Exposure-Response Modeling Approach for Assessing QT Effect in 'Thorough' QT/QTc Studies

• Activity Number: 62
• Type: Topic Contributed
• Date/Time: Sunday, August 1, 2010 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Balakrishna Sadashiv Hosmane*+ and Charles Locke and Yi-Lin Chiu
• Companies: Northern Illinois University and Abbott Laboratories and Abbott Global Pharmaceuticals Research and Development
• Keywords: QT Interval ; Thorough QT/QTc study ; ECG

Abstract

A potential problem with some drugs is their ability to delay cardiac repolarization, a condition that may trigger a cardiac arrest. Over the past decade, these cardiac adverse events have resulted in a number of patient deaths and either the subsequent removal from the market of previously approved drugs or the placement of restrictions on their use. The delay of cardiac repolarization is defined as the QT interval and is measured using the patient's electrocardiogram (ECG). Drugs are expected to receive a clinical ECG evaluation, as mandated by the International Conference on Harmonization (ICH E14) guidance. We assess the QT effect using an exposure-response model in a 'thorough QT/QTc study' with a four-period crossover design in which the treatments are placebo, positive control, higher dose of investigational drug, and therapeutic dose of investigational drug.