title: Effects of Peginesatide Injection on QTc Interval in Healthy Adults.
abstract: 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.
authors.affiliation: Takeda Development Center Americas, Inc. Deerfield, IL, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Czerniak
authors.affiliation: Takeda Development Center Americas, Inc. Deerfield, IL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kukulka
authors.affiliation: Takeda Development Center Americas, Inc. Deerfield, IL, USA.
authors.forename: Jing Tao
authors.initials: JT
authors.lastname: Wu
authors.affiliation: Takeda Development Center Americas, Inc. Deerfield, IL, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
keywords: QTc; QTcF; cardiovascular safety; erythropoiesis-stimulating agent; peginesatide pharmacokinetics