Phase 1 Study to Assess the Effects of EVP-6124 on the QT/QTc Interval in Healthy Subjects (TQT)
The purpose of this study is to evaluate the effect of EVP-6124 at therapeutic and supratherapeutic concentrations on cardiac repolarization in healthy subjects.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blind, Placebo- and Active-controlled, 3-way Crossover, Phase 1 Study to Evaluate the Effect of EVP-6124 at Therapeutic and Supratherapeutic Concentrations Following a 2-dose EVP-6124 Regimen on the QT Interval in Healthy Male and Female Subjects.|
- Change-from-baseline in individual corrected QTc (ΔQTcI) for EVP-6124 vs. placebo [ Time Frame: Day 1: predose to 20 hours postdose; Day 2 predose to 168 hours postdose ] [ Designated as safety issue: Yes ]
Change-from-baseline in Fridericia's correction QTc (ΔQTcF) and change-from-baseline in Bazett's correction QTc (ΔQTcB) will be secondary variables.
The placebo-corrected baseline-adjusted QTc (ΔΔQTc), calculated as differences between time-matched mean change-from-baseline QTc values obtained on Day 1 (low dose) and on Day 2 (high dose) of the EVP-6124 treatment relative to the corresponding QTc values obtained on Day 1 and Day 2 of the placebo treatment, will be evaluated to quantify the effect of EVP-6124 on cardiac repolarization.
- Change-from-baseline in individual corrected QTc (ΔQTcI) for positive control vs. placebo [ Time Frame: Day 1: predose to 20 hours postdose ] [ Designated as safety issue: No ]The placebo-corrected baseline-adjusted QTc (ΔΔQTc), calculated as differences between time-matched mean change-from-baseline QTc values obtained on Day 1 of the moxifloxacin treatment relative to QTc values obtained on Day 1 of the placebo treatment, will be evaluated to establish assay sensitivity.
- Safety and tolerability of EVP-6124 at low dose and high doses [ Time Frame: Day -1 through follow-up (5 to 10 days after discharge) ] [ Designated as safety issue: Yes ]All AEs (adverse experiences) spontaneously reported by subjects and/or observed by investigator and evaluation of physical examinations, prior and concomitant medications, clinical laboratory tests, ECGs, and vital signs measurements.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||January 2013|
|Estimated Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
A single oral low dose of EVP-6124 in cranberry juice (180 mL) administered on Day 1 and a high dose of EVP-6124 in cranberry juice (180 mL) administered on Day 2.
Placebo Comparator: Placebo
Cranberry juice (180 mL)
Cranberry juice only (180 mL) administered orally on both Day 1 and Day 2.
|Active Comparator: Moxifloxacin||
A moxifloxacin 400 mg tablet administered orally on Day 1
Other Name: Avelox
Subjects will be randomized to six treatment sequences of 10 subjects each. Subjects will be admitted to the clinic on Day -1 before dosing. Each of the EVP-6124 and placebo treatment periods (blinded) will include a 10-day/9-night confinement to the Clinical Pharmacology Unit (CPU) with study drugs being administered on Day 1 and Day 2. The moxifloxacin treatment period (open-label) will include a 3-day/2-night confinement to the CPU with moxifloxacin administration on Day 1.
The study will include 2 washout periods in which each washout starts from the time of the last dose of the preceding treatment period to the first dose of the next treatment period. The washouts following the EVP-6124 or placebo treatments will be 30 days while the washout following the moxifloxacin treatment will be 7 days. Follow-up visit (5 to 10 days following discharge from the CPU).