Oritavancin, a new lipoglycopeptide antibiotic: results from a thorough QT study.
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.
Darpo
Borje
B
Department of Clinical Science and Education, Section of Cardiology, Karolinska Institute, South Hospital, Stockholm, Sweden; Pharmaceutical Consultant, Trasthagen 11, SE 18141 Lidingö, Sweden. borje.darpo@telia.com
Lee
Sun K
SK
Moon
Thomas E
TE
Sills
Nancy
N
Mason
Jay W
JW
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001372:Aza Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D006020:Glycopeptides / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult; D014640:Vancomycin / Q000031:analogs & derivatives
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D000077266:Moxifloxacin; D011804:Quinolines; C100708:oritavancin; D014640:Vancomycin