Drug-induced cardiovascular adverse events are one of the leading causes of drug withdrawals from the market and of drug label restrictions. As a result, it is essential to determine early in the R&D cycle whether new drug candidates have a propensity to cause arrhythmias.
While “thorough QT/QTc study (TQT)” has been required by the FDA since 2005, TQT studies are expensive and time-consuming. Certara’s Cardiac Safety Simulator (CSS) is a stand-alone, systems biology-driven, modeling and simulation-based platform for the assessment of the pro-arrhythmic potency of drugs, new chemical entities, and other xenobiotics within the targeted clinical population.
CSS allows you to make more informed go/no go decisions regarding your new drug candidates.
- Enable early assessment of cardiac liability:
Enhanced quantitative structure activity relationship (QSAR) models enable assessment of drug triggered ion channel current inhibition, even when in vitro data are not available
- Account for inhibition of multiple ion channels
- Comprehensive cardiac safety assessment: Use demographic, physiological, and genetic information to evaluate a drug’s risk of cardiac toxicity
- Evaluate various ECG related outputs/ endpoints such as QT/ QTc, QRS, J-Tpeak, and Tpeak-Tend
- Predict population variability and drug triggered physiology modifications
Early stage drug development
CSS can be used in as a screening tool, even in situations where no in vitro data are available. In pre-clinical development, it brings together QSAR and in vitro physiological measurements, generating early information on cardiac safety without incurring additional cost.
In vivo data can be combined with CSS to enable a more robust assessment of cardiac risk with a focus on the impact of population variability.
- Visualize and analyze simulation results
with a flexible, Excel®-based tool
- Evaluate up to 7 chemical species simultaneously (drugs, metabolites and other exogenous xenobiotics and endogenous substances) interacting at the ion channel(s) level
- Connect CSS to the Simcyp Simulator, the leading platform for population-based in vitro-in vivo (IVIVE)/ physiologically-based pharmacokinetics (PBPK). Combining knowledge gained from the Simcyp Simulator and CSS helps to facilitate the design of clinical studies.