Healthy Participants, Narcolepsy
Conditions
Brief summary
The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925 when administered to healthy participants and narcolepsy participants.
Detailed description
The drug being tested in this study is called TAK-925. TAK-925 is being tested in healthy participants and participants with narcolepsy. This study will look at the safety, tolerability, pharmacokinetics, and efficacy of TAK-925. This study will consist of three parts. Part A will be a randomized, double-blind, placebo-controlled, multiple rising dose (MRD) study in healthy participants. Part B is a randomized, double-blind, placebo-controlled MRD study in participants with narcolepsy. Part C is a randomized, double-blind, placebo-controlled, parallel group, multiple repeat dose study in participants with narcolepsy. Part A' is a single dose study in healthy participants. The study will enroll approximately 96 participants planned as total. All participants except Part A' will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need): Part A: * TAK-925 (Dose Levels A1-A6) * Placebo Part B: * TAK-925 (Dose Levels B1-B4) * Placebo Part C: * TAK-925 (Dose Levels C1-C2) * Placebo Part A': • TAK-925 (Dose Levels A'1-A'2) All participants will be asked to take TAK-925 or Placebo at the same time each day from Day 1 to Day 7 in Parts A, B and C, and take TAK-925 on Day 1 in Part A'. This multi-center trial will be conducted in Japan. The overall study period is approximately 15 days in Parts A, B and C, and approximately 7 days for Part A'. Participants will be partly admitted to a hospital during the study.
Interventions
DRUGTAK-925
TAK-925
DRUGPlacebo
TAK-925 Placebo
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy adult participants and Healthy elderly participants: • Participant weighs at least 50 kg (Healthy adults participants) / 40 kilogram (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 participants: * Participants weighs at least 40 kg inclusive at Screening (\>=50 kg is required for Cohort B4). * A diagnosis of narcolepsy, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3). * At Day -1, Epworth sleepiness scale (ESS) score \>=10
Exclusion criteria
All Participants: * Participants consume excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. * Participants have a moderate to severe substance use disorder. * Participants have a risk of suicide according to endorsement of item 4 or 5 with Screening/Baseline visit C-SSRS (Columbia Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months. * Participants have a lifetime history of major psychiatric disorder, such as bipolar disorder or schizophrenia. * Participants experienced sleep wake cycle disturbance with external factors such as irregular work hours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf | This assessment was pre-specified to be conducted for participants in Part A', Cohort A'1: TAK-925 112 mg as exploratory measures. |
| Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf | This assessment was pre-specified to be conducted for participants in Part A', Cohort A'1: TAK-925 112 mg as exploratory measures. |
| Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf | Accumulation Ratio of AUC was calculated as AUCtau on Day 7 divided by AUCtau on Day 1. This assessment was pre-specified to be conducted for participants in Part A', Cohort A'1: TAK-925 112 mg as exploratory measures. |
| Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline, Day 1 and Day 7 | The MWT is a validated objective measure that is used to measure excessive daytime sleepiness in clinical studies. It has been used as a secondary outcome measure for excessive daytime sleepiness. The MWT evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Wakefulness in this study was measured indirectly by time to fall asleep using MWT. In this study, four 40-minute (1 session) MWT assessments per day was administered on Baseline, Day 1 and Day 7. MWT sleep latency ranges from 0 to 40 minutes, with longer sleep latency indicating greater ability to stay awake. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 3 investigative sites in Japan from 21 November 2018 to 24 October 2019.
Pre-assignment details
Healthy participants were enrolled in Part A and A' (exploratory), NT1 in Part B and NT2 in Part C, to receive TAK-925 multiple rising dose of 44 mg (milligram), 112 mg,180 mg or placebo in Part A, 11 mg, 44 mg or placebo in Part B, multiple dose of TAK-925 44 mg, 112 mg or placebo in Part C.
Participants by arm
| Arm | Count |
|---|---|
| Part A, Cohorts A1-A3: Pooled Placebo TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants. | 6 |
| Part A, Cohort A1: TAK-925 44 mg TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants. | 6 |
| Part A, Cohort A2: TAK-925 112 mg TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants. | 6 |
| Part A, Cohort A3: TAK-925 180 mg TAK-925 180 mg, infusion, intravenously, once daily from Day 1 through Day 7 in healthy participants. | 6 |
| Part B, Cohorts B1-B2: Pooled Placebo TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants. | 4 |
| Part B, Cohort B1: TAK-925 11 mg TAK-925 11 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants. | 4 |
| Part B, Cohort B2: TAK-925 44 mg TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT1 participants. | 5 |
| Part C, Cohorts C1-C2: Pooled Placebo TAK-925 placebo-matching, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants. | 5 |
| Part C, Cohort C1: TAK-925 44 mg TAK-925 44 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants. | 4 |
| Part C, Cohort C2: TAK-925 112 mg TAK-925 112 mg, infusion, intravenously, once daily from Day 1 through Day 7 in NT2 participants. | 5 |
| Part A', Cohort A'1: TAK-925 112 mg TAK-925 112 mg, solution, orally, once on Day 1 in healthy participants. | 6 |
| Total | 57 |
Baseline characteristics
| Characteristic | Total | Part A, Cohort A2: TAK-925 112 mg | Part A, Cohort A3: TAK-925 180 mg | Part B, Cohorts B1-B2: Pooled Placebo | Part B, Cohort B1: TAK-925 11 mg | Part A, Cohorts A1-A3: Pooled Placebo | Part B, Cohort B2: TAK-925 44 mg | Part A, Cohort A1: TAK-925 44 mg | Part C, Cohorts C1-C2: Pooled Placebo | Part C, Cohort C1: TAK-925 44 mg | Part C, Cohort C2: TAK-925 112 mg | Part A', Cohort A'1: TAK-925 112 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 26.6 years STANDARD_DEVIATION 7.04 | 23.8 years STANDARD_DEVIATION 3.54 | 22.3 years STANDARD_DEVIATION 0.52 | 28.3 years STANDARD_DEVIATION 9.18 | 38.0 years STANDARD_DEVIATION 3.92 | 24.8 years STANDARD_DEVIATION 4.71 | 27.6 years STANDARD_DEVIATION 8.2 | 24.7 years STANDARD_DEVIATION 3.88 | 31.8 years STANDARD_DEVIATION 11.14 | 31.3 years STANDARD_DEVIATION 7.5 | 25.0 years STANDARD_DEVIATION 5.87 | 21.7 years STANDARD_DEVIATION 2.88 |
| Body Mass Index (BMI) | 22.66 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 3.21 | 22.37 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.96 | 21.87 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.36 | 24.83 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 2.378 | 27.33 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 4.955 | 22.42 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 0.968 | 24.68 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 4.791 | 21.12 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.03 | 20.88 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 3.565 | 22.83 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 4.213 | 22.18 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 3.489 | 21.05 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.174 |
| Height | 167.8 centimeter (cm) STANDARD_DEVIATION 6.63 | 168.8 centimeter (cm) STANDARD_DEVIATION 5.85 | 170.8 centimeter (cm) STANDARD_DEVIATION 4.71 | 169.8 centimeter (cm) STANDARD_DEVIATION 7.8 | 165.3 centimeter (cm) STANDARD_DEVIATION 8.18 | 170.2 centimeter (cm) STANDARD_DEVIATION 4.71 | 166.8 centimeter (cm) STANDARD_DEVIATION 7.56 | 173.3 centimeter (cm) STANDARD_DEVIATION 4.84 | 162.2 centimeter (cm) STANDARD_DEVIATION 5.02 | 158.0 centimeter (cm) STANDARD_DEVIATION 5.6 | 164.6 centimeter (cm) STANDARD_DEVIATION 5.46 | 170.7 centimeter (cm) STANDARD_DEVIATION 3.44 |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — | — | — | — | — | — | — | — | — |
| Region of Enrollment Japan | 57 Participants | 6 Participants | 6 Participants | 4 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 4 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 13 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 44 Participants | 6 Participants | 6 Participants | 3 Participants | 2 Participants | 6 Participants | 3 Participants | 6 Participants | 2 Participants | 1 Participants | 3 Participants | 6 Participants |
| Weight | 64.14 kilogram (kg) STANDARD_DEVIATION 10.706 | 63.72 kilogram (kg) STANDARD_DEVIATION 7.392 | 63.60 kilogram (kg) STANDARD_DEVIATION 7.987 | 72.90 kilogram (kg) STANDARD_DEVIATION 13.071 | 75.20 kilogram (kg) STANDARD_DEVIATION 18.15 | 64.58 kilogram (kg) STANDARD_DEVIATION 5.486 | 70.32 kilogram (kg) STANDARD_DEVIATION 15.554 | 62.75 kilogram (kg) STANDARD_DEVIATION 3.25 | 56.20 kilogram (kg) STANDARD_DEVIATION 11.689 | 57.73 kilogram (kg) STANDARD_DEVIATION 13.072 | 61.68 kilogram (kg) STANDARD_DEVIATION 10.055 | 60.60 kilogram (kg) STANDARD_DEVIATION 4.549 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 2 / 6 | 4 / 6 | 1 / 4 | 1 / 4 | 5 / 5 | 0 / 5 | 1 / 4 | 3 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug.
Time frame: From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)
Population: The safety set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohorts A1-A3: Pooled Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Part A, Cohort A1: TAK-925 44 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Part A, Cohort A2: TAK-925 112 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Part A, Cohort A3: TAK-925 180 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part B, Cohorts B1-B2: Pooled Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Part B, Cohort B1: TAK-925 11 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Part B, Cohort B2: TAK-925 44 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Part C, Cohorts C1-C2: Pooled Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Part C, Cohort C1: TAK-925 44 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Part C, Cohort C2: TAK-925 112 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Part A', Cohort A'1: TAK-925 112 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
Secondary
Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925
This assessment was pre-specified to be conducted for participants in Part A', Cohort A'1: TAK-925 112 mg as exploratory measures.
Time frame: Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf
Population: The PK set was defined as all participants who received at least one dose of study drug and provided sufficient PK measurements available to estimate PK parameters, at least 1 estimable PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohorts A1-A3: Pooled Placebo | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 662.4 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 70.718 |
| Part A, Cohorts A1-A3: Pooled Placebo | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 650.7 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 78.156 |
| Part A, Cohort A1: TAK-925 44 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 1516 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 151.45 |
| Part A, Cohort A1: TAK-925 44 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 1523 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 174.4 |
| Part A, Cohort A2: TAK-925 112 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 2615 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 392.89 |
| Part A, Cohort A2: TAK-925 112 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 2747 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 372.96 |
| Part A, Cohort A3: TAK-925 180 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 164.2 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 18.257 |
| Part A, Cohort A3: TAK-925 180 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 182.7 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 22.603 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 682.3 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 126.81 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 722.7 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 102.28 |
| Part B, Cohort B1: TAK-925 11 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 648.3 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 80.748 |
| Part B, Cohort B1: TAK-925 11 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 657.1 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 72.833 |
| Part B, Cohort B2: TAK-925 44 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 1 | 1496 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 279.16 |
| Part B, Cohort B2: TAK-925 44 mg | Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925 | Day 7 | 1519 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 248.46 |
Secondary
Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925
This assessment was pre-specified to be conducted for participants in Part A', Cohort A'1: TAK-925 112 mg as exploratory measures.
Time frame: Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf
Population: The pharmacokinetic (PK) set was defined as all participants who received at least one dose of study drug and provided sufficient PK measurements available to estimate PK parameters, at least 1 estimable PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohorts A1-A3: Pooled Placebo | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 74.49 nanogram per milliliter (ng/mL) | Standard Deviation 4.3433 |
| Part A, Cohorts A1-A3: Pooled Placebo | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 70.31 nanogram per milliliter (ng/mL) | Standard Deviation 8.4434 |
| Part A, Cohort A1: TAK-925 44 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 166.9 nanogram per milliliter (ng/mL) | Standard Deviation 20.995 |
| Part A, Cohort A1: TAK-925 44 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 159.2 nanogram per milliliter (ng/mL) | Standard Deviation 23.56 |
| Part A, Cohort A2: TAK-925 112 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 300.2 nanogram per milliliter (ng/mL) | Standard Deviation 50.532 |
| Part A, Cohort A2: TAK-925 112 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 295.5 nanogram per milliliter (ng/mL) | Standard Deviation 46.173 |
| Part A, Cohort A3: TAK-925 180 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 17.39 nanogram per milliliter (ng/mL) | Standard Deviation 1.2842 |
| Part A, Cohort A3: TAK-925 180 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 17.68 nanogram per milliliter (ng/mL) | Standard Deviation 1.7176 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 70.20 nanogram per milliliter (ng/mL) | Standard Deviation 18.798 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 73.20 nanogram per milliliter (ng/mL) | Standard Deviation 14.98 |
| Part B, Cohort B1: TAK-925 11 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 68.74 nanogram per milliliter (ng/mL) | Standard Deviation 7.3623 |
| Part B, Cohort B1: TAK-925 11 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 70.87 nanogram per milliliter (ng/mL) | Standard Deviation 7.4375 |
| Part B, Cohort B2: TAK-925 44 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 1 | 156.1 nanogram per milliliter (ng/mL) | Standard Deviation 29.21 |
| Part B, Cohort B2: TAK-925 44 mg | Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Day 7 | 153.9 nanogram per milliliter (ng/mL) | Standard Deviation 24.876 |
Secondary
Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925
Accumulation Ratio of AUC was calculated as AUCtau on Day 7 divided by AUCtau on Day 1. This assessment was pre-specified to be conducted for participants in Part A', Cohort A'1: TAK-925 112 mg as exploratory measures.
Time frame: Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf
Population: The PK set was defined as all participants who received at least one dose of study drug and provided sufficient PK measurements available to estimate PK parameters, at least 1 estimable PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A, Cohorts A1-A3: Pooled Placebo | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 0.9832 ratio | Standard Deviation 0.041034 |
| Part A, Cohort A1: TAK-925 44 mg | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 1.009 ratio | Standard Deviation 0.080171 |
| Part A, Cohort A2: TAK-925 112 mg | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 1.050 ratio | Standard Deviation 0.02 |
| Part A, Cohort A3: TAK-925 180 mg | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 1.118 ratio | Standard Deviation 0.14637 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 1.062 ratio | Standard Deviation 0.066062 |
| Part B, Cohort B1: TAK-925 11 mg | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 1.017 ratio | Standard Deviation 0.098127 |
| Part B, Cohort B2: TAK-925 44 mg | Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925 | 1.018 ratio | Standard Deviation 0.03076 |
Secondary
Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7
The MWT is a validated objective measure that is used to measure excessive daytime sleepiness in clinical studies. It has been used as a secondary outcome measure for excessive daytime sleepiness. The MWT evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Wakefulness in this study was measured indirectly by time to fall asleep using MWT. In this study, four 40-minute (1 session) MWT assessments per day was administered on Baseline, Day 1 and Day 7. MWT sleep latency ranges from 0 to 40 minutes, with longer sleep latency indicating greater ability to stay awake.
Time frame: Baseline, Day 1 and Day 7
Population: The pharmacodynamic (PD) set was defined as all participants who received at least one dose of study drug. Here number analyzed n are the participants who were evaluable for the outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohorts A1-A3: Pooled Placebo | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 1 | -0.66 minutes | Standard Deviation 0.892 |
| Part A, Cohorts A1-A3: Pooled Placebo | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline | 1.97 minutes | Standard Deviation 0.85 |
| Part A, Cohorts A1-A3: Pooled Placebo | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 7 | -0.38 minutes | Standard Deviation 0.621 |
| Part A, Cohort A1: TAK-925 44 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 1 | 35.13 minutes | Standard Deviation 4.268 |
| Part A, Cohort A1: TAK-925 44 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline | 2.03 minutes | Standard Deviation 0.717 |
| Part A, Cohort A1: TAK-925 44 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 7 | 21.00 minutes | Standard Deviation 12.141 |
| Part A, Cohort A2: TAK-925 112 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 1 | 34.19 minutes | Standard Deviation 4.398 |
| Part A, Cohort A2: TAK-925 112 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline | 5.23 minutes | Standard Deviation 4.029 |
| Part A, Cohort A2: TAK-925 112 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 7 | 34.78 minutes | Standard Deviation 4.029 |
| Part A, Cohort A3: TAK-925 180 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 1 | 2.58 minutes | Standard Deviation 3.751 |
| Part A, Cohort A3: TAK-925 180 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline | 4.13 minutes | Standard Deviation 3.28 |
| Part A, Cohort A3: TAK-925 180 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 7 | 2.35 minutes | Standard Deviation 3.369 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 1 | 23.88 minutes | Standard Deviation 2.955 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline | 6.83 minutes | Standard Deviation 3.924 |
| Part B, Cohorts B1-B2: Pooled Placebo | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 7 | 25.79 minutes | Standard Deviation 7.544 |
| Part B, Cohort B1: TAK-925 11 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Baseline | 7.33 minutes | Standard Deviation 5.932 |
| Part B, Cohort B1: TAK-925 11 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 7 | 28.28 minutes | Standard Deviation 4.886 |
| Part B, Cohort B1: TAK-925 11 mg | Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7 | Change at Day 1 | 31.15 minutes | Standard Deviation 5.507 |
p-value: <0.0001Mixed Model for Repeated Measures (MMRM)
p-value: <0.0001MMRM
p-value: 0.0002MMRM
p-value: <0.0001MMRM
p-value: <0.0001MMRM
p-value: <0.0001MMRM
p-value: <0.0001MMRM
p-value: <0.0001MMRM