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A thorough QT study to assess the effects of tbo-filgrastim on cardiac repolarization in healthy subjects.

Adar L, Avisar N, Lammerich A, Kleiman RB, Spiegelstein O - Drug Des Devel Ther (2015)

Bottom Line: Concentration-effect modeling showed no evidence of an effect of tbo-filgrastim on cardiac repolarization.Tbo-filgrastim produced no clinically significant changes in other electrocardiogram parameters.Tbo-filgrastim was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: R&D, Teva Pharmaceutical Industries Ltd, Netanya, Israel.

ABSTRACT
Tbo-filgrastim is a recombinant human granulocyte colony-stimulating factor approved by the US Food and Drug Administration to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. We assessed the effect of tbo-filgrastim on cardiac conduction and repolarization in healthy subjects. A three-arm, parallel-group, active- and placebo-controlled, double-blind study randomized healthy adults to a single 5 μg/kg intravenous tbo-filgrastim infusion, a single intravenous placebo infusion, or a single 400 mg moxifloxacin oral dose. The primary end point was placebo-corrected time-matched change from baseline in QT interval corrected using a QT individual correction (QTcI) method. Secondary end points included heart rate, PR interval, QRS duration, change in electrocardiogram patterns, correlation between QTcI change from baseline (milliseconds) and tbo-filgrastim serum concentrations, and safety variables. A total of 145 subjects were enrolled (50 tbo-filgrastim, 50 placebo, 45 moxifloxacin). Peak placebo-corrected change from baseline for QTcI with tbo-filgrastim was 3.5 milliseconds, with a two-sided 95% upper confidence interval of 7.2 milliseconds, demonstrating no signal for any tbo-filgrastim effect on QTc. Concentration-effect modeling showed no evidence of an effect of tbo-filgrastim on cardiac repolarization. Tbo-filgrastim produced no clinically significant changes in other electrocardiogram parameters. Tbo-filgrastim was well tolerated.

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Related in: MedlinePlus

Placebo-corrected change from baseline QT individual correction method (QTcI; milliseconds [ms]) versus mean tbo-filgrastim serum concentration.Note: Estimates from the mixed-effects model regression (subjects with both pharmacokinetic and cardiac end point data).
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f3-dddt-9-2653: Placebo-corrected change from baseline QT individual correction method (QTcI; milliseconds [ms]) versus mean tbo-filgrastim serum concentration.Note: Estimates from the mixed-effects model regression (subjects with both pharmacokinetic and cardiac end point data).

Mentions: The concentration-effect analysis demonstrated no relationship between the concentration of tbo-filgrastim and the placebo-corrected change from baseline in QTcI, with a P-value for the slope of the serum-concentration effect on ΔΔQTcI of 0.07. The slope for QTcI in the tbo-filgrastim treatment group was flat, and the overall predicted placebo- and baseline-corrected QTcI value at Cmax was −0.22 milliseconds (Figure 3). These data did not support any effect of tbo-filgrastim on cardiac repolarization.


A thorough QT study to assess the effects of tbo-filgrastim on cardiac repolarization in healthy subjects.

Adar L, Avisar N, Lammerich A, Kleiman RB, Spiegelstein O - Drug Des Devel Ther (2015)

Placebo-corrected change from baseline QT individual correction method (QTcI; milliseconds [ms]) versus mean tbo-filgrastim serum concentration.Note: Estimates from the mixed-effects model regression (subjects with both pharmacokinetic and cardiac end point data).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440426&req=5

f3-dddt-9-2653: Placebo-corrected change from baseline QT individual correction method (QTcI; milliseconds [ms]) versus mean tbo-filgrastim serum concentration.Note: Estimates from the mixed-effects model regression (subjects with both pharmacokinetic and cardiac end point data).
Mentions: The concentration-effect analysis demonstrated no relationship between the concentration of tbo-filgrastim and the placebo-corrected change from baseline in QTcI, with a P-value for the slope of the serum-concentration effect on ΔΔQTcI of 0.07. The slope for QTcI in the tbo-filgrastim treatment group was flat, and the overall predicted placebo- and baseline-corrected QTcI value at Cmax was −0.22 milliseconds (Figure 3). These data did not support any effect of tbo-filgrastim on cardiac repolarization.

Bottom Line: Concentration-effect modeling showed no evidence of an effect of tbo-filgrastim on cardiac repolarization.Tbo-filgrastim produced no clinically significant changes in other electrocardiogram parameters.Tbo-filgrastim was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: R&D, Teva Pharmaceutical Industries Ltd, Netanya, Israel.

ABSTRACT
Tbo-filgrastim is a recombinant human granulocyte colony-stimulating factor approved by the US Food and Drug Administration to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. We assessed the effect of tbo-filgrastim on cardiac conduction and repolarization in healthy subjects. A three-arm, parallel-group, active- and placebo-controlled, double-blind study randomized healthy adults to a single 5 μg/kg intravenous tbo-filgrastim infusion, a single intravenous placebo infusion, or a single 400 mg moxifloxacin oral dose. The primary end point was placebo-corrected time-matched change from baseline in QT interval corrected using a QT individual correction (QTcI) method. Secondary end points included heart rate, PR interval, QRS duration, change in electrocardiogram patterns, correlation between QTcI change from baseline (milliseconds) and tbo-filgrastim serum concentrations, and safety variables. A total of 145 subjects were enrolled (50 tbo-filgrastim, 50 placebo, 45 moxifloxacin). Peak placebo-corrected change from baseline for QTcI with tbo-filgrastim was 3.5 milliseconds, with a two-sided 95% upper confidence interval of 7.2 milliseconds, demonstrating no signal for any tbo-filgrastim effect on QTc. Concentration-effect modeling showed no evidence of an effect of tbo-filgrastim on cardiac repolarization. Tbo-filgrastim produced no clinically significant changes in other electrocardiogram parameters. Tbo-filgrastim was well tolerated.

No MeSH data available.


Related in: MedlinePlus