A thorough QT study with dalbavancin: A novel lipoglycopeptide antibiotic for the treatment of acute bacterial skin and skin-structure infections

Abstract

Two hundred healthy subjects were enrolled in a randomised, partially double-blinded, single-centre, parallel design thorough QT study to demonstrate that dalbavancin had no clinical effect on the 12-lead ECG QTc. Fifty patients in each group received either dalbavancin 1000mg intravenous (i.v.), dalbavancin 1500mg i.v. or placebo i.v., each infused over 30min, or 400mg oral moxifloxacin. Ten replicate 12-lead ECGs were extracted at pre-defined time points before and up to 24h post dosing and at corresponding time points during baseline. Dalbavancin did not have an effect on the QTcF interval, and an effect exceeding 10ms could be excluded at all time points after a single i.v. dose of 1000mg and 1500mg. The largest placebo-corrected change-from-baseline QTcF (ΔΔQTcF) was 1.5ms in the 1000mg dalbavancin group at 6h and 0.2ms in the 1500mg group at 24h. A small concentration-dependent effect of dalbavancin on ΔΔQTcF was identified with an estimated negative population slope of −0.0051ms per μg/mL. Assay sensitivity was demonstrated by the effect of 400mg moxifloxacin, which peaked at 2h at ΔΔQTcF of 12.9ms, with the lower bound of the 90% CI of the effect exceeding 5ms at all three pre-defined time points. Dalbavancin did not exert a relevant effect on heart rate or PR or QRS intervals. Dalbavancin in i.v. doses up to 1500mg did not prolong the QTc interval and had no effect on heart rate or PR and QRS intervals.