Enabling Robust PK/QTc Assessment in Single and Multiple Ascending Dose Trials for Evaluation of QTc Prolongation

• Activity Number: 254
• Type: Contributed
• Date/Time: Monday, August 1, 2016 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Fang Liu* and Li Fan and Kuenhi Tsai and Devan V. Mehrotra
• Companies: Merck and Merck and Merck and Merck
• Keywords: Concentration-response ; SAD ; MAD ; QTc

Abstract

Thorough QT (TQT) studies are considered as expensive and their corresponding statistical analysis methodology, based on the ICH E14 guidance, has been criticized as too conservative in some publications. The ICH E14 Q&A (R3), released in December, 2015, states that concentration-response analysis with all available data across all doses to characterize the potential for a drug to influence QTc, can serve as an alternative for decisions to classify the risk of a drug. This presentation will investigate how well the drug concentration effect on QTc prolongation in various concentration-response models can be captured after combining single ascending dose (SAD) studies and multiple ascending dose (MAD) studies.