A Study to Assess Potential Drug-Drug Interactions of E2086 in Healthy Participants

A Phase 1, Open-label, 3-Part Study to Assess Potential Drug-Drug Interactions of E2086 When Coadministered Orally With Itraconazole, Carbamazepine, Midazolam, Dextromethorphan, Bupropion, or Combined Oral Contraceptives in Healthy Subjects

The primary purpose of this study is to assess potential drug-drug interactions of E2086 when coadministered orally with Itraconazole, Carbamazepine, Midazolam, Dextromethorphan, Bupropion, or Combined Oral Contraceptives in Healthy Participants

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: E2086

• Study Type: Interventional
• Enrollment (Estimated): 93
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Eisai Medical Information; Phone Number: +1-888-274-2378; Email: esi_medinfo@eisai.com

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Austin Clinical Research Unit (CRU)- Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Body Mass Index (BMI) greater than or equal to (≥) 18 and less than (<) 30 kilograms per square meter (kg/m2) at Screening
2. Non-smoking and non-vaping, healthy male or female, age ≥18 years and ≤55 years old at the time of informed consent (only Parts A and B).
3. Non-smoking and non-vaping, healthy female, age ≥18 years and ≤55 years old at the time of informed consent (only Part C).

Exclusion Criteria:

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 international units per liter (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. Females of childbearing potential who did not use a highly effective method of contraception (as described below) within 28 days before study entry, or who do not agree to use an approved method of contraception from 28 days before study entry throughout the entire study period, and for 28 days after study drug discontinuation.

   Approved (highly effective) methods of contraception for this study include at least 1 of the following:

   • Total abstinence (if it is her preferred and usual lifestyle)
   • Have a vasectomized partner with confirmed azoospermia
   • Double-barrier method (such as condom plus diaphragm with spermicide) NOTE: All females will be considered 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. Subjects who are using steroidal hormones including for contraceptives, implants and intrauterine system, or for any other indications from 4 weeks before informed consent until study discharge from the final period
4. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
5. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing; eg, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system
6. Any history of surgery that may affect pharmacokinetics (PK) profiles of E2086 (eg, hepatectomy, nephrectomy, digestive organ resection) or subjects who have a congenital abnormality in metabolism at Screening
7. Any clinically abnormal symptom or organ impairment found by medical history at Screening, including estimated glomerular filtration rate (eGFR) <90 milliliters per minute (ml/min), and physical examinations, vital signs, ECG findings, or laboratory test results that require medical treatment at Screening or Baseline
8. A prolonged QT/corrected (QTc) interval (QT interval corrected for heart rate using Fridericia's formula [QTcF] >450 millisecond [ms]) as demonstrated by the mean of triplicate ECGs (recorded at least 1 minute [min] apart) at Screening or Baseline
9. Systolic blood pressure >140 millimeters of mercury (mmHg) or diastolic blood pressure >90 mmHg at Screening or Baseline
10. Heart rate <50 beats per (/) min or >100 beats/min at Screening or Baseline
11. Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the Columbia-Suicide Severity Rating Scale (C-SSRS).
12. Any lifetime history of psychiatric disease (including, but not limited to, depression or other mood disorders, bipolar disorder, psychotic disorders, including schizophrenia, panic attacks, and anxiety disorders [if ever treated with medication]).
13. Known history of clinically significant drug allergy at Screening
14. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening
15. Known to be human immunodeficiency virus (HIV) positive at Screening
16. History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug test or breath alcohol test at Screening or Baseline.
17. Currently enrolled in another clinical study or used any investigational drug or device within 28 days (or 5 half-lives, whichever is longer) preceding informed consent
18. Use of illegal recreational drugs and marijuana
19. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week before dosing.
20. A history of noncompliance in any previous study or inability to comply with study conduct, as assessed by the investigator
21. Any other findings that the investigator feels would increase the risk of having an adverse outcome from participating in the study
22. Subjects carrying human leukocyte antigen (HLA)-B*1502 or HLA-A*3101 (only Part A -CBZ treatment group)
23. Genetically determined poor metabolizers of CYP2D6 substrates (only Part B - MDZ, DEX, and BUP)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: E2086 + Itraconazole; Oral doses of E2086 in healthy male and female participants dosed alone or in combination with itraconazole at steady state	Drug: E2086; Specified dose on specified days
Experimental: Part A: E2086 + Carbamazepine; Oral doses of E2086 in healthy male and female participants dosed alone or in combination with carbamazepine at steady state	Drug: E2086; Specified dose on specified days
Experimental: Part B: E2086 + Midazolam + Dextromethorphan + Bupropion; Oral doses of midazolam, dextromethorphan, and bupropion in healthy male and female participants dosed alone or in combination with E2086 at steady state	Drug: E2086; Specified dose on specified days
Experimental: Part C: E2086 + Ethinyl estradiol + Norethindrone; Single dose combined oral contraceptive (ethinyl estradiol and norethindrone) healthy female participants dosed alone or in combination with E2086 at steady state	Drug: E2086; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A, area under concentration versus time curve from zero time (predose) to time of last quantifiable concentration AUC(0-t) of E2086 and its Metabolite M1	Day 1 to Day 4; Day 7 to Day 13
Part A, area under concentration versus time curve from zero time (predose) to infinite time AUC(0-inf) of E2086 and its Metabolite M1	Day 1 to Day 4; Day 7 to Day 13
Part A, maximum observed concentration (Cmax) of E2086 and its Metabolite M1	Day 1; Day 7
Part B, AUC(0-t) of midazolam (MDZ)	Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-t) of dextromethorphan (DEX)	Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-t) of bupropion (BUP)	Day 4 to Day 8; Day 18 to Day 22
Part B, AUC(0-t) of hydroxybupropion	Day 4 to Day 8; Day 18 to Day 22
Part B, AUC(0-inf) of MDZ	Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-inf) of DEX	Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-inf) of BUP	Day 4 to Day 8; Day 18 to Day 22
Part B, AUC(0-inf) of hydroxybupropion	Day 4 to Day 8; Day 18 to Day 22
Part B, Cmax of MDZ	Day 1 and Day 15
Part B, Cmax of DEX	Day 1 and Day 15
Part B, Cmax of BUP	Day 4 and Day 18
Part B, Cmax of hydroxybupropion	Day 4 and Day 18
Part C, AUC(0-t) of ethinyl estradiol (EE)	Day 1 to Day 5; Day 12 to Day 16
Part C, AUC(0-t) of norethindrone (NET)	Day 1 to Day 5; Day 12 to Day 16
Part C, AUC(0-inf) of EE	Day 1 to Day 5; Day 12 to Day 16
Part C, AUC(0-inf) of NET	Day 1 to Day 5; Day 12 to Day 16
Part C, Cmax of EE	Day 1; Day 12
Part C, Cmax of NET	Day 1 and Day 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A, Number of Participants With Treatment-emergent Adverse Events (TEAEs) for single or multiple doses of E2086, ITZ, and CBZ	ITZ: Baseline up to Day 13; CBZ: Baseline up to Day 18
Part A, Number of Participants With Abnormal Laboratory Parameter Values for single or multiple doses of E2086, ITZ, and CBZ	ITZ: Baseline up to Day 13; CBZ: Baseline up to Day 18
Part A, Number of Participants With Clinically Significant Change in Vital Sign Values for single or multiple doses of E2086, ITZ, and CBZ	ITZ: Baseline up to Day 13; CBZ: Baseline up to Day 18
Part A, Number of Participants With Clinically Significant Change in 12-Lead Electrocardiogram (ECG) Values for single or multiple doses of E2086, ITZ, and CBZ	ITZ: Baseline up to Day 13; CBZ: Baseline up to Day 18
Part B, Number of Participants With TEAEs for single or multiple doses of E2086, MDZ, DEX, or BUP	Baseline up to Day 24
Part B, Number of Participants With Abnormal Laboratory Parameter Values for single or multiple doses of E2086, MDZ, DEX, or BUP	Baseline up to Day 24
Part B, Number of Participants With Clinically Significant Change in Vital Sign Values for single or multiple doses of E2086, MDZ, DEX, or BUP	Baseline up to Day 24
Part B, Number of Participants With Clinically Significant Change in 12-Lead ECG Values for single or multiple doses of E2086, MDZ, DEX, or BUP	Baseline up to Day 24
Part C, Number of Participants With TEAEs for coadministration of E2086 and combined oral contraceptive (COC)	Baseline up to Day 18
Part C, Number of Participants With Abnormal Laboratory Parameter Values for coadministration of E2086 and COC	Baseline up to Day 18
Part C, Number of Participants With Clinically Significant Change in Vital Sign Values for coadministration of E2086 and COC	Baseline up to Day 18
Part C, Number of Participants With Clinically Significant Change in 12-Lead ECG Values for coadministration of E2086 and COC	Baseline up to Day 18

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): August 12, 2026
• Primary Completion (Estimated): November 12, 2026
• Study Completion (Estimated): November 12, 2026

Study Registration Dates

• First Submitted: August 11, 2026
• First Submitted That Met QC Criteria: August 11, 2026
• First Posted (Actual): August 14, 2026

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: E2086-A001-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No