临床试验/NCT03054194

NCT03054194已完成1 期

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730

Eisai Inc.1 个研究点分布在 1 个国家目标入组 8 人开始时间: 2017年1月31日最近更新: 2018年9月7日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Eisai Inc.
入组人数: 8
试验地点: 1
主要终点: Number of participants with any serious adverse event and number of participants with any non-serious adverse event

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Study E2730-A001-001 is a first-in-human, sequential ascending single dose, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single oral dose of E2730 in healthy participants.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Triple (Participant, Investigator, Outcomes Assessor)

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

•Non-smoking, male or female, age ≥18 years and ≤55 years old at the time of informed consent (note: to be considered non-smokers, participants must have discontinued smoking for at least 4 weeks before dosing)
•Body mass index (BMI) ≥18 and <32 kilograms per meters squared (kg/m^2) at Screening

排除标准

•Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
•Females who are breastfeeding or pregnant at Screening or Baseline (documented by a negative beta human chorionic gonadotropin [β-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). A negative urine pregnancy test is required before the administration of the first dose per cohort.
•Females of childbearing potential who:
•Had unprotected sexual intercourse within 30 days before study entry and do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double barrier method [such as condom plus diaphragm with spermicide] or have a vasectomized partner with confirmed azoospermia but hormonal contraceptives are not permitted) throughout the entire study period and for 28 days after study drug discontinuation
•Are currently abstinent, and do not agree to use a double barrier method (as described above) or refrain from sexual activity during the study period or for 28 days after study drug discontinuation
•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).
•Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 3 months after study drug discontinuation.
•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, or participants who have a congenital abnormality in metabolism)
•Any history of seizures, including those experienced in childhood
•Any history of gastrointestinal surgery that may affect pharmacokinetic profiles of E2730 (eg, hepatectomy, nephrectomy, digestive organ resection) at Screening
•Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, electrocardiogram (ECG) finding, or laboratory test results that require medical treatment at Screening or Baseline
•A prolonged QT/QT corrected (QTc) interval (QC interval corrected using Fridericia's formula [QTcF] >450 milliseconds) demonstrated on ECG at Screening or Baseline (based on average of triplicate ECGs). A history of risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval
•Left bundle branch block at Screening or Baseline
•Persistent systolic blood pressure (BP) >130 or <100 millimeters of mercury (mmHg) or diastolic BP >85 or <50 mmHg at Screening or Baseline
•Persistent heart rate less than 50 beats/min or more than 100 beats/min at Screening or Baseline
•History of myocardial infarction, ischemic heart disease, or cardiac failure at Screening
•History of clinically significant arrhythmia or uncontrolled arrhythmia
•Known history of clinically significant drug allergy at Screening or Baseline
•Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline
•Known to be human immunodeficiency virus positive at Screening
•Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening
•History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive drug test (including cannabinoids) or alcohol test at Screening or Baseline
•Intake of caffeinated beverages or food within 72 hours before dosing
•Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug-metabolizing enzymes and transporters (eg, alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussel's sprouts, mustard], and charbroiled meats) within 1 week before dosing
•Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing
•Use of prescription drugs within 4 weeks before dosing
•Intake of over-the-counter (OTC) medications within 2 weeks before dosing
•Currently enrolled in another clinical study or used any investigational drug or device within 30 days or 5 half-lives, whichever is longer, preceding informed consent
•Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing
•Engagement in strenuous exercise within 2 weeks before check-in (eg, marathon runners, weight lifters)

研究组 & 干预措施

Cohort 1: Matching placebo

Placebo Comparator

Participants will receive matching oral placebo on Day 1.

干预措施: Placebo (Drug)

Cohort 2: Matching placebo

Placebo Comparator

Participants will receive oral matching placebo on Day 1.

干预措施: Placebo (Drug)

Cohort 3: Matching placebo

Placebo Comparator

Participants will receive oral matching placebo on Day 1.

干预措施: Placebo (Drug)

Cohort 1: Dose 1 E2730

Experimental

Participants will receive Dose 1 of oral E2730 on Day 1.

干预措施: E2730 (Drug)

Cohort 2: Dose 2 E2730

Experimental

Participants will receive Dose 2 of oral E2730 on Day 1.

干预措施: E2730 (Drug)

Cohort 3: Dose 3 E2730

Experimental

Participants will receive Dose 3 of oral E2730 on Day 1.

干预措施: E2730 (Drug)

结局指标

主要结局

Number of participants with any serious adverse event and number of participants with any non-serious adverse event

时间窗: up to Day 10 (Follow-up/Early Termination)

An adverse event is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious adverse event is defined as any adverse event occurring at any dose that results in any of the following outcomes: results in death; is life threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life function; results in a congenital anomaly/birth defect; or can be defined as any other important medical event.

Number of participants with an abnormal, clinically significant hematology parameter value

时间窗: Screening; Baseline; Days 2 and 5; Day 10 (Follow-up/Early Termination)

Participants will fast for at least 4 hours before blood is drawn for the assessment of hematocrit, hemoglobin, platelets, red blood cell (RBC) count, and white blood cell (WBC) count with differential (basophils, eosinophils, lymphocytes, monocytes, neutrophils). Clinical significance will be determined by the Investigator.

Number of participants with an abnormal, clinically significant blood chemistry parameter value

时间窗: Screening; Baseline; Days 2 and 5; Day 10 (Follow-up/Early Termination)

Participants will fast for at least 4 hours before blood is drawn for the assessment of electrolytes (chloride, potassium, sodium); liver function test parameters (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transpeptidase, direct bilirubin, total bilirubin); renal function test parameters (blood urea/blood urea nitrogen, creatinine); and other parameters such as albumin, calcium, cholesterol, globulin, glucose, lactate dehydrogenase, phosphorus, total protein, triglycerides, and uric acid. Clinical significance will be determined by the Investigator.

Number of participants with an abnormal, clinically significant urine value

时间窗: Screening; Baseline; Days 2 and 5; Day 10 (Follow-up/Early Termination)

Urinalysis will be performed to determine abnormalities in the presence of bacteria, casts, crystals, epithelial cells, glucose, ketones, occult blood, pH, protein, RBCs, specific gravity, and WBCs in urine. Clinical significance will be determined by the Investigator.

Number of participants with an abnormal, clinically significant vital sign value

时间窗: up to Day 10 (Follow-up/Early Termination)

Vital sign measurements (ie, systolic and diastolic blood pressure \[BP\] \[millimeters of mercury (mmHg)\], pulse \[beats per minute\], respiratory rate \[breaths per minute\], and body temperature \[centigrade\]) will be obtained in the supine position by a validated method. Clinical significance will be determined by the Investigator.

Mean change from Baseline in weight

时间窗: Screening; Baseline; Day 10 (Follow-up/Early Termination)

Weight (kilograms \[kg\]) will be obtained by a validated method.

Number of participants with an abnormal, clinically significant electrocardiogram (ECG) parameter value

时间窗: Screening; Baseline; up to Day 10 (Follow-up/Early Termination)

An ECG is a record or display of a person's heartbeat produced by electrocardiography. The Holter device will be used for ECG recording. Monitoring will begin at 24 hours before dosing. Clinical significance will be determined by the Investigator.

Number of participants with an abnormal, clinically significant physical examination parameter value

时间窗: Screening; Baseline; Day 5; Day 10 (Follow-up/Early Termination)

A comprehensive physical examination will include evaluations of the head, eyes, ears, nose, throat, neck, chest (including heart and lungs), abdomen, limbs, skin, and a complete neurological examination. A urogenital examination will only be required in the presence of clinical symptoms related to those regions. For abbreviated physical examinations, health status will be assessed by brief evaluation of the chest (including heart and lungs), abdomen and limbs, and other physical conditions of note. Clinical significance will be determined by the Investigator.

Number of participants with an abnormal, clinically significant neurological parameter value

时间窗: Screening

Abnormalities in neurological parameters due to an increase in inhibitory neurotransmission after E2730 administration will be assessed. Clinical significance will be determined by the Investigator.

Mean maximum observed concentration (Cmax) for E2730 and the N-acetyl metabolite in plasma