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

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

RCT Entities:   Population Interventions Outcomes