A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of E2086 in Adults with Narcolepsy
A Study to Evaluate the Efficacy and Safety of E2086 in Adults With Narcolepsy
Tago Fumitoshi
Eisai Co., Ltd.
4-6-10 Koishikawa, Bunkyo-ku, Tokyo
+81-3-3817-5361
eisai-chiken_hotline@hhc.eisai.co.jp
Inquiry service
Eisai Co., Ltd.
4-6-10 Koishikawa, Bunkyo-ku, Tokyo
+81-3-3817-5361
eisai-chiken_hotline@hhc.eisai.co.jp
Recruiting
April. 30, 2026
April. 22, 2026
64
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
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 (<=) 110 picograms per milliliter (pg/mL)
b. At least 4 or more episodes of cataplexy/week as averaged over 2 weeks minimum and confirmed by the cataplexy portion of the Diary
If PSG or MSLT results are not available within the last 10 years of screening to fulfill Criterion 2a then screening assessment results for PSG or MSLT can be used instead.
3. NT2 Cohort: Diagnosis of NT2 within the last 10 years of screening, as confirmed by PSG and MSLT results, and clinical history, consistent with the 2023 ICSD-3-TR criteria for NT2.
If PSG or MSLT results are not available within the last 10 years of screening to fulfill Criterion 3 then screening assessment results for PSG or MSLT can be used instead.
4. ESS score >=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
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] <30 mL/min), and physical examinations, vital signs, ECG findings, or laboratory test results that require medical treatment at Screening or Baseline
7. A prolonged QTc interval calculated using Fridericia's formula (QTcF) greater than 450 ms according to central reading at Screening or Baseline. If the QTcF machine read is greater than 450 ms on the first single 12-lead ECG, 2 additional 12-lead ECGs will be performed 1 minute apart and the mean of the 3 QTcF values will be calculated
8. Persistent systolic BP >130 or <100 mmHg or diastolic BP >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 Screening or within 6 months of Screening
13. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics within 2 years before Screening
14. Hypersensitivity to the study drug or any of the excipients
15. Intake of herbal preparations containing St. John's Wort within 5 x the half-life before dosing
16. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the subject's ability to safely complete the study
17. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery which requires only local anesthesia and that can be undertaken as a day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the investigator this operation does not interfere with study procedures and subject safety
18. Known to be human immunodeficiency virus (HIV) positive
19. Acute Epstein Barr virus (EBV) infection with a positive EBV Viral Capsid Antigen Antibody (VCA) IgM at Baseline
20. Known to be hepatitis B virus (HBV)-positive with a detectable HBV (eg, hepatitis B surface antigen [HBsAg] reactive) within 6 months before the 1st dose of study drug, or hepatitis C virus (HCV)-positive with a detectable (eg, HCV RNA [qualitative]) viral load.
21. Initiation of statin therapy, or a change to a different statin, or an increase in the dose of a statin within the 6 months before the planned start of study drug
22. History of formally diagnosed moderate to severe obstructive sleep apnea (OSA)
23. Current use of continuous positive airway pressure (CPAP), hypoglossal nerve stimulator, oral device, or other therapy for the treatment of OSA
24. Symptomatic restless legs syndrome
25. Apnea-hypopnea index >=15 on Screening PSG
26. Use of anticataplectic medications (including but not limited to antidepressants) within 5 x the half-life before Screening
27. Use of psychostimulant medications, prescription and over-the-counter (OTC), within 5 x the half-life before Screening until after the Follow-Up Visit. Examples of prohibited medications include OTC stimulants
28. Use of sleep promoting or sedating medications, prescription and OTC, within 5 x the half-life before Screening until after the Follow-Up Visit.
29. Inability to discontinue use of strong (such as antifungal itraconazole and antibiotic clarithromycin) and moderate (such as antifungal fluconazole) Cytochrome P450 3A (CYP) 3A inhibitors within 5x the half-life before dosing until after the Follow-Up Visit
30. Inability to discontinue use of CYP3A inducers (such as antibiotic rifampicin and anti-convulsant phenytoin) within 5x the half-life before dosing until after the Follow-Up Visit
31. History of drug or alcohol dependency or abuse within 2 years before Screening, or those who have a positive urine drug test or breath (or urine) alcohol test at Screening or Baseline
32. Does not agree to abstain from use of recreational drugs during the study
33. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5 x the half-life, whichever is longer, preceding informed consent
34. Receipt of blood products within 4 weeks of dosing, donation of blood within 8 weeks of dosing, or donation of plasma within 1 week of dosing
35. Past participation in a study of an orexin agonist if discontinuation of orexin agonist use was related to an adverse drug reaction or inefficacy
18age old over
No limit
Both
Narcolepsy
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:
Receive one E2086-matched placebo tablet, orally, once daily administered for 12 weeks.
NT2 Cohort
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:
receive one E2086-matched placebo tablet, orally, once daily administered for 12 weeks.
Change from Baseline to Week 4 in MSL for E2086 Compared with Placebo Across Four MWTs in Participants with NT1 and NT2
-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
