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A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants

2021年8月20日 更新者:Eisai Inc.

A Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose and Single Dose Food Effect Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730 in Healthy Subjects

The primary purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of E2730 of multiple ascending oral doses in healthy adult participants and to assess the differences in PK, safety, and tolerability of E2730 between healthy Japanese and non-Japanese participants following multiple doses. This study will also determine the effect of food on PK of E2730.

研究概览

研究类型

介入性

注册 (实际的)

32

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • California
      • Long Beach、California、美国、90806
        • Collaborative Neuroscience Research, LLC.

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 55年 (成人)

接受健康志愿者

是的

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Non-smoking, healthy male or female, age greater than or equal to (>=) 18 years and <55 years old at the time of informed consent. To be considered non-smokers, Participants must have discontinued smoking for at least 4 weeks before dosing
  2. Japanese Participants must have been born in Japan of Japanese parents and Japanese grandparents, must have lived no more than 5 years outside of Japan, and must not have changed their life style or habits, including diet, while living outside of Japan
  3. Body mass index (BMI) >=18 and <30 kilograms per meter square (kg/m^2) at Screening

Exclusion Criteria:

  1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] test). 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:
    • Total abstinence (if it is their preferred and usual lifestyle)
    • An intrauterine device or intrauterine hormone-releasing system (IUS)
    • A contraceptive implant
    • An oral contraceptive (Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 28 days after study drug discontinuation)
    • Have a vasectomized partner with confirmed azoospermia
    • Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation
  3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation)
  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; example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
  6. Any history of gastrointestinal surgery that may affect PK profiles of E2730, example, hepatectomy, nephrectomy, and digestive organ resection
  7. Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening
  8. A prolonged QT interval of the ECG/Corrected QT interval (QT/QTc) (QTcF greater than [>] 450 milliseconds [ms]) demonstrated by a repeated ECG at Screening or Baseline (based on average of triplicate ECGs). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval
  9. Persistent systolic BP >139 or <90 millimeter of mercury (mmHg) or diastolic BP >89 or <50 mmHg at Screening or Baseline
  10. Heart rate <45 beats/minute or >100 beats/minute 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) or equivalent scale or via interview with a psychiatrist
  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, anxiety disorders ). The absence of a history of psychiatric disease should be documented by a checklist in the electronic case report form (eCRF)
  13. Any current psychiatric symptoms as indicated by a standard screening tool
  14. 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)
  15. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS)
  16. Known history of clinically significant drug allergy at Screening
  17. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening
  18. Known to be human immunodeficiency virus (HIV) positive at Screening
  19. Active viral hepatitis (A, B, or C) and syphilis as demonstrated by positive serology at Screening
  20. History of drug or alcohol dependency or abuse, or those who have a positive drug test at Screening or Baseline
  21. Exposure within the last 14 days to an individual with confirmed or probable corona virus disease 2019 (COVID-19) or symptoms within the last 14 days that are on the most recent Centers for Disease Control and Prevention (CDC) list of COVID symptoms or any other reason to consider the participants at potential risk for an acute COVID-19 infection
  22. 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
  23. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing
  24. Any personal or family history of seizures (including febrile seizures) or epilepsy or episode of unexplained loss of consciousness
  25. Any history of neurological or other medical conditions which in the opinion of the investigator has the potential to reduce seizure threshold (example, history of head concussion, traumatic brain injury, alcohol abuse, substance abuse, developmental abnormalities in the brain)
  26. Any epileptiform discharges on resting EEG (including during hyperventilation and photo-stimulation)

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:其他
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:三倍

武器和干预

参与者组/臂
干预/治疗
实验性的:Part A, Cohort 1: E2730 20 Milligram (mg) or Placebo
Healthy Japanese and non-Japanese participants will receive E2730 20 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.
E2730 capsules.
E2730-matched placebo capsules.
实验性的:Part A, Cohort 2: E2730 40 mg or Placebo
Healthy Japanese and non-Japanese participants will receive E2730 40 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.
E2730 capsules.
E2730-matched placebo capsules.
实验性的:Part A, Cohort 3: E2730 60 mg or Placebo
Healthy Japanese and non-Japanese participants will receive E2730 60 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.
E2730 capsules.
E2730-matched placebo capsules.
实验性的:Part A, Cohort 4: E2730 80 mg or Placebo
Healthy Japanese and non-Japanese participants will receive E2730 80 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.
E2730 capsules.
E2730-matched placebo capsules.
实验性的:Part B, E2730 80 mg: Fasted + Fed
Participants will receive a single treatment of E2730 (80 mg capsule) in fasted condition on Day 1 treatment period 1 followed by E2730 80 mg capsule in fed condition on Day 1 of treatment period 2. A washout period of at least 21 days will be maintained between the 2 treatments.
E2730 capsules.
实验性的:Part B, E2730 80 mg: Fed + Fasted
Participants will receive a single treatment of E2730 80 mg capsule in fed condition on Day 1 of treatment period 1 followed by E2730 80 mg capsule in fasted condition on Day 1 of treatment period 2. A washout period of at least 21 days will be maintained between the 2 treatments.
E2730 capsules.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
大体时间:Screening up to Day 32 (approximately 60 days)
Safety assessments will consist of monitoring and recording all adverse events (AEs); laboratory evaluation for hematology, clinical chemistry, and urinalysis; periodic measurement of vital signs, electrocardiograms (ECGs), electroencephalogram (EEGs), corrected QT (QTc) interval and blood pressure.
Screening up to Day 32 (approximately 60 days)
Part A, Cmax: Maximum Observed Plasma Concentration for E2730
大体时间:Day 1: 0-24 hours; Day 18: 0-336 hours
Day 1: 0-24 hours; Day 18: 0-336 hours
Part A, Css,min: Minimum Observed Plasma Concentration at Steady State for E2730
大体时间:Time Frame: Day 18: 0-24 hours
Time Frame: Day 18: 0-24 hours
Part A, tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E2730
大体时间:Day 1: 0-24 hours; Day 18: 0-336 hours
Day 1: 0-24 hours; Day 18: 0-336 hours
Part A, Css,av: Average Steady State Plasma Concentration at Steady State for E2730
大体时间:Time Frame: Day 18: 0-24 hours
Time Frame: Day 18: 0-24 hours
Part A, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours After Dosing for E2730
大体时间:Day 1: 0-24 hours; Day 18: 0-24 hours
Day 1: 0-24 hours; Day 18: 0-24 hours
Part A, t1/2: Terminal Elimination Phase Half-life Following Last day of Dosing for E2730
大体时间:Day 18: 0-336 hours
Day 18: 0-336 hours
Part A, PTF: Peak-trough Fluctuation for E2730
大体时间:Day 18: 0-24 hours
Day 18: 0-24 hours
Part A, Rac: Accumulation Ratio for Cmax and AUC for E2730
大体时间:Day 1: 0-24 hours; Day 18: 0-24 hours
Day 1: 0-24 hours; Day 18: 0-24 hours
Part A, CLss/F: Apparent Total Clearance Following Extravascular Administration at Steady State for E2730
大体时间:Day 18: 0-336 hours
Day 18: 0-336 hours
Part A, Vz/F: Apparent Volume of Distribution at Terminal Phase
大体时间:Day 18: 0-336 hours
Day 18: 0-336 hours
Part B, Cmax: Maximum Observed Plasma Concentration for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part B, tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part B, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours After Dosing for E2730
大体时间:Day 1: 0-24 hours; Day 22: 0-24 hours
Day 1: 0-24 hours; Day 22: 0-24 hours
Part B, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part B, AUC(0-72h): Area Under the Plasma Concentration-time Curve From Zero Time to 72 Hours After Dosing for E2730
大体时间:Day 1: 0-72 hours; Day 22: 0-72 hours
Day 1: 0-72 hours; Day 22: 0-72 hours
Part B, AUC(0-inf): Area Under the Plasma Concentration-time Curve From Zero Time Extrapolated to Infinite Time for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part B, t1/2: Terminal Elimination Phase Half-life for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part A: Geometric Mean Ratio of Cmax Between the Healthy Japanese and non-Japanese Participants for E2730
大体时间:Day 1: 0-24 hours; Day 18: 0-336 hours
Day 1: 0-24 hours; Day 18: 0-336 hours
Part A: Geometric Mean Ratio of AUC(0-24) Between the Healthy Japanese and non-Japanese Participants for E2730
大体时间:Day 1: 0-24 hours; Day 18: 0-24 hours
Day 1: 0-24 hours; Day 18: 0-24 hours
Part B: Geometric Mean Ratio of Cmax Between the Fasted and fed State for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part B: Geometric Mean Ratio of AUC(0-t) Between the Fasted and fed State for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours
Part B: Geometric Mean Ratio of AUC(0-72h) Between the Fasted and fed State for E2730
大体时间:Day 1: 0-72 hours; Day 22: 0-72 hours
Day 1: 0-72 hours; Day 22: 0-72 hours
Part B: Geometric Mean Ratio of AUC(0-inf) Between the Fasted and fed State for E2730
大体时间:Day 1: 0-288 hours; Day 22: 0-288 hours
Day 1: 0-288 hours; Day 22: 0-288 hours

次要结果测量

结果测量
措施说明
大体时间
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
大体时间:Baseline, Day 32
Baseline, Day 32
Change From Baseline in Heart Rate (HR)
大体时间:Baseline, Day 32
Baseline, Day 32
Placebo Corrected Change From Baseline in SBP and DBP
大体时间:Baseline, Day 32
Baseline, Day 32
Placebo Corrected Change From Baseline in HR
大体时间:Baseline, Day 32
Baseline, Day 32
Number of Participants With Categorical Outliers for SBP and DBP
大体时间:Baseline up to Day 32
Baseline up to Day 32
Change From Baseline in QT Interval by Fridericia (QTcF)
大体时间:Baseline, Day 32
Baseline, Day 32
Change From Baseline in PR Interval of the ECG (PR), QRS Interval of the ECG (QRS)
大体时间:Baseline, Day 32
Baseline, Day 32
Placebo Corrected Change From Baseline in QTcF, PR and QRS
大体时间:Baseline, Day 32
Baseline, Day 32
Number of Participants With Categorical Outliers for QTcF, HR, PR, and QRS
大体时间:Baseline, Day 32
Baseline, Day 32
Number of Participants With T-wave Morphology Changes
大体时间:Baseline up to Day 32
The T-wave morphology categories includes the following: Normal T-wave (Any positive T-wave not meeting any criterion); Flat T-wave (T amplitude less than (<) 1 millimeter [mm] [either positive or negative] including flat isoelectric line); Notched T-wave (+) (Presence of notch(es) of at least 0.05 millivolt [mV] amplitude on ascending or descending arm of the positive T-wave); Biphasic (T-wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T-waves included); Normal T-wave (-) (T amplitude that is negative, without biphasic T-wave or notches); Notched T-wave (-) (Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T-wave).
Baseline up to Day 32
Number of Participants With Presence of Abnormal U-wave
大体时间:Baseline up to Day 32
Baseline up to Day 32

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2020年12月16日

初级完成 (实际的)

2021年6月23日

研究完成 (实际的)

2021年6月23日

研究注册日期

首次提交

2020年12月15日

首先提交符合 QC 标准的

2020年12月15日

首次发布 (实际的)

2020年12月21日

研究记录更新

最后更新发布 (实际的)

2021年8月26日

上次提交的符合 QC 标准的更新

2021年8月20日

最后验证

2021年8月1日

更多信息

与本研究相关的术语

其他研究编号

  • E2730-A001-013

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

是的

IPD 计划说明

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

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