Healthy Volunteers
Conditions
Brief summary
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
Interventions
DRUGE2086
Specified dose on specified days
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parts A, B, and C are a fixed-sequence crossover.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| 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
| 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 |
Countries
United States
Contacts
CONTACTEisai Medical Information
Outcome results
None listed