Exposure-Response Modeling Approach for Assessing QT Effect in 'Thorough' QT/QTc Studies
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*Balakrishna Sadashiv Hosmane, Northern Illinois University 

Keywords: QT Interval, thorough QT/QTc study, Exposure-Response Modeling

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 (e.g., terfenadine and cisapride) or the placement of restrictions on their use (e.g., ziprasidone and ranolizine). The delay of cardiac repolarization is defined as the QT interval and is measured using the patient’s electrocardiogram (ECG).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. This approach to the assessment of non-inferiority of the higher dose to placebo is one of the alternative strategies suggested in ICH-E14 guideline to the intersection