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A Study to Evaluate the Effects of E2609 on QTc Interval in Healthy Subjects

Phase 1
Completed
Conditions
Healthy Subjects
Interventions
Registration Number
NCT02222324
Lead Sponsor
Eisai Inc.
Brief Summary

This thorough QT (TQT) study will take place in healthy subjects administered single doses of study drug. It will be a randomized, double-blind, placebo and active-controlled, 4-treatment crossover study. Subjects will be randomized in an equal ratio to one of 12 possible treatment sequences. Each treatment sequence will comprise all 4 treatments.

Detailed Description

The study will consist of 2 phases: Prerandomization and Randomization. The Prerandomization Phase will have 2 periods: Screening (up to 27 days) and Baseline Period 1 (1 day). Eligibility will be determined during the Screening Period. The Randomization Phase will consist of 8 periods: Treatment Period 1, Baseline Period 2, Treatment Period 2, Baseline Period 3, Treatment Period 3, Baseline Period 4, Treatment Period 4, and a Follow-Up Period. Each Baseline Period will last 1 day, followed by the corresponding treatment period. On the first day of each treatment period, subjects will receive a single dose of the assigned study drug. During each treatment period, subjects will be required to stay in the clinical unit from the baseline period to 24 hours postdose. Subjects will then be released from the clinic and will undergo a washout interval of at least 13 days, during which time they will return for additional PK sampling.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment APlaceboPlacebo
Treatment BE2609E2609 Low dose
Treatment CE2609E2609 High dose
Treatment DMoxifloxacinMoxifloxacin
Primary Outcome Measures
NameTimeMethod
Change from baseline in QTcF obtained from ECGs extracted from the Holter recordingsUp to 24 hours postdose during each treatment period

Holter recordings are taken from a portable device for continuously monitoring various electrical activity of the cardiovascular system for at least 24 hours. Baseline is defined as the mean of predose QTcF values obtained from ECGs extracted from Holter recordings before dosing during each treatment period.

Secondary Outcome Measures
NameTimeMethod
Change from baseline in ECG recordings: T wave morphologyPredose and then at up to 24 hours postdose in each treatment period

Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.

Pharmacokinetics of E2609: CmaxUp to 84 Days

Maximum drug concentration

Pharmacokinetics of E2609: tmaxUp to 84 Days

Ttime to reach maximum (peak) concentration following drug administration

Change from baseline in ECG recordings: PR intervalPredose and then up to 24 hours postdose in each treatment period

Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.

Change from baseline in ECG recordings: QRS intervalPredose and then up to 24 hours postdose in each treatment period

Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.

Change from baseline in ECG recordings: HRPredose and then up 24 hours postdose in each treatment period

Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.

Change from baseline in ECG recordings: RR intervalPredose and then at up to 24 hours postdose in each treatment period

Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.

Pharmacokinetics of E2609: AUC(0-t)Up to 84 Days

Area under the concentration x time curve from time = 0 to time of last measurable concentration

Pharmacokinetics of E2609: AUC(0-72h)Up to 84 Days

Area under the concentration x time curve from time = 0 to 72 hours postdose

Pharmacokinetics of E2609: AUC(0-inf)Up to 84 Days

Area under the concentration x time curve from time = 0 to infinity

Pharmacokinetics of E2609: t1/2Up to 84 Days

Terminal elimination half-life

Pharmacokinetics of E2609: CL/FUp to 84 Days

Apparent total clearance following extravascular administration

Pharmacokinetics of E2609: Vz/FUp to 84 Days

Apparent volume of distribution following extravascular administration

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