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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
22
E2086 oral tablets.
E2086 matching placebo tablet.
Active comparator oral tablets.
SDS Clinical Trials
Santa Ana, California, United States
PharmaDev Clinical Research
Miami, Florida, United States
Sleep Practioners, LLC
Macon, Georgia, United States
Mean Sleep Latency (MSL) as Assessed by the 4 Maintenance of Wakefulness Tests (MWTs) for E2086 Versus Placebo 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.
Time frame: At Day 1
MSL as Assessed by the 4 MWTs for E2086 Versus Placebo 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.
Time frame: At Day 5
MSL as Assessed by the 4 MWTs for E2086 Versus Placebo 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.
Time frame: At Day 9
MSL as Assessed by the 4 MWTs for E2086 Versus Placebo 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.
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Active comparator matching placebo tablet.
Clinical Research Institute
Stockbridge, Georgia, United States
Sound Asleep Research, Inc.
Lansing, Michigan, United States
Research Carolina Elite
Denver, North Carolina, United States
Medical Care Inc.
Goldsboro, North Carolina, United States
Advances Repiratory and Sleep Medicine
Greensboro, North Carolina, United States
Intrepid Research, LLC
Cincinnati, Ohio, United States
Bogan Sleep Consultants, LLC
Columbia, South Carolina, United States
...and 4 more locations
Time frame: At Day 13
MSL as Assessed by the 4 MWTs for E2086 Versus Placebo 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.
Time frame: At Day 17
MSL as Assessed by the 4 MWTs for E2086 Versus Active Comparator
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.
Time frame: Days 1, 5, 9, 13 and 17
Karolinska Sleepiness Scale (KSS) Score for E2086 Versus Active Comparator
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.
Time frame: Day 1 up to Day 18
KSS Score for E2086 Versus Placebo
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.
Time frame: Day 1 up to Day 18
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug up to Day 20
Number of Participants With Markedly Abnormal Clinical Laboratory Values
Clinical laboratory will include hematology, chemistry, and urinalysis.
Time frame: Baseline up to Day 20
Number of Participants With Markedly Abnormal Vital Sign Values
Vital sign parameters will include systolic and diastolic blood pressure, pulse, respiratory rate, body temperature.
Time frame: Baseline up to Day 20
Number of Participants With Markedly Abnormal Electrocardiogram (ECGs) Findings
Time frame: Baseline up to Day 20
Number of Participants With Markedly Abnormal Electroencephalogram (EEGs) Findings
Time frame: Baseline up to Day 20
Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
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.
Time frame: Baseline up to Day 20
Cmax: Maximum Observed Plasma Concentration of E2086 and its Metabolite M1
Time frame: Days 1, 5, 9, 13 and 17: 0-24 hours post-dose
Tmax: Time to Reach Cmax of E2086 and its Metabolite M1
Time frame: Days 1, 5, 9, 13 and 17: 0-24 hours post-dose
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
Time frame: 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
Time frame: Days 1, 5, 9, 13 and 17: 0-24 hours post-dose
t½: Terminal Phase Half-life of E2086 and its Metabolite M1
Time frame: Days 1, 5, 9, 13 and 17: 0-24 hours post-dose
MRp: Metabolite Ratio of AUC(0-inf)
MRp will be calculated as ratio of plasma AUC(0-inf) of metabolite to parent following molar correction.
Time frame: Days 1, 5, 9, 13 and 17: 0-24 hours post-dose