Can Pooled SAD/MAD Studies Give Early Indication of Possible QTc Signal?

• Activity Number: 67
• Type: Topic Contributed
• Date/Time: Sunday, August 4, 2013 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kimberly Crimin*+
• Companies: Novartis Pharmaceutical Corporation
• Keywords: QTc ; SAD/MAD ; TQT

Abstract

The ICH E14 guidance indicates the concentration response relationship for QTc prolongation should be characterized. This evaluation is typically done in a TQT study, which for most programs is not conduct early in the development program. PK and ECG data is regularly collected in early studies, such as SAD/MAD. This leads to the question, are we doing enough with our early data? In this talk the statistical model for analyzing QTc data collected in SAD/MAD studies is provided. An example is shown which uses the proposed methodology to analyze pooled SAD/MAD data and the results of the TQT study presented. Simulation results are provided which can give guidance as to when early studies may be helpful in identifying an early signal.