Idiopathic Hypersomnia
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the safety and tolerability of administering a single intravenous (IV) infusion dose of TAK-925 to adult participants with idiopathic hypersomnia (IH).
Detailed description
The drug being tested in this study in participants with IH is called TAK-925. The study will have 2-treatment crossover groups. The study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single intravenous (IV) dose of Dose A in participants with IH. The study will enroll 40 patients. Participants will be randomly assigned to one of the two treatment sequence groups as indicated below: * TAK-925 + Placebo * Placebo + TAK-925 On Day 1 of each treatment period, TAK-925 or placebo will be administered as a single 9-hour IV infusion. The multicenter study will be conducted in the United States and Japan. The overall duration of treatment in this study is approximately 41 days including screening up to 28 days, confinement for 6 days and end of study follow up telephone call on Study Day 11.
Interventions
DRUGTAK-925
TAK-925 IV infusion.
DRUGTAK-925 Placebo
TAK-925 placebo-matching IV infusion.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. A diagnosis of IH, as defined by the International Classification of Sleep Disorders-3 (ICSD-3) as verified by a previous nocturnal polysomnography (nPSG) and multiple sleep latency test (MSLT) study performed within the last 10 years. 2. Onset of hypersomnia between 10 and 30 years of age. 3. Seven consecutive days of actigraphy supported by a sleep diary obtained prior to the nPSG (Study Day -2) shows an average nightly sleep duration of greater than or equal to (\>=) 420 minutes during the participant's normal nocturnal sleep period. 4. nPSG (Study Day -2) demonstrates that participant does not have other comorbid sleep disorders or clinically significant nocturnal hypoxemia (oxygen saturation ≤80% for ≥5% of total sleep time) and that their Apnea-Hypopnea Index (AHI) is less than or equal to (\<=) 10 per hour, their periodic limb movement arousal index (PLMAI) \<=15/hour, and that their total sleep time is \>=6.5 hours. 5. Participants taking medication for treatment of excessive daytime sleepiness (EDS) must be willing to discontinue medication prior to randomization into the study. 6. Body mass index (BMI) of 18 through 33 kilogram per square meter (kg/m\^2) inclusive. 7. Epworth Sleepiness Scale (ESS) score \>=11 at screening and on Day -2. 8. Blood pressure (BP) must be \<140 mmHg (systolic) and \<90 mmHg (diastolic) at screening and Study Day -2.
Exclusion criteria
1. Average nightly sleep duration is \<=8 hours (480 minutes) and has insufficient sleep syndrome as evidenced by sleeping \>2 hours/night more on off-days relative to work days as determined by actigraphy and sleep diary obtained prior to the nPSG (Study Day -2). 2. Positive urine screen for drugs of abuse and/or positive alcohol test at screening and Study Day -2. 3. Resting heart rate (HR) outside of the range of 40 to 90 beats pper minute (bpm) off stimulants. 4. Screening electrocardiogram (ECG) reveals a QT interval with Fridericia correction method \>450 ms (men) or \>470 ms (women). 5. Usual bedtime later than 24:00 (midnight) or an occupation requiring nighttime shift work or variable shift work within the past 6 months, or travel with significant jet lag within 14 days before Study Day -2. 6. History of a sleep disorder other than IH, based on interviews at the screening visit, such as obstructive sleep apnea (OSA), restless legs syndrome, or periodic limb movements of sleep (PLMS) associated with arousals. 7. Use of any over-the-counter (OTC) or prescription medications with stimulating properties within 7 days prior to dosing or 5 half-lives (whichever is longer) that could affect the evaluation of EDS or use of sodium oxybate within 3 months of screening. 8. Nicotine dependence that is likely to have an effect on sleep (e.g., a participant who routinely awakens at night to smoke) and/or an unwillingness to discontinue all smoking and nicotine use during the confinement portion of the study (Day -2 to Day 4). 9. Caffeine consumption of more than 600 mg/day for 7 days before Study Day 1 (1 serving of coffee is approximately equivalent to 120 mg of caffeine) and/or unwilling to discontinue all caffeine during the confinement portion of the study (Day -2 to Day 4). 10. Alcohol use that is likely to have an effect on sleep and/or an unwillingness to discontinue all alcohol use from 72 hours before check-in through discharge on Study Day 4. 11. History of epilepsy or seizures, including having had a single seizure or a history of childhood febrile seizures or has a clinically significant history of head trauma. 12. Answered YES on Questions 4 or 5 on the Suicidal Ideation subscale of the Columbia Suicide Severity Rating Scale (C-SSRS) at screening (defined period as 3 months prior to screening) or evidence of suicidal behavior within 6 months of screening as measured by the Suicidal Behavior subscale of the C-SSRS. 13. Diagnosis of major depressive disorder (DSM-5), within the past 6 months or Beck Depression Inventory II (BDI-II) total score of \>16 at the screening visit. 14. History of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation. 15. Known coronary artery disease, a history of myocardial infarction, angina, cardiac rhythm abnormality, or heart failure.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | Study Day 1 up to Study Day 11 |
| Percentage of Participants With Markedly Abnormal Criteria for Clinical Safety Laboratory Tests | Study Day 1 up to Study Day 11 |
| Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | From Predose up to Study Day 4 |
| Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | Study Day 1 up to Study Day 4 |
Secondary
| Measure | Time frame |
|---|---|
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 | Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion |
| AUC Last: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-925 | Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion |
| Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion |
Countries
Japan, United States
Participant flow
Recruitment details
Participants took part in the study at 13 investigative sites in the United States and Japan from 26 January 2020 to 23 November 2020.
Pre-assignment details
Participants with idiopathic hypersomnia (IH) were enrolled in one of the two treatment sequences of this 2-period crossover study to receive TAK-925 112 milligram (mg) infusion or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: TAK 925 112 mg + Placebo TAK-925 112 mg, infusion, intravenously, once on Day 1 (Study Day 1) of Treatment Period 1, followed by 24 hours washout period, further followed by placebo, infusion, intravenously, once on Day 1 (Study Day 3) of Treatment Period 2. | 13 |
| Sequence 2: Placebo + TAK-925 112 mg Placebo, infusion, intravenously, once on Day 1 (Study Day 1) of Treatment Period 1, followed by 24 hours washout period, further followed by TAK-925 112 mg, intravenously, once on Day 1 (Study Day 3) of Treatment Period 2. | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (1 Day) | Other | 1 | 0 |
| Washout Period (1 Day) | Other | 0 | 1 |
| Washout Period (1 Day) | Protocol deviation | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence 1: TAK 925 112 mg + Placebo | Total | Sequence 2: Placebo + TAK-925 112 mg |
|---|---|---|---|
| Age, Continuous | 32.0 years STANDARD_DEVIATION 9.97 | 31.7 years STANDARD_DEVIATION 8.79 | 31.5 years STANDARD_DEVIATION 7.91 |
| Body Mass Index (BMI) | 23.47 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.336 | 25.31 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.857 | 27.02 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.597 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 25 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 165.18 centimeter (cm) STANDARD_DEVIATION 8.077 | 167.73 centimeter (cm) STANDARD_DEVIATION 9.253 | 170.10 centimeter (cm) STANDARD_DEVIATION 9.924 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 18 Participants | 10 Participants |
| Region of Enrollment Japan | 3 Participants | 4 Participants | 1 Participants |
| Region of Enrollment United States of America | 10 Participants | 23 Participants | 13 Participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
| Weight | 64.33 kilogram (kg) STANDARD_DEVIATION 11.501 | 71.87 kilogram (kg) STANDARD_DEVIATION 15.652 | 78.88 kilogram (kg) STANDARD_DEVIATION 16.067 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 25 |
| other Total, other adverse events | 2 / 27 | 5 / 25 |
| serious Total, serious adverse events | 0 / 27 | 0 / 25 |
Outcome results
Primary
Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: Study Day 1 up to Study Day 11
Population: The safety analysis set included all participants who were randomized and received at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 14.8 percentage of participants |
| TAK-925 112 mg | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 40.0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters
Time frame: Study Day 1 up to Study Day 4
Population: The safety analysis set included all participants who were randomized and received at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | PR Interval, Aggregate: >=200 msec | 3.7 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QTcF Interval, Aggregate: >500 msec | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QRS Duration, Aggregate: >=180 msec | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QTcF Interval, Aggregate: >=30 change from baseline and >450 msec | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QRS Duration, Aggregate: <= 80 msec | 11.1 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | Heart Rate: <40 bpm | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QTcF Interval, Aggregate: <=300 msec | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | Heart Rate: >115 bpm | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | PR Interval, Aggregate: <=80 millisecond (msec) | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | Heart Rate: >115 bpm | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | PR Interval, Aggregate: <=80 millisecond (msec) | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | PR Interval, Aggregate: >=200 msec | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QRS Duration, Aggregate: <= 80 msec | 12.0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QRS Duration, Aggregate: >=180 msec | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QTcF Interval, Aggregate: <=300 msec | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QTcF Interval, Aggregate: >500 msec | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | QTcF Interval, Aggregate: >=30 change from baseline and >450 msec | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-lead Safety Electrocardiogram (ECG) Parameters | Heart Rate: <40 bpm | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Criteria for Clinical Safety Laboratory Tests
Time frame: Study Day 1 up to Study Day 11
Population: The safety analysis set included all participants who were randomized and received at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Clinical Safety Laboratory Tests | 3.7 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Clinical Safety Laboratory Tests | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements
Time frame: From Predose up to Study Day 4
Population: The safety analysis set included all participants who were randomized and received at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Systolic Blood Pressure: less than (<) 90 millimeter of mercury (mmHg) | 14.8 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Systolic Blood Pressure: greater than or equal to (>=) 160mmHg | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Systolic Blood Pressure: Change from predose greater than (>) 20 mmHg | 11.1 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Diastolic Blood Pressure: <50 mmHg | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Diastolic Blood Pressure: >=100 mmHg | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Diastolic Blood Pressure: Change from predose >20 mmHg | 14.8 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Heart Rate: <40 beats per minute (bpm) | 0 percentage of participants |
| Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Heart Rate: >115 bpm | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Heart Rate: >115 bpm | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Systolic Blood Pressure: less than (<) 90 millimeter of mercury (mmHg) | 12.0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Diastolic Blood Pressure: >=100 mmHg | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Systolic Blood Pressure: greater than or equal to (>=) 160mmHg | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Heart Rate: <40 beats per minute (bpm) | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Systolic Blood Pressure: Change from predose greater than (>) 20 mmHg | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Diastolic Blood Pressure: Change from predose >20 mmHg | 0 percentage of participants |
| TAK-925 112 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements | Diastolic Blood Pressure: <50 mmHg | 4.0 percentage of participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925
Time frame: Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion
Population: The PK analysis set included participants who receive at least 1 dose of study drug and who had at least 1 measurable plasma concentration of TAK-925 (or its metabolites). Here overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 | 2253 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 22.5 |
Secondary
AUC Last: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-925
Time frame: Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion
Population: The PK analysis set included participants who receive at least 1 dose of study drug and who had at least 1 measurable plasma concentration of TAK-925 (or its metabolites). Here overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC Last: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-925 | 2265 ng*h/mL | Geometric Coefficient of Variation 22.3 |
Secondary
Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925
Time frame: Treatment Periods 1 and 2: Study Day 1 pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion
Population: The Pharmacokinetic (PK) analysis set included participants who receive at least 1 dose of study drug and who had at least 1 measurable plasma concentration of TAK-925 (or its metabolites). Here overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925 | 222.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31.3 |