A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Bruce A HugDaryl Sonnichsen

Abstract

Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were </=10 milliseconds greater than the co...Continue Reading

References

May 9, 2000·Clinical Pharmacology and Therapeutics·R E BentonR L Woosley
Sep 5, 2002·British Journal of Clinical Pharmacology·Rashmi R Shah
Jul 30, 2005·Cancer Letters·Sridhar K Rabindran
May 19, 2006·Journal of Clinical Pharmacology·Borje DarpoDiane K Jorkasky
Nov 21, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Giuseppe CuriglianoRashmi Shah
Jun 6, 2008·Mayo Clinic Proceedings·Edith A PerezMichael S Ewer
Mar 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kwok-K WongHoward A Burris
Nov 6, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pamela N MunsterMarian Iwamoto
Nov 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carlo L BelloLee Rosen
Feb 10, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Harold J BursteinRajendra Badwe

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Citations

Sep 13, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A AwadaE Staroslawska
Jul 7, 2012·Future Oncology·Sara López-TarruellaMiguel Martín
Jun 11, 2016·Expert Opinion on Drug Metabolism & Toxicology·Hampig Raphael KourieAhmad Awada
Oct 4, 2016·Expert Opinion on Pharmacotherapy·Annemie Prové, Luc Dirix
Nov 2, 2019·Clinical and Translational Science·Mariam A AhmedDaria Stypinski
Sep 9, 2017·Drugs·Emma D Deeks
Oct 31, 2017·Cancer Chemotherapy and Pharmacology·Jan de JongDaniele Ouellet

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