Oritavancin, a new lipoglycopeptide antibiotic: results from a thorough QT study

J Clin Pharmacol. 2010 Aug;50(8):895-903. doi: 10.1177/0091270009355449. Epub 2010 May 19.

Abstract

Oritavancin is a lipoglycopeptide with broad activity against gram-positive bacteria. To exclude an effect on cardiac repolarization, oritavancin was studied in a thorough QT study. In vitro assays have demonstrated a 10-fold safety margin between the concentration that resulted in 50% block of the cardiac potassium current and therapeutic plasma levels in patients and no safety margin for block of the sodium currents. In a parallel-group study, 240 male and female subjects received treatment with either the clinical dose (200 mg intravenously) or a supratherapeutic dose (800 mg intravenously) of oritavancin, placebo, or a positive control (400 mg of oral moxifloxacin). Electrocardiograms were recorded in triplicate at several time points after dosing. The primary end point was the largest baseline-adjusted, placebo-corrected QTcI observed at any point after oritavancin dosing. The study's sensitivity to demonstrate a sufficiently small QTc change was confirmed by the moxifloxacin effect. The baseline-adjusted, placebo-corrected QTcI was between -3 milliseconds and 3 milliseconds after 800 mg of oritavancin, and an effect exceeding 6 milliseconds was confidently excluded. Other electrocardiographic parameters were unaffected by the treatment. It was concluded that oritavancin did not cause QTc prolongation in this thorough QT study.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Area Under Curve
  • Aza Compounds / pharmacokinetics
  • Aza Compounds / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography
  • Female
  • Fluoroquinolones
  • Glycopeptides / adverse effects*
  • Glycopeptides / pharmacokinetics*
  • Glycopeptides / therapeutic use
  • Humans
  • Lipoglycopeptides
  • Male
  • Middle Aged
  • Moxifloxacin
  • Quinolines / pharmacokinetics
  • Quinolines / therapeutic use
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Aza Compounds
  • Fluoroquinolones
  • Glycopeptides
  • Lipoglycopeptides
  • Quinolines
  • oritavancin
  • Moxifloxacin