Narcolepsy
Conditions
Interventions
NT1Cohort
E2086:
Receive sequential dose escalation of E2086 tablets (low, middle, and high dose levels), administered orally, once daily, with each dose level administered for 4 weeks
Placebo:
Receiv
Sponsors
Tago Fumitoshi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, age greater than or equal to (>=) 18 years (or as regionally appropriate) at the time of informed consent 2. NT1 Cohort: Must fulfill Inclusion Criteria 2a and 2b a. Diagnosis of NT1 within the last 10 years of screening, as confirmed by at least one of the following: -Polysomnography (PSG) and Multiple Sleep Latency Test (MSLT) results, and clinical history, consistent with the 2023 International Classification of Sleep Disorders, 3rd edition, text revision (ICSD-3-TR) criteria for NT1 -Cerebrospinal fluid orexin-A/hypocretin-1 concentration less than or equal to (=10 5. Reports regular bedtime, defined as the time that the subject attempts to sleep, between 22:00 and 01:00 (based on data from the screening Diary) 6. Reports regular waketime, defined at the time the subject gets out of bed for the day, between 05:00 and 10:00 (based on data from the screening Diary) 7. Reports being in bed between 7 and 9 hours per night (based on data from the sleep portion of the Diary) 8. Compliance rate >= 80 percentage (%) for completion of the Diary during screening 9. Body mass index (BMI) >=18 to less than (<) 35 kilograms per square meter (kg/m^2) at Screening
Exclusion criteria
Exclusion criteria: 1. Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first 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: a. total abstinence b. an intrauterine device or intrauterine hormone-releasing system (IUS) c. a contraceptive implant d. Combined estrogen and progestogen-containing hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation, such as desogestrel (oral, injectable). Subjects using hormonal contraceptives must be on a stable dose of the same contraceptive product for at least 28 days before dosing, throughout the study and for at least 28 days following study drug discontinuation e. 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 28 days after study drug discontinuation. Subjects on an oral contraceptive must use an additional study method throughout the study and for 28 days after study drug discontinuation. For sites outside of Europe, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, ie, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. 3. Clinically significant illness that requires medical treatment within 8 weeks of dosing or a clinically significant infection that requires medical treatment within 4 weeks of dosing 4. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing 5. Any history of surgery that may affect PK profiles of E2086 or who have a congenital abnormality in metabolism at Screening 6 6. Any clinically abnormal symptom or organ impairment found by medical history at Screening, including severe renal impairment (estimated glomerular filtration rate [eGFR] 130 or 85 or <50 mmHg at Screening, or at Baseline. If outside of these limits at Screening or Baseline, BP should be repeated twice with at least 5 minutes between measurements 9. Persistent HR less than 50 beats/min or more than 100 beats/min at Screening, or at Baseline. If outside of these limits at Screening or Baseline, HR should be repeated twice with at least 5 minutes between measurements 10. Any lifetime history of suicidal behavior as indicated by the C-SSRS 11. Current unstable psychiatric disorder, current active major depressive episode or an active major depressive episode in the past 6 months 12. Any suicidal ideation with intent with or without a plan at
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline to Week 4 in MSL for E2086 Compared with Placebo Across Four MWTs in Participants with NT1 and NT2 | — |
Secondary
| Measure | Time frame |
|---|---|
| -Weekly Cataplexy Rate of E2086 Compared with Placebo at Week 4 in Participants With NT1 -Change From Baseline in the Epworth Sleepiness Scale (ESS) Total Score to Week 4 for E2086 Compared With Placebo in Participants With NT1 andNT2 -Number of Participants With Treatment-emergent Adverse Events(TEAEs) and Serious Adverse Events (SAEs) in Participants With NT1 and NT2 -Number of Participants With Markedly Abnormal Laboratory Values in Participants With NT1 and NT2 -Number of Participants With Clinically Significant Changes in Vital Sign Values in Participants With NT1 and NT2 -Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Parameters in Participants With NT1 and NT2 -Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) in Participants With NT1 and NT2 -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 -Mean Change From Baseline in Day time and Night-time BP Measured by ABPM in Participants With NT1 and NT2 | — |
Countries
Belgium, Canada, China, Germany, Italy, Japan, South Korea, Spain, Switzerland, United States
Contacts
Public ContactInquiry service
Eisai Co., Ltd.
Outcome results
None listed