Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742 in Healthy Adult Subjects

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03082235
• Other study ID #: E6742-A001-001
• Status: Completed
• Phase: Phase 1
• Start date: March 3, 2017
• Est. completion date: October 11, 2017

Study information

• Verified date: November 2017
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 11, 2017
• Est. primary completion date: October 11, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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 [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.

• 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

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• E6742
gelatin capsules
• Placebo
gelatin capsules

Locations

Country	Name	City	State
United States	Parexel International	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with any serious adverse event and number of participants with any non-serious adverse event	The number of participants with any serious adverse event and the number of participants with any non-serious adverse event will be reported.	from Screening up to Day 7
Primary	Mean maximum observed concentration (Cmax) of E6742 and the metabolite ER-1132963 in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	Time at which the highest drug concentration occurs (tmax) for E6742 and the metabolite ER-1132963 in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	Area under the concentration-time curve from zero time to 24 hours postdose (AUC[0-24h]) E6742 and the metabolite ER-1132963 in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	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	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	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	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	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	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	Terminal elimination phase half-life (t1/2) for E6742 and the metabolite ER-1132963 in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	Apparent total clearance following extravascular administration (CL/F) for E6742 in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	Apparent volume of distribution at terminal phase (Vz/F) for E6742 in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	AUC metabolite to E6742 ratio following molecular weight correction to E6742 equivalents in plasma	Cohorts 1, 2, 3, 5, and 6: Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose). Cohort 4: In both periods (Treatment Periods 1 [7 days] and 2 [6 days]), Day 1 at predose and 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose; Day 2 (24 and 36 hours postdose); Day 3 (48 hours postdose); Day 4 (72 hours postdose); Day 5 (96 hours postdose); Day 6 (120 hours postdose); Day 7 (144 hours postdose).	Days 1 to 7
Primary	Amount of unchanged drug excreted in urine (Ae) for E6742 and the metabolite ER-1132963	Cohorts 1, 2, 3, 5, and 6: Days 1 to 7: predose and 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose. Cohort 4: Days 1 to 7 (Treatment Period 1): predose and 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose.	Days 1 to 7
Primary	Renal clearance (CLR)	Cohorts 1, 2, 3, 5, and 6: Days 1 to 7: predose and 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose. Cohort 4: Days 1 to 7 (Treatment Period 1): predose and 0 to 4, >4 to 8, >8 to 12, >12 to 24, >24 to 48, >48 to 72, >72 to 96, >96 to 120, and >120 to 144 hours postdose.	Days 1 to 7