Characterization of the Heart Rate, QT Interval and Appropriate QTc of Conscious Beagle Dogs, Chair-trained Monkeys and Anesthetized Mongrel Dogs in Telemetry Studies

• Activity Number: 318
• Type: Invited
• Date/Time: Wednesday, August 11, 2004 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Lori Mixson*+ and Chao-Min L. Hoe and Hugo Vargas and Peter Siegl and Richard Briscoe
• Companies: Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc.
• Keywords: telemetry ; preclinical ; simulation

Abstract

Understanding, interpreting, and predicting QT prolongation caused by drug treatment is important for health outcomes, as there is a risk for sudden death. As such, there is also an increased regulatory interest in detecting potential QT prolonging drugs early in development. New statistical methods arise from improved technology to measure cardiac function. Telemetry studies in animals are key to the safety assessment of research compounds. Electrocardiography (ECG) data from telemetry studies conducted on conscious beagles (14 studies), chair-trained monkeys (10 studies), and anesthetized mongrel dogs (14 studies) were analyzed to characterize the heart rate and QT interval. This data consisted of approximately 20 hours of pre-dosing/baseline measurements collected at one-minute intervals. Each study was a 4 X 4 cross-over design, such that each animal in a study contributed 1,200 minutes per time period to the analysis. The variation over time within animal and variation among animals was used to calculate the variation in the strength of the association between heart rate and QT.