435 – Clinical Trial Design III
Evaluation of QT Correction Methods and Gender Effect on QTc Intervals Following Moxifloxacin Administration
Bhavna Solanki
Janssen R&D
Jaya Natarajan
Janssen R&D
ICH E14 requires a Thorough QT(TQT) study for most new compounds to assess for the potential to prolong QT/QTc intervals, which is associated with Torsade de Points (TdP). Females have longer QT intervals. TQT studies are conducted with two doses of the investigational drug, placebo and a positive control to assess assay sensitivity. Moxifloxacin 400 mg is the most commonly used positive control in TQT studies. Usually, several methods (Bazett, Friderica and study-specific) for correcting the QT intervals for heart rate (QTc) are used in the evaluation. In this work, we evaluate the relationship between QTc interval data (corrected for heart rate for different methods including Fridericia, Bazett and study specific) and RR using both pre dose and post dose data from placebo and moxifloxacin administration in several TQT studies conducted by Janssen R&D, to evaluate the selection of a primary correction method. We will also evaluate the gender effect on moxifloxacin response.