Effects of a new antibacterial, telavancin, on cardiac repolarization (QTc interval duration) in healthy subjects.

Telavancin is a rapidly bactericidal antibiotic with multiple mechanisms of action against gram-positive bacteria. Preclinical and early clinical data suggested possible effects on cardiac repolarization requiring the conduct of a definitive evaluation of QT effects in healthy subjects. A total of 160 subjects were randomized into four groups to receive placebo (telavancin vehicle), telavancin at a dose of 7.5 mg/kg or 15 mg/kg, or moxifloxacin 400 mg (positive control). All medications were administered once daily for 3 days as 60-minute IV infusions. Sixteen ECGs were obtained over 24 hours following an infusion of D5W (baseline) and following Day 3 infusions of each medication. ECGs were analyzed digitally in a blinded fashion by a validated core ECG laboratory. The primary endpoint was QT data corrected for heart rate by the Fridericia formula (QTcF). Placebo-corrected mean changes in QTcF values for 7.5 mg/kg telavancin, 15 mg/kg telavancin, and moxifloxacin were 4.1 msec, 4.5 msec, and 9.2 msec, respectively. The mean change from baseline in QTcF for moxifloxacin, which served as the assay-sensitive positive control in the study, helped to establish that telavancin had a minimal effect on QT prolongation. No subject had a QTcF > or = 450 msec, and none experienced clinically significant ECG abnormalities. The telavancin treatment groups were not significantly different from each other. There was no correlation of the magnitude of change in QTc and plasma concentrations of telavancin. Telavancin has a < 5-msec mean effect on cardiac repolarization, with a flat-dose response over a two-fold exposure range.

RCT Entities:   Population Interventions Outcomes