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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- Eisai Inc.
- 入组人数
- 93
- 试验地点
- 1
- 主要终点
- Part B, AUC(0-t) of midazolam (MDZ)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body Mass Index (BMI) greater than or equal to (≥) 18 and less than (<) 30 kilograms per square meter (kg/m2) at Screening
- •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).
- •Non-smoking and non-vaping, healthy female, age ≥18 years and ≤55 years old at the time of informed consent (only Part C).
排除标准
- •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
- •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).
- •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
- •Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
- •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
- •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
- •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
- •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
- •Systolic blood pressure >140 millimeters of mercury (mmHg) or diastolic blood pressure >90 mmHg at Screening or Baseline
- •Heart rate <50 beats per (/) min or >100 beats/min at Screening or Baseline
- •Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the Columbia-Suicide Severity Rating Scale (C-SSRS).
- •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]).
- •Known history of clinically significant drug allergy at Screening
- •Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening
- •Known to be human immunodeficiency virus (HIV) positive at Screening
- •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.
- •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
- •Use of illegal recreational drugs and marijuana
- •Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week before dosing.
- •A history of noncompliance in any previous study or inability to comply with study conduct, as assessed by the investigator
- •Any other findings that the investigator feels would increase the risk of having an adverse outcome from participating in the study
- •Subjects carrying human leukocyte antigen (HLA)-B*1502 or HLA-A*3101 (only Part A -CBZ treatment group)
- •Genetically determined poor metabolizers of CYP2D6 substrates (only Part B - MDZ, DEX, and BUP)
研究组 & 干预措施
Part A: E2086 + Itraconazole
Oral doses of E2086 in healthy male and female participants dosed alone or in combination with itraconazole at steady state
干预措施: E2086 (Drug)
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
干预措施: E2086 (Drug)
Part A: E2086 + Carbamazepine
Oral doses of E2086 in healthy male and female participants dosed alone or in combination with carbamazepine at steady state
干预措施: E2086 (Drug)
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
干预措施: E2086 (Drug)
结局指标
主要结局
Part B, AUC(0-t) of midazolam (MDZ)
时间窗: Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-t) of dextromethorphan (DEX)
时间窗: Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-t) of bupropion (BUP)
时间窗: Day 4 to Day 8; Day 18 to Day 22
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
时间窗: 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
时间窗: Day 1 to Day 4; Day 7 to Day 13
Part A, maximum observed concentration (Cmax) of E2086 and its Metabolite M1
时间窗: Day 1; Day 7
Part B, AUC(0-t) of hydroxybupropion
时间窗: Day 4 to Day 8; Day 18 to Day 22
Part B, AUC(0-inf) of MDZ
时间窗: Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-inf) of DEX
时间窗: Day 1 to Day 4; Day 15 to Day 18
Part B, AUC(0-inf) of BUP
时间窗: Day 4 to Day 8; Day 18 to Day 22
Part B, AUC(0-inf) of hydroxybupropion
时间窗: Day 4 to Day 8; Day 18 to Day 22
Part B, Cmax of MDZ
时间窗: Day 1 and Day 15
Part B, Cmax of DEX
时间窗: Day 1 and Day 15
Part B, Cmax of BUP
时间窗: Day 4 and Day 18
Part B, Cmax of hydroxybupropion
时间窗: Day 4 and Day 18
Part C, AUC(0-t) of ethinyl estradiol (EE)
时间窗: Day 1 to Day 5; Day 12 to Day 16
Part C, AUC(0-t) of norethindrone (NET)
时间窗: Day 1 to Day 5; Day 12 to Day 16
Part C, AUC(0-inf) of EE
时间窗: Day 1 to Day 5; Day 12 to Day 16
Part C, AUC(0-inf) of NET
时间窗: Day 1 to Day 5; Day 12 to Day 16
Part C, Cmax of EE
时间窗: Day 1; Day 12
Part C, Cmax of NET
时间窗: Day 1 and Day 12
次要结局
- 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)