Clinical trial NCT03082235: Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742 in Healthy Adult Subjects
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Healthy participants
E6742
pharmacokinetics
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-17
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Study E6742-A001-001 is a randomized, double-blind, placebo-controlled, single ascending dose study conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending oral doses of E6742 in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* Nonsmoking, male or female, age ≥18 years and ≤45 years old at the time of informed consent
* Body mass index (BMI) ≥18 and \<32 kilograms per meters squared (kg/m2) at Screening

Exclusion Criteria:

* Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive 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 separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
* 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 and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation). No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation.
* Any history of gastrointestinal surgery that may affect pharmacokinetic (PK) profiles of E6742 (eg, hepatectomy, nephrectomy, digestive organ resection) at Screening
* A prolonged QTcF interval (QTcF \>450 ms) demonstrated on ECG at Screening or Baseline
* Persistent systolic blood pressure \>130 mmHg or diastolic blood pressure \>85 mmHg diastolic at Screening or Baseline Heart rate less than 50 or more than 100 beats/min at Screening or Baseline
* Known history of prolonged QT/QTc interval
* Left bundle branch block
* Known history of myocardial infarction or active ischemic heart disease
* Known history of clinically significant arrhythmia or uncontrolled arrhythmia
* 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
* 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 prior to Screening, or those who have a positive urine drug and alcohol test at Screening or Baseline
* 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) before informed consent
* Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week before dosing

Primary outcomes:
measure: Number of participants with any serious adverse event and number of participants with any non-serious adverse event
timeFrame: from Screening up to Day 7
measure: Mean maximum observed concentration (Cmax) of E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Time at which the highest drug concentration occurs (tmax) for E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Area under the concentration-time curve from zero time to 24 hours postdose (AUC[0-24h]) E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Area under the concentration-time curve from zero time to 72 hours postdose (AUC[0-72h]) for E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t]) for E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Area under the concentration-time curve from zero time extrapolated to infinite time (AUC[0-inf]) for E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Terminal elimination phase half-life (t1/2) for E6742 and the metabolite ER-1132963 in plasma
timeFrame: Days 1 to 7
measure: Apparent total clearance following extravascular administration (CL/F) for E6742 in plasma
timeFrame: Days 1 to 7
measure: Apparent volume of distribution at terminal phase (Vz/F) for E6742 in plasma
timeFrame: Days 1 to 7
measure: AUC metabolite to E6742 ratio following molecular weight correction to E6742 equivalents in plasma
timeFrame: Days 1 to 7
measure: Amount of unchanged drug excreted in urine (Ae) for E6742 and the metabolite ER-1132963
timeFrame: Days 1 to 7
measure: Renal clearance (CLR)
timeFrame: Days 1 to 7
Secondary outcomes:
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Parexel International
state: California
Study officials:
References: