Study to Assess the Safety, Tolerability, and Pharmacokin... | NCT03054194

Status Module

Label	Type	Description	Intervention Names
Cohort 1: Dose 1 E2730	Experimental	Participants will receive Dose 1 of oral E2730 on Day 1.	Drug: E2730
Cohort 1: Matching placebo	Placebo Comparator	Participants will receive matching oral placebo on Day 1.	Drug: Placebo
Cohort 2: Dose 2 E2730	Experimental	Participants will receive Dose 2 of oral E2730 on Day 1.	Drug: E2730
Cohort 2: Matching placebo	Placebo Comparator	Participants will receive oral matching placebo on Day 1.	Drug: Placebo
Cohort 3: Dose 3 E2730	Experimental	Participants will receive Dose 3 of oral E2730 on Day 1.	Drug: E2730
Cohort 3: Matching placebo	Placebo Comparator	Participants will receive oral matching placebo on Day 1.

Name	Type	Description	Arm Group Labels	Other Names
E2730	Drug	capsules	Cohort 1: Dose 1 E2730 Cohort 2: Dose 2 E2730 Cohort 3: Dose 3 E2730

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of participants with any serious adverse event and number of participants with any non-serious adverse event	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.	up to Day 10 (Follow-up/Early Termination)
Number of participants with an abnormal, clinically significant hematology parameter value	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.	Screening; Baseline; Days 2 and 5; Day 10 (Follow-up/Early Termination)
Number of participants with an abnormal, clinically significant blood chemistry parameter value	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.	Screening; Baseline; Days 2 and 5; Day 10 (Follow-up/Early Termination)
Number of participants with an abnormal, clinically significant urine value

Secondary Outcomes

Measure	Description	Time Frame
Mean change from Baseline in blood pressure (BP) using ambulatory BP monitoring (ABPM)	Blood pressure will be measured after the participant has been supine for 10 minutes. At Baseline and at subsequent time points through 24 hours postdose, after supine measurements are completed, participants will be asked to stand up for 2 minutes and BP will then be measured in the standing position. All BP measurements should be performed on the same arm, preferably by the same person. Continuous Mean change from Baseline is calculated as the post-Baseline visit value minus the Baseline value.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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)