The primary purpose of this study is to evaluate the optimal doses of E2086 compared to placebo in participants with narcolepsy for reduction of excessive daytime sleepiness (EDS) as assessed by Mean Sleep Latency (MSL) (measured from the first 4 maintenance of wakefulness tests \[MWTs\]).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
64
Change from Baseline to Week 4 in MSL for E2086 Compared With Placebo Across Four MWTs in Participants With NT1 and NT2
Sleep latency is defined as the amount of time a person takes to fall asleep. The MWT is an objective measure of the ability to stay awake. An increased ability to stay awake in the context of trying to remain awake is reflected in a prolonged sleep latency. The first 4 measurements of sleep latency at regular intervals across the day are averaged to calculate the MSL. The MWT is used to evaluate response to treatment for conditions associated with EDS and to assess alertness in individuals who must remain awake for safety reasons. The 40-minute MWT will be performed as per the 2021 guidance of the American Academy of Sleep Medicine (AASM).
Time frame: Baseline and Week 4
Weekly Cataplexy Rate (WCR) of E2086 Compared With Placebo at Week 4 in Participants With NT1
WCR assess through participant-reported daily diaries, is a standard measure of cataplexy burden in clinical development programs for narcolepsy treatments, similar in importance to the MWT used for evaluating EDS.
Time frame: At Week 4
Change From Baseline in the Epworth Sleepiness Scale (ESS) Total Score to Week 4 for E2086 Compared With Placebo in Participants With NT1 and NT2
The ESS is a subjective measure of daytime sleepiness. The participant rates on a 4-point Likert scale how likely it is that he/she would doze in 8 different situations. Scoring of the answers is 0 to 3, with 0 being "would never doze" and 3 being "high chance of dozing". The total ESS score ranges from 0 to 24, with higher scores indicating greater daytime sleepiness. Scores above 10 are considered indicative of EDS. A decrease from baseline in ESS score represents improvement.
Time frame: Baseline and Week 4
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Participants With NT1 and NT2
Time frame: From first dose of study drug up to Day 113
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Number of Participants With Markedly Abnormal Laboratory Values in Participants With NT1 and NT2
Laboratory parameters will include hematology, chemistry and urinalysis.
Time frame: Up to Day 113
Number of Participants With Clinically Significant Changes in Vital Sign Values in Participants With NT1 and NT2
Vital signs will include measurement of systolic and diastolic blood pressure (BP), heart rate, respiratory rate and body temperature. Any clinically significant change in vital signs will be determined at the investigator's discretion.
Time frame: Up to Day 113
Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Parameters in Participants With NT1 and NT2
The 12-lead ECG will be evaluated. Any clinically significant change in ECG assessment will be determined at the investigator's discretion.
Time frame: Up to Day 113
Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) in Participants With NT1 and NT2
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 behaviour, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behaviour. Any suicidal behaviour is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behaviour, 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: Up to Day 113
Mean Change From Baseline in 24-hours Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) up to Week 4 of each dose level in Participants With NT1 and NT2
The BP will be evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the measurement of BP recordings after every 24 hours.
Time frame: Baseline and Week 4
Mean Change From Baseline in Day-time and Night-time BP Measured by ABPM in Participants With NT1 and NT2
The BP will be evaluated by ABPM for all participants based on the measurement of BP recordings after every 24 hours.
Time frame: Baseline and Week 4
Cmax: Maximum Observed Plasma Concentration of E2086 and its Metabolite M1
Time frame: Days 28, 63 and 98: 0-24 hours post-dose
Tmax: Time to Reach Cmax of E2086 and its Metabolite M1
Time frame: Days 28, 63 and 98: 0-24 hours post-dose
AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours of E2086 and its Metabolite M1
Time frame: Days 28, 63 and 98: 0-24 hours post-dose
t½: Terminal Phase Half-life of E2086 and its Metabolite M1
Time frame: Days 28, 63 and 98: 0-24 hours post-dose
MRp: Metabolite Ratio of AUC(0-t)
MRp calculated as ratio of plasma AUC(0-t) of metabolite to parent following molar correction where appropriate. AUC(0-t) is 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 28, 63 and 98: 0-24 hours post-dose