsy patients:
Exclusion Criteria:
All Participants:
HV (only Cohort 4):
- Participant has had CSF collection performed within 14 days prior to check-in (Day -1).
Narcolepsy patients
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sumida Hospital | Sumida-ku | Tokyo | Japan | |||
| Hakata Clinic |
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 adult and elderly participants were enrolled to receive TAK-925 or placebo in Cohorts 1 and 2 under alternating panel design and in Cohorts S1, S2, 3, and 4 under parallel design of Part 1, and participants with type 1 narcolepsy were enrolled to receive TAK-925 or placebo in a 2-period cross-over design in Cohorts 5, 6, and 7 of Part 2.
Participants took part in the study at 3 investigative sites in Japan from 04 November 2017 to 04 September 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + TAK-925 112 mg | TAK-925 7 milligram (mg), infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group A in double-blind, alternating panel. |
| FG001 | Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + Placebo | TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group B in double-blind, alternating panel. |
| FG002 | Part 1 Cohort 1: TAK-925 7 mg + Placebo + TAK-925 112 mg | TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg, infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group C in double-blind, alternating panel. |
| FG003 | Part 1 Cohort 1: Placebo + TAK-925 28 mg + TAK-925 112 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg, infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg, infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group D in double-blind, alternating panel. |
| FG004 | Part 1 Cohort 2:TAK-925 14 mg +TAK-925 56 mg +TAK-925 134.4 mg | TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group E in double-blind, alternating panel. |
| FG005 | Part 1 Cohort 2: TAK-925 14 mg + TAK-925 56 mg + Placebo | TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 3 in Group F in healthy adults in double-blind, alternating panel. |
| FG006 | Part 1 Cohort 2: TAK-925 14 mg + Placebo + TAK-925 134.4 mg | TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group G in double-blind, alternating panel. |
| FG007 | Part 1 Cohort 2: Placebo + TAK-925 56 mg + TAK-925 134.4 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group H in double-blind, alternating panel. |
| FG008 | Part 1 Cohort S1-S2: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| FG009 | Part 1 Cohort S1: TAK-925 180 mg | TAK-925 180 mg, infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| FG010 | Part 1 Cohort S2: TAK-925 240 mg | TAK-925 240 mg, infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| FG011 | Part 1 Cohort 3: Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy elderly participants in double-blind, parallel group. |
| FG012 | Part 1 Cohort 3: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy elderly participants in double-blind, parallel group. |
| FG013 | Part 1 Cohort 4: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy adults in unblinded manner. |
| FG014 | Part 2 Cohort 5: TAK-925 44.8 mg + Placebo | TAK-925 44.8 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group I under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| FG015 | Part 2 Cohort 5: Placebo + TAK-925 44.8 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 44.8 mg, infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group J under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| FG016 | Part 2 Cohort 6: TAK-925 11.2 mg + Placebo | TAK-925 11.2 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group K under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| FG017 | Part 2 Cohort 6: Placebo + TAK-925 11.2 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 11.2 mg, infusion, intravenously, once on Day 1 Period 2 (Day 3) in participants with type 1 narcolepsy in Group L under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| FG018 | Part 2 Cohort 7: TAK-925 5 mg + Placebo | TAK-925 5 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group M under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| FG019 | Part 2 Cohort 7: Placebo + TAK-925 5 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 5 mg, infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group N under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parts 1 and 2 - Period 1 (1 Day) |
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| Parts 1 and 2- Period 2 (1 Day) |
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| Part 1- Period 3 (1 Day) |
|
The safety analysis set was defined as all participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + TAK-925 112 mg | TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group A in double-blind, alternating panel. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 7 days (Day 7) after the last dose of study drug
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1 Cohort 1-2: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy adults in Group A to H in double-blind, alternating panel. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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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 6, 2018 | Sep 2, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 2, 2018 | Oct 26, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000729607 | TAK-925 |
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TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 2; Dose Level 6) | Experimental | TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 6). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: Placebo (Cohort 1-2) | Placebo Comparator | TAK-925 Placebo, Intravenous single administration. Healthy adults will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 3; Dose Level 5) | Experimental | TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy elderly participants will be enrolled in double blind manner. |
|
| Part 1: Placebo (Cohort 3) | Placebo Comparator | TAK-925 Placebo, Intravenous single administration. Healthy elderly participants will be enrolled in double blind manner. |
|
| Part 1: TAK-925 (Cohort 4; Dose Level 5) | Experimental | TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy adults will be enrolled in non-blinded manner. |
|
| Part 2: TAK-925 TBD (Cohort 5) | Experimental | TAK-925, Intravenous single administration. Dose in Cohort 5 will be based on safety and tolerability in the Part 1. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). |
|
| Part 2: TAK-925 TBD (Cohort 6) | Experimental | TAK-925, Intravenous single administration. Dose in Cohort 6 TBD based on safety, tolerability, PK data, and results of the Maintenance Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). |
|
| Part 2: TAK-925 TBD (Cohort 7) | Experimental | TAK-925, Intravenous single administration. Dose in Cohort 7 TBD based on safety, tolerability, PK data, and results of the Maintenance of Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). |
|
| Part 2: Placebo (Cohort 5-7) | Placebo Comparator | TAK-925 Placebo, Intravenous single administration. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open). |
|
| Placebo | Drug | TAK-925 Placebo Intravenous Infusion |
|
| Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, CL: Total Clearance After Intravenous Administration for TAK-925 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
| Part 2, CL: Total Clearance After Intravenous Administration for TAK-925 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
| Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24 | Urine assessments were done only in Part 1, as planned. | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion |
| Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2 | Urine assessments were done only in Part 1, as planned. | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion |
| Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2 | Urine assessments were done only in Part 1, as planned. | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion |
| Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4 | Day 1 at 6 hours after start of infusion |
| Days 1 and 3 up to 8 hours following the start of infusion |
| Fukuoka |
| Japan |
| PS Clinic | Fukuoka | Japan |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 |
| Part 1 Cohort 1: TAK-925 7 mg + TAK-925 28 mg + Placebo |
TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group B in double-blind, alternating panel. |
| BG002 | Part 1 Cohort 1: TAK-925 7 mg + Placebo + TAK-925 112 mg | TAK-925 7 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg, infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group C in double-blind, alternating panel. |
| BG003 | Part 1 Cohort 1: Placebo + TAK-925 28 mg + TAK-925 112 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 28 mg, infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 112 mg, infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group D in double-blind, alternating panel. |
| BG004 | Part 1 Cohort 2:TAK-925 14 mg +TAK-925 56 mg +TAK-925 134.4 mg | TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group E in double-blind, alternating panel. |
| BG005 | Part 1 Cohort 2: TAK-925 14 mg + TAK-925 56 mg + Placebo | TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 3 in Group F in healthy adults in double-blind, alternating panel. |
| BG006 | Part 1 Cohort 2: TAK-925 14 mg + Placebo + TAK-925 134.4 mg | TAK-925 14 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group G in double-blind, alternating panel. |
| BG007 | Part 1 Cohort 2: Placebo + TAK-925 56 mg + TAK-925 134.4 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 56 mg infusion, intravenously, once on Day 1 of Period 2, further followed by TAK-925 134.4 mg infusion, intravenously, once on Day 1 of Period 3 in healthy adults in Group H in double-blind, alternating panel. |
| BG008 | Part 1 Cohort S1-S2: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| BG009 | Part 1: Cohort S1 TAK-925 180 mg | TAK-925 180 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy adults in double-blind, parallel group. |
| BG010 | Part 1: Cohort S2 TAK-925 240 mg | TAK-925 240 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy adults in double-blind, parallel group. |
| BG011 | Part 1: Cohort 3 Placebo | TAK-925 placebo-matching infusion, intravenously, once, over 9 hours on Day 1 in healthy elderly participants in double-blind, parallel group. |
| BG012 | Part 1: Cohort 3 TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy elderly participants in double-blind, parallel group. |
| BG013 | Part 1: Cohort 4 TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once, over 9 hours on Day 1 in healthy adults in unblinded manner. |
| BG014 | Part 2 Cohort 5: TAK-925 44.8 mg + Placebo | TAK-925 44.8 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group I under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| BG015 | Part 2 Cohort 5, Part J: TAK-925 Placebo + 44.8 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 44.8 mg, infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group J under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| BG016 | Part 2 Cohort 6: TAK-925 11.2 mg + Placebo | TAK-925 11.2 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group K under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| BG017 | Part 2 Cohort 6: Placebo + TAK-925 11.2 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 11.2 mg, infusion, intravenously, once on Day 1 Period 2 (Day 3) in participants with type 1 narcolepsy in Group L under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| BG018 | Part 2 Cohort 7: TAK-925 5 mg + Placebo | TAK-925 5 mg, infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group M under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications. |
| BG019 | Part 2 Cohort 7: Placebo + TAK-925 5 mg | TAK-925 placebo-matching infusion, intravenously, once on Day 1 of Period 1, followed by TAK-925 5 mg, infusion, intravenously, once on Day 1 of Period 2 (Day 3) in participants with type 1 narcolepsy in Group N under 2-period crossover design. A washout period of 7 days was required before the dosing on Day 1 for prior medications |
| BG020 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m˄2) |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Smoking Classification | Count of Participants | Participants |
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| Alcohol Classification | Count of Participants | Participants |
|
| Caffeine Classification | Count of Participants | Participants |
|
| OG002 |
| Part 1 Cohort 2: TAK-925 14 mg |
TAK-925 14 mg, infusion, intravenously, once on Day 1 in healthy adults in Group E to H in double-blind, alternating panel. |
| OG003 | Part 1 Cohort 1: TAK-925 28 mg | TAK-925 28 mg, infusion, intravenously, once on Day 1 in healthy adults in Group A to D in double-blind, alternating panel. |
| OG004 | Par 1 Cohort 2: TAK-925 56 mg | TAK-925 56 mg, infusion, intravenously, once on Day 1 in healthy adults in Group E to H in double-blind, alternating panel. |
| OG005 | Part 1 Cohort 1: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy adults in Group A to D in double-blind, alternating panel. |
| OG006 | Part 1 Cohort 2: TAK-925 134.4 mg | TAK-925 134.4 mg, infusion, intravenously, once on Day 1 in healthy adults in Group E to H in double-blind, alternating panel. |
| OG007 | Part 1 Cohort S1-S2: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| OG008 | Part 1 Cohort S1: TAK-925 180 mg | TAK-925 180 mg, infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| OG009 | Part 1 Cohort S2: TAK-925 240 mg | TAK-925 240 mg, infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. |
| OG010 | Part 1 Cohort 3: Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy elderly participants in double-blind, parallel group. |
| OG011 | Part 1 Cohort 3: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy elderly participants in double-blind, parallel group. |
| OG012 | Part 1 Cohort 4: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy adults in unblinded manner. |
| OG013 | Part 2 Cohort 5-7: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy in Cohort 5 to 7 under 2-period crossover design. |
| OG014 | Part 2 Cohort 5: TAK-925 44.8 mg | TAK-925 44.8 mg, infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy under 2-period crossover design. |
| OG015 | Part 2 Cohort 6: TAK-925 11.2 mg | TAK-925 11.2 mg, infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy under 2-period crossover design. |
| OG016 | Part 2 Cohort 7: TAK-925 5 mg | TAK-925 5 mg, infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy under 2-period crossover design. |
|
|
| Primary | Number of Participants Who Experience at Least One TEAE Related to Vital Signs | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
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|
| Primary | Number of Participants Who Experience at Least One TEAE Related to Body Weight | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
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|
|
| Primary | Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG) | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
|
|
| Primary | Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
|
|
| Primary | Part 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 M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or cerebrospinal fluid (CSF) concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
|
|
|
| Primary | Part 2, 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 M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
|
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|
| Primary | Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | ng/mL | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | ng/mL | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Geometric Mean | Standard Deviation | ng/mL | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Median | Full Range | hours | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Median | Full Range | hours | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Mean | Standard Deviation | hours | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Mean | Standard Deviation | hours | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | liter | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | liter | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | liter | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | liter | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, CL: Total Clearance After Intravenous Administration for TAK-925 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | liter per hour (L/h) | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion |
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| Primary | Part 2, CL: Total Clearance After Intravenous Administration for TAK-925 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | L/h | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion |
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| Primary | Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24 | Urine assessments were done only in Part 1, as planned. | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | microgram (mcg) | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion |
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| Primary | Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2 | Urine assessments were done only in Part 1, as planned. | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "overall participants analyzed" are participants who were available for this outcome measure assessment at given time period. | Posted | Mean | Standard Deviation | percentage of dose | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion |
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| Primary | Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2 | Urine assessments were done only in Part 1, as planned. | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. | Posted | Mean | Standard Deviation | L/h | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion |
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| Primary | Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4 | The PK analysis set was defined as all participants who received at least one dose of study drug and whose plasma or CSF concentration was measured at least once or whose cumulative urinary excretion was calculated. | Posted | Mean | Standard Deviation | Ratio | Day 1 at 6 hours after start of infusion |
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| Secondary | Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT) | 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 pharmacodynamic analysis set was defined as all participants who received at least one dose of study drug. | Posted | Mean | Standard Deviation | minutes | Days 1 and 3 up to 8 hours following the start of infusion |
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|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 1 |
| 11 |
| EG001 | Part 1 Cohort 1: TAK-925 7 mg | TAK-925 7 mg, infusion, intravenously, once on Day 1 in healthy adults in Group A to D in double-blind, alternating panel. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | Part 1 Cohort 2: TAK-925 14 mg | TAK-925 14 mg, infusion, intravenously, once on Day 1 in healthy adults in Group E to H in double-blind, alternating panel. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Part 1 Cohort 1: TAK-925 28 mg | TAK-925 28 mg, infusion, intravenously, once on Day 1 in healthy adults in Group A to D in double-blind, alternating panel. | 0 | 5 | 0 | 5 | 1 | 5 |
| EG004 | Par 1 Cohort 2: TAK-925 56 mg | TAK-925 56 mg, infusion, intravenously, once on Day 1 in healthy adults in Group E to H in double-blind, alternating panel. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | Part 1 Cohort 1: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy adults in Group A to D in double-blind, alternating panel. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG006 | Part 1 Cohort 2: TAK-925 134.4 mg | TAK-925 134.4 mg, infusion, intravenously, once on Day 1 in healthy adults in Group E to H in double-blind, alternating panel. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG007 | Part 1 Cohort S1-S2: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG008 | Part 1 Cohort S1: TAK-925 180 mg | TAK-925 180 mg, infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG009 | Part 1 Cohort S2: TAK-925 240 mg | TAK-925 240 mg, infusion, intravenously, once on Day 1 in healthy adults in double-blind, parallel group. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG010 | Part 1 Cohort 3: Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 in healthy elderly participants in double-blind, parallel group. | 0 | 2 | 0 | 2 | 0 | 2 |
| EG011 | Part 1 Cohort 3: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy elderly participants in double-blind, parallel group. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG012 | Part 1 Cohort 4: TAK-925 112 mg | TAK-925 112 mg, infusion, intravenously, once on Day 1 in healthy adults in unblinded manner. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG013 | Part 2 Cohort 5-7: Pooled Placebo | TAK-925 placebo-matching infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy in Cohort 5 to 7 under 2-period crossover design. | 0 | 13 | 0 | 13 | 0 | 13 |
| EG014 | Part 2 Cohort 5: TAK-925 44.8 mg | TAK-925 44.8 mg, infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy under 2-period crossover design. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG015 | Part 2 Cohort 6: TAK-925 11.2 mg | TAK-925 11.2 mg, infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy under 2-period crossover design. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG016 | Part 2 Cohort 7: TAK-925 5 mg | TAK-925 5 mg, infusion, intravenously, once on Day 1 or Day 3 in participants with type 1 narcolepsy under 2-period crossover design. | 0 | 6 | 0 | 6 | 0 | 6 |
| Feeling drunk | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Electrocardiogram PR prolongation | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Heart rate increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| White blood cell count increased | Investigations | 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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| Orthostatic hypotension | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Narcolepsy | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Euphoric mood | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
| Hypnagogic hallucination | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
| Logorrhoea | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
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.
| Male |
|
| Current smoker |
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| Former smoker |
|
| A Few Times Per Week |
|
| A Few Times Per Month |
|
| Non-alcoholic |
|
| Had no caffeine consumption |
|
|
| Metabolite M1 |
|
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| Metabolite M2 |
|
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| Metabolite M1 |
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| Metabolite M2 |
|
|
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| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
| Metabolite M1 |
|
|
| Metabolite M2 |
|
|
| Metabolite M1 |
|
| Metabolite M2 |
|
| Metabolite M1 |
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| Metabolite M2 |
|
|
| Metabolite M1 |
|
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| Metabolite M2 |
|
|
| Title | Measurements |
|---|---|
|
| <0.0001 |
The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group. |
| Superiority |
| ANOVA | 0.0001 | The p-value for each treatment group is for the comparison of that treatment group to the placebo treatment group. | Superiority |