Effects of Peginesatide Injection on QTc Interval in Healthy Adults.

A single-dose, randomized, double-blind, placebo- and positive-controlled, three-period crossover study was conducted to evaluate the effect of peginesatide injection on QT interval in healthy adults. Subjects received single doses of placebo, peginesatide injection 0.1 mg/kg intravenous, or moxifloxacin 400 mg during three treatment periods, separated by 14-day washout intervals. ECG recordings and blood samples for peginesatide and moxifloxacin plasma concentrations were collected prior to dosing and through 22 hours postdose. QT intervals were measured with a high resolution manual on-screen caliper method. The study endpoint was the mean difference between peginesatide and placebo in baseline-adjusted corrected QT interval (ddQTc). The maximum upper bound of the one-sided 95% CI was 2.2 milliseconds at 0.75 hours for Fridericia-corrected ddQTc (ddQTcF) and 2.2 milliseconds at 0.25 hours for individual corrected ddQTcI. The linear relationship between ddQTcF and peginesatide concentrations was essentially flat and not statistically significant [slope = 0.001, P = 0.126, 90% CI: (<−0.0005, 0.002)]. Using this model, the projected ddQTcF effect at the observed mean peak plasma concentration is estimated to be 0.9 milliseconds, 90% CI: (−2.0, 0.3 milliseconds). There were no peginesatide-related effects on heart rate, PR interval, or QRS interval. Thus, there is no anticipated cardiovascular effect of peginesatide injection 0.1 mg/kg in patients.