QT/QTc assessment of ceftobiprole in a single-dose study
Abstract number: 1733_281
Balis D., Strauss R., Murthy B., Tiian H., Noel G.
Objectives: Delayed cardiac repolarisation is a potential side effect of some non-antiarrhythmic drugs. Because delayed cardiac repolarisation has been associated with the increased risk of serious and potentially life-threatening arrhythmia, rigorous characterisation of a drug's effect on the QT/QTc interval is warranted. The current study was conducted to evaluate the effects of ceftobiprole on QT/QTc interval.
Methods: This was a randomised, double-blind, placebo- and positive-controlled, double-dummy, 4-way crossover, single-centre study of ceftobiprole medocaril at therapeutic (500 mg) and supratherapeutic (1000 mg) doses intravenously infused over 2 h in healthy adult volunteers. Sixty subjects received either a single dose of ceftobiprole medocaril (500 mg or 1000 mg) or matching placebo intravenous (i.v.) infusion on Day 1. In addition, the subjects received either a single dose of moxifloxacin 400 mg as a positive control or a matching placebo as oral administration prior to i.v. infusion on Day 1. Serial 12-lead ECGs were measured on Day 1 (baseline) and Day 1 (post-dose). Fridericia correction was used as the primary correction method for statistical evaluation of serial ECG data.
Results: The upper limits of the 90% confidence intervals for difference in mean change in QTcF (QTc interval using Fridericia correction formula) between ceftobiprole 1000 mg and placebo (change in QTcF) were below 10 ms at all time points. The same result was demonstrated for change in QTcF between ceftobiprole 500 mg and placebo. Therefore, this analysis establishes the noninferiority of ceftobiprole to placebo with respect to QT/QTc interval duration. The lower limit of 90% confidence intervals for the difference in mean change in QTcF between moxifloxacin and placebo was above zero for all time points between 1.25 and 24 h, with a mean difference of 5.5 ms to 13.1 ms. Results from this analysis establish assay sensitivity.
Conclusion: In this QT/QTc study conducted in healthy adult subjects, the effect of single i.v. administrations of ceftobiprole at therapeutic (500 mg) and supratherapeutic (1000 mg) doses on QT/QTc prolongation was comparable to placebo.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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