A Trial to Evaluate the Efficacy and Safety of E2086 in Adults With Narcolepsy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eisai Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-07-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Eisai Ltd. European Knowledge Centre Mosquito Way Hatfield, Hertfordshire AL10 9SN UK

External identifiers

EU CT number

2025-523503-30-00

WHO UTN

U1111-1336-4340

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety

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]).

Secondary objectives 5

1. To identify the optimal doses of E2086 compared to placebo in subjects with narcolepsy Type 1 (NT1) for the reduction of weekly cataplexy rate (WCR).
2. To evaluate the efficacy of a range of doses of E2086 compared to placebo in subjects with narcolepsy for the reduction in EDS as assessed by the Epworth Sleepiness Scale (ESS).
3. To evaluate the safety and tolerability of a range of doses of E2086 in subjects with narcolepsy.
4. To evaluate the effect of E2086 compared with placebo on blood pressure (BP) assessed by ambulatory blood pressure monitoring (ABPM).
5. To evaluate the pharmacokinetics (PK) of E2086 and metabolite M1 in subjects with narcolepsy following multiple doses of E2086.

Conditions and MedDRA coding

Narcolepsy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Male or female, age ≥18 years (or as regionally appropriate) at the time of informed consent
2. 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. 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. 4. ESS score ≥10
5. 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. 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. 7. Reports being in bed between 7 and 9 hours per night (based on data from the sleep portion of the Diary)
8. 8. Compliance rate ≥80% for completion of the Diary during screening
9. 9. Body mass index (BMI) >=18 to less than (<) 35 kilograms per square meter (kg/mˆ2) at Screening

Exclusion criteria 35

1. 1. 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 IU/L or equivalent units of ß-hCG [or hCG]). 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. 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 (if it is their preferred and usual lifestyle) 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. 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 (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
3. 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. 4. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing (for example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system)
5. 5. Any history of surgery that may affect PK profiles of E2086 (for example, hepatectomy, nephrectomy, digestive organ resection) 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 milliliters per minute (mL/min), and physical examinations, vital signs, ECG findings, or laboratory test results that require medical treatment at Screening or Baseline
7. 7. A prolonged QTc interval calculated using Fridericia’s formula (QTcF) greater than 450 milliseconds (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. 8. Persistent systolic BP greater than (>) 130 or <100 millimeters of mercury (mmHg) or diastolic BP >85 or <50 mmHg at Screening (based on BP measured on at least 3 occasions over 2 weeks), 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. 9. Persistent HR less than 50 beats/min or more than 100 beats/min at Screening (based on HR measured on at least 3 occasions over 2 weeks), 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. 10. Any lifetime history of suicidal behavior as indicated by the C–SSRS
11. 11. Current unstable psychiatric disorder, current active major depressive episode or an active major depressive episode in the past 6 months
12. 12. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (that is, answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the C–SSRS)
13. 13. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics within 2 years before Screening
14. 14. Hypersensitivity to the study drug or any of the excipients
15. 15. Intake of herbal preparations containing St. John’s Wort within 5x the half-life before dosing
16. 16. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant’s ability to safely complete the study
17. 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 participant safety
18. 18. Known to be human immunodeficiency virus (HIV) positive
19. 19. Acute Epstein Barr virus (EBV) infection with a positive EBV Viral Capsid Antigen Antibody (VCA) IgM at Baseline
20. 20. Known to be hepatitis B virus (HBV)-positive with a detectable HBV (for example, 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 (for example, HCV ribonucleic acid (RNA) [qualitative]) viral load. Note: Participants who are HCV positive due to prior resolved disease can be enrolled, only if a confirmatory negative HCV RNA test is obtained and the participant has completed active treatment
21. 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. 22. History of formally diagnosed moderate to severe obstructive sleep apnea (OSA)
23. 23. Current use of continuous positive airway pressure (CPAP), hypoglossal nerve stimulator, oral device, or other therapy for the treatment of OSA
24. 24. Symptomatic restless legs syndrome
25. 25. Apnea-hypopnea index >=15 on Screening PSG
26. 26. Use of anticataplectic medications (including but not limited to antidepressants) within 5× the half-life before Screening
27. 27. Use of psychostimulant medications, prescription and over-the-counter (OTC), within 5× the half-life before Screening until after the Follow-Up Visit. Examples of prohibited medications include OTC stimulants (for example, pseudoephedrine), methylphenidate, amphetamines, modafinil, armodafinil, sodium oxybate, pitolisant, solriamfetol, and pemoline
28. 28. Use of sleep promoting or sedating medications, prescription and OTC, within 5x the half-life before Screening until after the Follow-Up Visit. Examples of prohibited medication include OTC sleep aids, trazodone, hypnotics, benzodiazepines, barbiturates, cannabinoids, melatonin, melatonin receptor agonists, dual orexin receptor antagonists, and opioids
29. 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. 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. 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. 32. Does not agree to abstain from use of recreational drugs during the study
33. 33. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5x the half-life, whichever is longer, preceding informed consent
34. 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. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline to Week 4 in MSL for E2086 Compared With Placebo Across Four MWTs in Participants With NT1 and NT2

Secondary endpoints 14

1. Weekly Cataplexy Rate (WCR) of E2086 Compared With Placebo at Week 4 in Participants With NT1
2. 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
3. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Participants With NT1 and NT2
4. Number of Participants With Markedly Abnormal Laboratory Values in Participants With NT1 and NT2
5. Number of Participants With Clinically Significant Changes in Vital Sign Values in Participants With NT1 and NT2
6. Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Parameters in Participants With NT1 and NT2
7. Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) in Participants With NT1 and NT2
8. 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
9. Mean Change From Baseline in Day-time and Night-time BP Measured by ABPM in Participants With NT1 and NT2
10. Cmax: Maximum Observed Plasma Concentration of E2086 and its Metabolite M1
11. Tmax: Time to Reach Cmax of E2086 and its Metabolite M1
12. AUC(0-24h): Area Under the Plasma Concentration–time Curve From Zero Time to 24 Hours of E2086 and its Metabolite M1
13. t½: Terminal Phase Half-life of E2086 and its Metabolite M1
14. MRp: Metabolite Ratio of AUC(0-t)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eisai Limited

Sponsor organisation

Eisai Limited

Address

European Knowledge Center, Mosquito Way Mosquito Way

City

Hatfield

Postcode

AL10 9SN

Country

United Kingdom

Scientific contact point

Organisation

Eisai Limited

Contact name

Medical Information

Public contact point

Organisation

Eisai Limited

Contact name

Medical Information

Third parties 9

Locations

3 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications