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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
8 placebo tablets matching E2609
E2609 will be administered as 8 tablets
Administered as 1 tablet with 7 tablets of placebo matching E2609
Unnamed facility
San Antonio, Texas, United States
Change from baseline in QTcF obtained from ECGs extracted from the Holter recordings
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.
Time frame: Up to 24 hours postdose during each treatment period
Change from baseline in ECG recordings: PR interval
Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
Time frame: Predose and then up to 24 hours postdose in each treatment period
Change from baseline in ECG recordings: QRS interval
Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
Time frame: Predose and then up to 24 hours postdose in each treatment period
Change from baseline in ECG recordings: HR
Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
Time frame: Predose and then up 24 hours postdose in each treatment period
Change from baseline in ECG recordings: RR interval
Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
Time frame: Predose and then at up to 24 hours postdose in each treatment period
Change from baseline in ECG recordings: T wave morphology
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Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
Time frame: Predose and then at up to 24 hours postdose in each treatment period
Pharmacokinetics of E2609: Cmax
Maximum drug concentration
Time frame: Up to 84 Days
Pharmacokinetics of E2609: tmax
Ttime to reach maximum (peak) concentration following drug administration
Time frame: Up to 84 Days
Pharmacokinetics of E2609: AUC(0-t)
Area under the concentration x time curve from time = 0 to time of last measurable concentration
Time frame: Up to 84 Days
Pharmacokinetics of E2609: AUC(0-72h)
Area under the concentration x time curve from time = 0 to 72 hours postdose
Time frame: Up to 84 Days
Pharmacokinetics of E2609: AUC(0-inf)
Area under the concentration x time curve from time = 0 to infinity
Time frame: Up to 84 Days
Pharmacokinetics of E2609: t1/2
Terminal elimination half-life
Time frame: Up to 84 Days
Pharmacokinetics of E2609: CL/F
Apparent total clearance following extravascular administration
Time frame: Up to 84 Days
Pharmacokinetics of E2609: Vz/F
Apparent volume of distribution following extravascular administration
Time frame: Up to 84 Days