Beyond the Linear Model: Fully Automated Concentration-QT Analysis and Reporting

Authors: Cellière G, Krause A, Bonnefois G, Chauvin J
Conference: PAGE
Keywords: concentration-QT analysis, drug development, linear mixed-effects model., MonolixSuite
Software: Monolix®
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • QT interval prolongation assessment as a marker for risk of drug-induced arrythmia is an integral part of drug development for small molecules.
  • QT analysis may be carried out with concentration-QTc modeling based on entry-into- man (SAD and MAD studies) as an alternative to thorough QT (TQT) studies [1].
  • The scientific white paper (Garnett et al. [2]) provides guidance for performing and reporting concentration-QT modeling to support regulatory submissions.
  • The standard model is a linear mixed-effects model.

By Géraldine Cellière, Andreas Krause, Guillaume Bonnefois, Jonathan Chauvin

PAGE 2025, Thessaloniki, Greece, June 3-6, 2025