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Investigational New Drugs
Published in: Investigational New Drugs 5/2013

01-10-2013 | PHASE II STUDIES

Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study

Authors: Tim Eisen, Yaroslav Shparyk, Nicholas Macleod, Robert Jones, Gudrun Wallenstein, Graham Temple, Yasser Khder, Claudia Dallinger, Matus Studeny, Arsene-Bienvenu Loembe, Igor Bondarenko

Published in: Investigational New Drugs | Issue 5/2013

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Summary

Purpose Some targeted anticancer agents are associated with serious ventricular tachyarrhythmias, which may be predicted by electrocardiographic evaluation of drug-related QT prolongation. We studied the effects of nintedanib (BIBF 1120; an oral, triple angiokinase inhibitor targeting vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors) on the QT interval in patients with renal cell carcinoma (RCC) participating in an open-label phase II trial. Methods Treatment-naïve, adult patients with unresectable/metastatic, clear cell RCC received nintedanib 200 mg twice daily. QT intervals were evaluated at baseline (day −1), on day 1 (after the first dose), and on day 15 (steady state) by 12-lead electrocardiograms (ECGs) performed in triplicate. Pharmacokinetic sampling was also undertaken. Results Among 64 evaluable patients, the upper limits of the 2-sided 90 % confidence intervals for the adjusted mean time-matched changes in QTcF interval (corrected for heart rate by Fridericia’s method) from baseline to day 1 and 15 (primary ECG endpoint) were well below the regulatory threshold of 10 ms at all times. No relationship between nintedanib exposure and change from baseline in QTcF was seen. Nintedanib was generally well tolerated with no drug-related cardiovascular adverse events. Conclusion Nintedanib administered at 200 mg twice daily was not associated with clinically relevant QT prolongation.
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Metadata
Title
Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study
Authors
Tim Eisen
Yaroslav Shparyk
Nicholas Macleod
Robert Jones
Gudrun Wallenstein
Graham Temple
Yasser Khder
Claudia Dallinger
Matus Studeny
Arsene-Bienvenu Loembe
Igor Bondarenko
Publication date
01-10-2013
Publisher
Springer US
Published in
Investigational New Drugs / Issue 5/2013
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-013-9962-7

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