A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2027 in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: E2027; Drug: E2027 matched placebo

• Registration Number: NCT02873156
• Lead Sponsor: Eisai Inc.

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of multiple ascending oral doses of E2027 in healthy participants.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-10
• Study First Submitted: 2016-08-16
• Study First Submitted QC: 2016-08-16
• Study First Posted: 2016-08-19
• Status Verified: 2017-11
• Primary Completion: 2017-11-29
• Study Completion: 2017-11-29
• Last Update Submitted: 2018-09-06
• Last Update Posted: 2018-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
E2027	E2027	Four sequential cohorts of healthy participants (≥50 years and ≤85 years old) will be treated with multiple ascending doses of E2027 up to the maximum tolerated dose (MTD). A total of 6 participants per cohort will be randomized to E2027.Proposed doses of E2027 are: * Part A Cohort 1: 50 mg (1 × 50 mg capsule) * Cohort 2: 100 mg (2 × 50 mg capsules) * Cohort 3: 200 mg (4 × 50 mg capsules) * Cohort 4: 400 mg (8 × 50 mg capsules) * Cohort 6: 25 mg (5 × 5 mg capsules) Part B * Cohort 5: 400 mg (8 × 50 mg capsule) Part C: • Cohort 7: 50 mg (1 × 50 mg capsules) Part D: * Cohort 8: 5 mg (1 × 5 mg capsules) * Cohort 9: 10 mg (2 × 5 mg capsules)
Placebo	E2027 matched placebo	Four sequential cohorts of healthy participants (≥50 years and ≤85 years old) will be treated with multiple ascending doses of E2027 matched placebo up to the MTD. A total of 2 participants per cohort will be randomized to E2027 matched placebo.

Primary Outcome Measures

Name	Time	Method
Maximum drug concentration (Cmax)	Day 1 and Day 14	Blood samples will be collected on Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14).
Mean predose drug concentration (Cmin)	Predose on Days 2, 4, 6, 8, 10, 12, 13, and 14
Mean ratio of cerebrospinal fluid (CSF) : plasma concentrations	Day -2 (time-matched to the Day 13 lumbar puncture [LP]) and Day 13 (predose)
Mean time to reach maximum (peak) drug concentration (tmax)	Day 1 and Day 14	Blood samples will be collected on Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14).
Mean apparent volume of distribution at steady state (Vss/F)	Day 14	Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean area under the concentration-time curve from zero time to 24 hours postdose (AUC(0-24h))	Day 1 and Day 14	Blood samples will be collected on Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14).
Mean terminal elimination half-life (t1/2)	Day 14	Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean apparent clearance at steady state (CLss/F)	Day 14	Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean area under the concentration-time curve from zero time extrapolated to infinity (AUC(0-inf))	Day 14	Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Average steady state drug concentration (Css,av)	Day 14	Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean accumulation ratio (Rac) (Day 14: Day 1) for AUC(0-24h), Cmax and Cmin	Day 1 and Day 14	Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14)
Mean peak-trough fluctuation ratio (PTF)	Day 14	Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).

Secondary Outcome Measures

Name	Time	Method
Percentage change from Baseline in pharmacodynamic measure	Day -2 (baseline with no drug) to Day 13 (on drug)
Change from baseline in Observed Fridericia's Correction Formula (QTcF)	Days -1, 1, and 14

Trial Locations

Locations (1)

California Clinical Trials Medical Group; 🇺🇸 Glendale, California, United States