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Design, Conduct and Analysis of Thorough QT Studies

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Abstract

Torsades de Pointes (TdP) is a type of polymorphic ventricular tachycardia that can result in fainting and death. While there are genetic causes for TdP, such as ion channel mutations, drug-induced TdP can occur, an event that first gained prominence with the interaction between terfenadine and ketoconazole. While TdP itself cannot be studied in clinical trials due to its low rate of incidence, a biomarker for TdP is prolongation of the QT interval on an ECG. Today, almost every drug is expected to be evaluated for its potential to prolong QT interval. This chapter discusses measurement of QT intervals in clinical trials, the design and analysis of “thorough” QT studies, including the intersection–union test and concentration-QT modeling, as well as practical matters related to the International Conference on Harmonisation’s E14 guidance.

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Acknowledgements

Thank you to Steve Riley for his consultation on Sect. 10.6.2.

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Authors and Affiliations

  1. Oncology Clinical Pharmacology, Pfizer, 10646 Science Center Drive (CB10/2503), San Diego, CA, 92121, USA

    Tanya Russell

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  1. Tanya Russell
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  2. Daniel S. Stein
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  3. David J. Kazierad
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Correspondence to Tanya Russell .

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Editors and Affiliations

  1. , Pharmacokinetics, Modeling, and Simulati, Astellas Pharma, Parkway North 3, Deerfield, 60015, Illinois, USA

    Peter L. Bonate

  2. Institutes for Biomedical Research, Translational Sciences, Novartis, Health Plaza 1, East Hanover, 07936, New Jersey, USA

    Danny R. Howard

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© 2011 American Association of Pharmaceutical Scientists

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Russell, T., Stein, D.S., Kazierad, D.J. (2011). Design, Conduct and Analysis of Thorough QT Studies. In: Bonate, P., Howard, D. (eds) Pharmacokinetics in Drug Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7937-7_10

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