Effects of peginesatide injection on QTc interval in healthy adults. Issue 6 (20th October 2014)

• Record Type: Journal Article
• Authors: Czerniak, Richard; Kukulka, Michael; Wu, Jing Tao; Qiu, Ping
• Is Part Of: Clinical pharmacology in drug development. Volume 3:Issue 6(2014:Nov./Dec.)
• Page Start: 449
• Page End: 455
• Publication Date: 2014-10-20
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.141
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd141-sec-0001" sec-type="section"> <p>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, <italic>P</italic> = 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.</p> </sec> </abstract>