Narcolepsy Type 1 (NT1)
Conditions
Keywords
Narcolepsy, E2086
Brief summary
The primary purpose of this study is to evaluate the efficacy of single oral doses of E2086 compared to placebo in the treatment of excessive daytime sleepiness (EDS) as assessed by the Maintenance of Wakefulness Test (MWT) in adult participants with narcolepsy type 1 (NT1).
Interventions
DRUGE2086
E2086 oral tablets.
DRUGE2086 Placebo
E2086 matching placebo tablet.
DRUGActive Comparator
Active comparator oral tablets.
DRUGActive Comparator Placebo
Active comparator matching placebo tablet.
Sponsors
Eisai 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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, age greater than or equal to (\>=) 18 years at the time of informed consent 2. Diagnosis of NT1 defined by the following criteria: * History of daily periods of the irrepressible need to sleep, or daytime lapses into sleep, occurring for at least 3 months * History of cataplexy (which must be confirmed during the Screening Period by Sleep/Cataplexy Diary) * At least one of the following: * On Screening multiple sleep latency test (MSLT): MSL of less than or equal to (\<=) 8 minutes and 2 or more sleep onset rapid eye movement periods (SOREMPs) on an MSLT performed according to standard techniques * On Screening nocturnal polysomnography (PSG): One or more SOREMPs within 15 minutes of sleep onset 3. Epworth Sleepiness Scale score \>=10 4. Reports regular bedtime, defined as the time that the participant attempts to sleep, between 22:00 and midnight (based on data from the Screening Sleep/Cataplexy Diary) 5. Reports regular waketime, defined at the time the participant gets out of bed for the day, between 05:00 and 10:00 (based on data from the Screening Sleep/Cataplexy Diary) 6. Reports being in bed between 7 and 9 hours per night (based on data from the Screening Sleep/Cataplexy Diary) 7. Body mass index (BMI) \>=18 to less than (\<) 40 kilograms per meter square (kg/m\^2), at Screening
Exclusion criteria
1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[ß-hCG\] or human chorionic gonadotropin \[hCG\] test with a minimum sensitivity of 25 international units per liter (IU/L) or equivalent units of ß-hCG \[or hCG\]), and females who are breastfeeding or pregnant during the Treatment Period. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the 1st dose of study drug 2. Females of childbearing potential who: * Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: * total abstinence (if it is their preferred and usual lifestyle) * a nonhormonal intrauterine device (example, coil) or a progesterone-only intrauterine hormone-releasing system * a nonsteroidal oral contraceptive (participant must have been on a stable dose of the same nonsteroidal oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 28 days after study drug discontinuation.) * depot medroxyprogesterone acetate or depot norethisterone enantate. * have a vasectomized partner with confirmed azoospermia. * Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 30 days after study drug administration. * Participants on an oral contraceptive must use an additional barrier method throughout the study and for 30 days after study drug administration. NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that are, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). 3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Sleep Latency (MSL) as Assessed by the 4 Maintenance of Wakefulness Tests (MWTs) for E2086 Versus Placebo at Day 1 | At Day 1 | Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective assessment of excessive daytime sleepiness (EDS) which consists of measurement tests. A participant undergoes four 40-minute wake trials, where an increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. These measurements of sleep latency at regular intervals across the day are averaged to calculate the mean sleep latency. The MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine. |
| MSL as Assessed by the 4 MWTs for E2086 Versus Placebo at Day 5 | At Day 5 | Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective assessment of EDS which consists of measurement tests. A participant undergoes four 40-minute wake trials, where an increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. These measurements of sleep latency at regular intervals across the day are averaged to calculate the mean sleep latency. The MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine. |
| MSL as Assessed by the 4 MWTs for E2086 Versus Placebo at Day 9 | At Day 9 | Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective assessment of EDS which consists of measurement tests. A participant undergoes four 40-minute wake trials, where an increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. These measurements of sleep latency at regular intervals across the day are averaged to calculate the mean sleep latency. The MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine. |
| MSL as Assessed by the 4 MWTs for E2086 Versus Placebo at Day 13 | At Day 13 | Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective assessment of EDS which consists of measurement tests. A participant undergoes four 40-minute wake trials, where an increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. These measurements of sleep latency at regular intervals across the day are averaged to calculate the mean sleep latency. The MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine. |
| MSL as Assessed by the 4 MWTs for E2086 Versus Placebo at Day 17 | At Day 17 | Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective assessment of EDS which consists of measurement tests. A participant undergoes four 40-minute wake trials, where an increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. These measurements of sleep latency at regular intervals across the day are averaged to calculate the mean sleep latency. The MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Markedly Abnormal Vital Sign Values | Baseline up to Day 20 | Vital sign parameters will include systolic and diastolic blood pressure, pulse, respiratory rate, body temperature. |
| Number of Participants With Markedly Abnormal Electrocardiogram (ECGs) Findings | Baseline up to Day 20 | — |
| Number of Participants With Markedly Abnormal Electroencephalogram (EEGs) Findings | Baseline up to Day 20 | — |
| Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | Baseline up to Day 20 | Suicidality will be assessed using the C-SSRS. The C-SSRS assesses an individual's degree of suicidality, including suicidal ideation and suicidal behavior. The C-SSRS is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior is indicated when response is yes for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation is indicated when response is yes for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide. |
| Cmax: Maximum Observed Plasma Concentration of E2086 and its Metabolite M1 | Days 1, 5, 9, 13 and 17: 0-24 hours post-dose | — |
| MSL as Assessed by the 4 MWTs for E2086 Versus Active Comparator | Days 1, 5, 9, 13 and 17 | Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective assessment of EDS which consists of measurement tests. A participant undergoes four 40-minute wake trials, where an increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. These measurements of sleep latency at regular intervals across the day are averaged to calculate the mean sleep latency. The MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine. |
| AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration of E2086 and its Metabolite M1 | Days 1, 5, 9, 13 and 17: 0-24 hours post-dose | — |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Zero Time Extrapolated to Infinite of E2086 and its Metabolite M1 | Days 1, 5, 9, 13 and 17: 0-24 hours post-dose | — |
| t½: Terminal Phase Half-life of E2086 and its Metabolite M1 | Days 1, 5, 9, 13 and 17: 0-24 hours post-dose | — |
| MRp: Metabolite Ratio of AUC(0-inf) | Days 1, 5, 9, 13 and 17: 0-24 hours post-dose | MRp will be calculated as ratio of plasma AUC(0-inf) of metabolite to parent following molar correction. |
| Tmax: Time to Reach Cmax of E2086 and its Metabolite M1 | Days 1, 5, 9, 13 and 17: 0-24 hours post-dose | — |
| Karolinska Sleepiness Scale (KSS) Score for E2086 Versus Active Comparator | Day 1 up to Day 18 | The KSS is a subjective measure of an individual's level of sleepiness during the last 10 minutes, as assessed at a particular time of day. The KSS is rated on a 10-point scale, from 1 = extremely alert, to 10 = extremely sleepy, falls asleep all the time. Higher score indicates more sleepiness. |
| KSS Score for E2086 Versus Placebo | Day 1 up to Day 18 | The KSS is a subjective measure of an individual's level of sleepiness during the last 10 minutes, as assessed at a particular time of day. The KSS is rated on a 10-point scale, from 1 = extremely alert, to 10 = extremely sleepy, falls asleep all the time. Higher score indicates more sleepiness. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From first dose of study drug up to Day 20 | — |
| Number of Participants With Markedly Abnormal Clinical Laboratory Values | Baseline up to Day 20 | Clinical laboratory will include hematology, chemistry, and urinalysis. |
Countries
Canada, United States
Outcome results
None listed