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Effects of Peginesatide Injection on QTc Interval in Healthy Adults.

Czerniak R, Kukulka M, Wu JT, Qiu P - Clin Pharmacol Drug Dev (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Takeda Development Center Americas, Inc. Deerfield, IL, USA.

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.

No MeSH data available.


(A) Study flow diagram. (B) Treatment sequences. Regimen A: peginesatide placebo (0.9% sodium chloride) plus moxifloxacin placebo. Regimen B: peginesatide injection plus moxifloxacin placebo. Regimen C: peginesatide placebo plus moxifloxacin.
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fig01: (A) Study flow diagram. (B) Treatment sequences. Regimen A: peginesatide placebo (0.9% sodium chloride) plus moxifloxacin placebo. Regimen B: peginesatide injection plus moxifloxacin placebo. Regimen C: peginesatide placebo plus moxifloxacin.

Mentions: This was a Phase 1, single-dose, randomized, double-blind, placebo- and positive-controlled, three-period crossover study. Each treatment period consisted of a 3-day confinement period, with the dosing days separated by 14-day washout intervals (Figure 1A). Adverse events were monitored from screening to 30 days after the last dose of study drug.


Effects of Peginesatide Injection on QTc Interval in Healthy Adults.

Czerniak R, Kukulka M, Wu JT, Qiu P - Clin Pharmacol Drug Dev (2014)

(A) Study flow diagram. (B) Treatment sequences. Regimen A: peginesatide placebo (0.9% sodium chloride) plus moxifloxacin placebo. Regimen B: peginesatide injection plus moxifloxacin placebo. Regimen C: peginesatide placebo plus moxifloxacin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489320&req=5

fig01: (A) Study flow diagram. (B) Treatment sequences. Regimen A: peginesatide placebo (0.9% sodium chloride) plus moxifloxacin placebo. Regimen B: peginesatide injection plus moxifloxacin placebo. Regimen C: peginesatide placebo plus moxifloxacin.
Mentions: This was a Phase 1, single-dose, randomized, double-blind, placebo- and positive-controlled, three-period crossover study. Each treatment period consisted of a 3-day confinement period, with the dosing days separated by 14-day washout intervals (Figure 1A). Adverse events were monitored from screening to 30 days after the last dose of study drug.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Takeda Development Center Americas, Inc. Deerfield, IL, USA.

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.

No MeSH data available.