A thorough QT study to assess the effects of tbo-filgrastim on cardiac repolarization in healthy subjects
| Autor: | Liat Adar, Ofer Spiegelstein, Robert Kleiman, Andreas Lammerich, Noa Avisar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
QT interval
Adult Male Filgrastim Moxifloxacin Pharmaceutical Science electrocardiogram Electrocardiography Young Adult QRS complex Double-Blind Method Heart Rate Hematologic Agents Drug Discovery Cardiac conduction medicine Humans Repolarization PR interval Infusions Intravenous Original Research Pharmacology Drug Design Development and Therapy business.industry medicine.disease Anesthesia tbo-filgrastim Female granulocyte colony-stimulating factor business Febrile neutropenia Fluoroquinolones medicine.drug |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Liat Adar,1 Noa Avisar,1 Andreas Lammerich,2 Robert B Kleiman,3 Ofer Spiegelstein1 1R&D, Teva Pharmaceutical Industries Ltd, Netanya, Israel; 2Biosimilars Clinical Development, CPP Teva ratiopharm, Merckle GmbH, Ulm,Germany; 3Global Cardiology, eResearch Technology Inc, Philadelphia, PA, USA 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. Keywords: tbo-filgrastim, electrocardiogram, QT interval, granulocyte colony-stimulating factor |
| Databáze: | OpenAIRE |
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