A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730 in Healthy Participants

NCT03451890 | Completed Phase 1 FDA Drug

• 1 other identifier: E2730-A001-002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted to evaluate the safety, tolerability, and pharmacokinetics of single ascending oral doses of E2730 in healthy adult participants.

Conditions

Healthy Participants

Keywords

Healthy participants; E2730; Pharmacokinetics

Outcome Measures

Primary Outcomes (14)

• Mean maximum observed concentration (Cmax) for E2730 and the N-acetyl metabolite (M1) in plasma

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Time at which the highest drug concentration (tmax) occurs for E2730 and the N-acetyl metabolite (M1) in plasma

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean area under the concentration-time curve from zero time to 24 hours after dosing (AUC[0-24h]) for E2730 and the N-acetyl metabolite (M1) in plasma

  predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours postdose on Day 1; Day 2 (24 hours postdose)

• Mean area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t]) for E2730 and the N-acetyl metabolite (M1) in plasma

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean area under the concentration-time curve from zero time to 72 hours after dosing (AUC[0-72h]) for E2730 and the N-acetyl metabolite (M1) in plasma

  predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours postdose on Day 1; thereafter on Day 2 (24 hours postdose), Day 3 (48 hours postdose), Day 4 (72 hours postdose)

• Mean area under the concentration-time curve from zero time extrapolated to infinite time (AUC[0-inf]) for E2730 and the N-acetyl metabolite (M1) in plasma

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean terminal elimination phase half-life (t1/2) for E2730 and the N-acetyl metabolite (M1) in plasma

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean apparent total clearance following oral administration (CL/F) of E2730

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean apparent volume of distribution at terminal phase (Vz/F) for E2730 in plasma

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean metabolite ratio (%) (MRP) in plasma

  Metabolite ratio (%) is calculated as the ratio of plasma AUC(0-inf) of a metabolite to a parent following molar correction.

  predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours (hr) postdose (PD) on Day 1; thereafter on Day 2 (24 hr PD), Day 3 (48 hr PD), Day 4 (72 hr PD), Day 5 (96 hr PD), Day 6 (120 hr PD), Day 7 (144 hr PD), and Day 10 (216 hr PD), and Day 13 (288 hr PD)

• Mean amount of unchanged drug excreted (Ae) in urine for E2730 and the N-acetyl metabolite (M1)

  Days 1 through Days 7 at the following intervals: predose; 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

• Renal clearance (CLR) of E2730 and the N-acetyl metabolite (M1)

  Days 1 through Days 7 at the following intervals: predose; 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

• Percent (%) of administered dose of E2730 and the N-acetyl metabolite (M1) excreted in urine

  Days 1 through Days 7 at the following intervals: predose; 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

• Mean metabolite ratio (%) (MRP) for E2730 and the N-acetyl metabolite (M1) in urine

  Days 1 through Days 7 at the following intervals: predose; 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

Study Arms (8)

Cohort 1: E2730 40 mg

EXPERIMENTAL

Participants will receive a single oral dose of E2730 40 milligrams (mg) under fasted conditions.

Drug: E2730

Cohort 1: Matching placebo

PLACEBO COMPARATOR

Participants will receive a single oral dose of matching placebo under fasted conditions.

Drug: Placebo

Cohort 2: E2730 80 mg

EXPERIMENTAL

Participants will receive a single oral dose of E2730 80 mg under fasted conditions.

Drug: E2730

Cohort 2: Matching placebo

PLACEBO COMPARATOR

Participants will receive a single oral dose of matching placebo under fasted conditions.

Drug: Placebo

Cohort 3: E2730 120 mg

EXPERIMENTAL

Participants will receive a single oral dose of E2730 120 mg under fasted conditions.

Drug: E2730

Cohort 3: Matching placebo

PLACEBO COMPARATOR

Participants will receive a single oral dose of matching placebo under fasted conditions.

Drug: Placebo

Cohort 4: E2730 160 mg

EXPERIMENTAL

Participants will receive a single oral dose of E2730 160 mg under fasted conditions.

Drug: E2730

Cohort 4: Matching placebo

PLACEBO COMPARATOR

Participants will receive a single oral dose of matching placebo under fasted conditions.

Drug: Placebo

Interventions

E2730 DRUG

oral capsule

Cohort 1: E2730 40 mg; Cohort 2: E2730 80 mg; Cohort 3: E2730 120 mg; Cohort 4: E2730 160 mg

Placebo DRUG

oral capsule

Cohort 1: Matching placebo; Cohort 2: Matching placebo; Cohort 3: Matching placebo; Cohort 4: Matching placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period or 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.
• Participants with history of seizures, including those experienced in childhood
• Any history of gastrointestinal surgery that may affect pharmacokinetic profiles of E2730, e.g., hepatectomy, nephrectomy, and digestive organ resection
• A prolonged QT/QTc interval (QTcF \>450 milliseconds) demonstrated by a repeated ECG at Screening or Baseline (based on average of triplicate ECGs). A history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval
• Persistent systolic blood pressure (BP) \>139 or \<90 millimeters of mercury (mmHg) or diastolic BP \>89 or \<50 mmHg at Screening or Baseline
• Left bundle branch block
• History of myocardial infarction or active ischemic heart disease
• 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, or those who have a positive drug test at Screening or Baseline
• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Collaborative Neuroscience Network

Long Beach, California, 90806, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 2, 2018
• Study Start: February 9, 2018
• Primary Completion: September 26, 2018
• Study Completion: September 26, 2018
• Last Updated: March 4, 2019

Record last verified: 2018-02

Locations

US (1)