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Nov 10, 2020
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Implementation of the C-QTc study using MonolixSuite applications

Introduction

International Council for Harmonisation (ICH) E14 guidance agreed to use a model-based study of concentration-QT data as a primary analysis in the proarrhythmic risk assessment

Modelling guidelines: pre-specified LME model presented in “Scientific white paper on concentration-QTc modelling” by Ch.
Garnett et al. ( J. Pharmacokinet. Phar. 2017)

  • Check the model assumption via exploratory plots
  • Develop the relationship between a drug concentration and the change from baseline of the heart rate corrected QT interval
    corrected by placebo (ΔΔQTc)
  • Compute the mean ΔΔQTc at concentration of interest and 90% double sided confidence interval
  • Assess if the QTc prolongation exceeds the 10ms regulatory threshold

Presented at ACoP 11 Virtual Conference, Nov. 9-13, 2020

By Monika Twarogowska, Géraldine Ayral, Jonathan Chauvin, Pauline Traynard

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