A Study to Evaluate the Efficacy, Safety, and Tolerability of E2086 Compared to Placebo and Active Comparator in Adult Participants With Narcolepsy Type 1

NCT06462404 | Completed Phase 1 FDA Drug

• 1 other identifier: E2086-A001-101
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 14

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).

Conditions

Narcolepsy Type 1 (NT1)

Keywords

Narcolepsy; E2086

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  At Day 17

Secondary Outcomes (15)

• MSL as Assessed by the 4 MWTs for E2086 Versus Active Comparator

  Days 1, 5, 9, 13 and 17

• Karolinska Sleepiness Scale (KSS) Score for E2086 Versus Active Comparator

  Day 1 up to Day 18

• KSS Score for E2086 Versus Placebo

  Day 1 up to Day 18

• 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

Study Arms (10)

Sequence 1, ABECD: Placebo + E2086 Dose 1 + Active Comparator + E2086 Dose 2 + E2086 Dose 3

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 2, BCADE: E2086 Dose 1 + E2086 Dose 2 + Placebo + E2086 Dose 3 + Active Comparator

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 3, CDBEA: E2086 Dose 2 + E2086 Dose 3 + E2086 Dose 1 + Active Comparator + Placebo

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 4, DECAB: E2086 Dose 3 + Active Comparator + E2086 Dose 2 + Placebo + E2086 Dose 1

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 5, EADBC: Active Comparator + Placebo + E2086 Dose 3 + E2086 Dose 1 + E2086 Dose 2

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 6, DCEBA: E2086 Dose 3 + E2086 Dose 2 + Active Comparator + E2086 Dose 1 + Placebo

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 7, EDACB: Active Comparator + E2086 Dose 3 + Placebo + E2086 Dose 2 + E2086 Dose 1

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 8, AEBDC: Placebo + Active Comparator + E2086 Dose 1 + E2086 Dose 3 + E2086 Dose 2

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 9, BACED: E2086 Dose 1 + Placebo + E2086 Dose 2 + Active Comparator + E2086 Dose 3

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Sequence 10, CBDAE: E2086 Dose 2 + E2086 Dose 1 + E2086 Dose 3 + Placebo + Active Comparator

EXPERIMENTAL

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Drug: E2086; Drug: E2086 Placebo; Drug: Active Comparator; Drug: Active Comparator Placebo

Interventions

E2086 DRUG

E2086 oral tablets.

Sequence 1, ABECD: Placebo + E2086 Dose 1 + Active Comparator + E2086 Dose 2 + E2086 Dose 3; Sequence 10, CBDAE: E2086 Dose 2 + E2086 Dose 1 + E2086 Dose 3 + Placebo + Active Comparator; Sequence 2, BCADE: E2086 Dose 1 + E2086 Dose 2 + Placebo + E2086 Dose 3 + Active Comparator; Sequence 3, CDBEA: E2086 Dose 2 + E2086 Dose 3 + E2086 Dose 1 + Active Comparator + Placebo; Sequence 4, DECAB: E2086 Dose 3 + Active Comparator + E2086 Dose 2 + Placebo + E2086 Dose 1; Sequence 5, EADBC: Active Comparator + Placebo + E2086 Dose 3 + E2086 Dose 1 + E2086 Dose 2; Sequence 6, DCEBA: E2086 Dose 3 + E2086 Dose 2 + Active Comparator + E2086 Dose 1 + Placebo; Sequence 7, EDACB: Active Comparator + E2086 Dose 3 + Placebo + E2086 Dose 2 + E2086 Dose 1; Sequence 8, AEBDC: Placebo + Active Comparator + E2086 Dose 1 + E2086 Dose 3 + E2086 Dose 2; Sequence 9, BACED: E2086 Dose 1 + Placebo + E2086 Dose 2 + Active Comparator + E2086 Dose 3

E2086 Placebo DRUG

E2086 matching placebo tablet.

Sequence 1, ABECD: Placebo + E2086 Dose 1 + Active Comparator + E2086 Dose 2 + E2086 Dose 3; Sequence 10, CBDAE: E2086 Dose 2 + E2086 Dose 1 + E2086 Dose 3 + Placebo + Active Comparator; Sequence 2, BCADE: E2086 Dose 1 + E2086 Dose 2 + Placebo + E2086 Dose 3 + Active Comparator; Sequence 3, CDBEA: E2086 Dose 2 + E2086 Dose 3 + E2086 Dose 1 + Active Comparator + Placebo; Sequence 4, DECAB: E2086 Dose 3 + Active Comparator + E2086 Dose 2 + Placebo + E2086 Dose 1; Sequence 5, EADBC: Active Comparator + Placebo + E2086 Dose 3 + E2086 Dose 1 + E2086 Dose 2; Sequence 6, DCEBA: E2086 Dose 3 + E2086 Dose 2 + Active Comparator + E2086 Dose 1 + Placebo; Sequence 7, EDACB: Active Comparator + E2086 Dose 3 + Placebo + E2086 Dose 2 + E2086 Dose 1; Sequence 8, AEBDC: Placebo + Active Comparator + E2086 Dose 1 + E2086 Dose 3 + E2086 Dose 2; Sequence 9, BACED: E2086 Dose 1 + Placebo + E2086 Dose 2 + Active Comparator + E2086 Dose 3

Active Comparator DRUG

Active comparator oral tablets.

Sequence 1, ABECD: Placebo + E2086 Dose 1 + Active Comparator + E2086 Dose 2 + E2086 Dose 3; Sequence 10, CBDAE: E2086 Dose 2 + E2086 Dose 1 + E2086 Dose 3 + Placebo + Active Comparator; Sequence 2, BCADE: E2086 Dose 1 + E2086 Dose 2 + Placebo + E2086 Dose 3 + Active Comparator; Sequence 3, CDBEA: E2086 Dose 2 + E2086 Dose 3 + E2086 Dose 1 + Active Comparator + Placebo; Sequence 4, DECAB: E2086 Dose 3 + Active Comparator + E2086 Dose 2 + Placebo + E2086 Dose 1; Sequence 5, EADBC: Active Comparator + Placebo + E2086 Dose 3 + E2086 Dose 1 + E2086 Dose 2; Sequence 6, DCEBA: E2086 Dose 3 + E2086 Dose 2 + Active Comparator + E2086 Dose 1 + Placebo; Sequence 7, EDACB: Active Comparator + E2086 Dose 3 + Placebo + E2086 Dose 2 + E2086 Dose 1; Sequence 8, AEBDC: Placebo + Active Comparator + E2086 Dose 1 + E2086 Dose 3 + E2086 Dose 2; Sequence 9, BACED: E2086 Dose 1 + Placebo + E2086 Dose 2 + Active Comparator + E2086 Dose 3

Active Comparator Placebo DRUG

Active comparator matching placebo tablet.

Sequence 1, ABECD: Placebo + E2086 Dose 1 + Active Comparator + E2086 Dose 2 + E2086 Dose 3; Sequence 10, CBDAE: E2086 Dose 2 + E2086 Dose 1 + E2086 Dose 3 + Placebo + Active Comparator; Sequence 2, BCADE: E2086 Dose 1 + E2086 Dose 2 + Placebo + E2086 Dose 3 + Active Comparator; Sequence 3, CDBEA: E2086 Dose 2 + E2086 Dose 3 + E2086 Dose 1 + Active Comparator + Placebo; Sequence 4, DECAB: E2086 Dose 3 + Active Comparator + E2086 Dose 2 + Placebo + E2086 Dose 1; Sequence 5, EADBC: Active Comparator + Placebo + E2086 Dose 3 + E2086 Dose 1 + E2086 Dose 2; Sequence 6, DCEBA: E2086 Dose 3 + E2086 Dose 2 + Active Comparator + E2086 Dose 1 + Placebo; Sequence 7, EDACB: Active Comparator + E2086 Dose 3 + Placebo + E2086 Dose 2 + E2086 Dose 1; Sequence 8, AEBDC: Placebo + Active Comparator + E2086 Dose 1 + E2086 Dose 3 + E2086 Dose 2; Sequence 9, BACED: E2086 Dose 1 + Placebo + E2086 Dose 2 + Active Comparator + E2086 Dose 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age greater than or equal to (\>=) 18 years at the time of informed consent
• 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
• Epworth Sleepiness Scale score \>=10
• 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)
• 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)
• Reports being in bed between 7 and 9 hours per night (based on data from the Screening Sleep/Cataplexy Diary)
• Body mass index (BMI) \>=18 to less than (\<) 40 kilograms per meter square (kg/m\^2), at Screening

You may not qualify if:

• 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
• 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).
• History of myocardial infarction, ischemic heart disease, or cardiac failure at Screening
• History of clinically significant arrhythmia or uncontrolled arrhythmia
• Known to have or probable positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 14 days of any study visit.
• Exposure within the last 10 days to an individual with confirmed or probable coronavirus disease-2019 (COVID-19) or symptoms within the last 10 days that are on the most recent Centers for Disease Control and Prevention (CDC) list of COVID symptoms

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (14)

SDS Clinical Trials

Santa Ana, California, 48911, United States

Location

PharmaDev Clinical Research

Miami, Florida, 33126, United States

Location

Sleep Practioners, LLC

Macon, Georgia, 31210, United States

Location

Clinical Research Institute

Stockbridge, Georgia, 30281, United States

Location

Sound Asleep Research, Inc.

Lansing, Michigan, 48911, United States

Location

Research Carolina Elite

Denver, North Carolina, 28037, United States

Location

Medical Care Inc.

Goldsboro, North Carolina, 27534, United States

Location

Advances Repiratory and Sleep Medicine

Greensboro, North Carolina, 27410, United States

Location

Intrepid Research, LLC

Cincinnati, Ohio, 45245, United States

Location

Bogan Sleep Consultants, LLC

Columbia, South Carolina, 29201, United States

Location

Sleep Therapy and Research Center

San Antonio, Texas, 78229, United States

Location

Comprehensive Sleep Medicine Associates

Sugar Land, Texas, 77478, United States

Location

AMDX Inc.

Markham, Ontario, L3R 1A3, Canada

Location

Jodha Tishon Inc

Toronto, Ontario, M5S 3A3, Canada

Location

MeSH Terms

Conditions

Narcolepsy

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2024
• First Posted: June 17, 2024
• Study Start: June 20, 2024
• Primary Completion: March 17, 2025
• Study Completion: March 17, 2025
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (12); CA (2)