An Earlier Look at QT Prolongation
In December 2014, the news of a technique for assessing QT/QTc from data captured during Phase I clinical trials was shared during the FDA-hosted Cardiac Safety Research Consortium (CSRC) meeting.
The study by the FDA and CSRC demonstrated that new cardiac technology allows for assessment as early as a First-In-Human trial. The methodology includes a significant increase in ECG data evaluation, use of improved algorithms for cardiac assessment and careful analysis of compound systemic exposure to create a powerful combination of maximal data points in a smaller clinical trial performed as part of a required early stage study.
- Early QT safety assessment of drug candidates
- Confirmation of preclinical cardiovascular safety findings for more informed development decisions and/or potentially “save” drugs that have tested positive in non-conclusive preclinical screening methods (i.e. Purkinje Fiber, ion channel and HERG assays)
- De-risk drug candidates by providing a more precise indicator of arrhythmia liability prior to late stage development investment
- Improved development package for licensing or further in-house development
- Considerable time and cost savings if TQT waiver can be obtained
Experience the Difference
Vince & Associates Clinical Research is well positioned to support the current and potentially shifting guidance expected next year. The expertise of the technical staff at our state-of-the-art clinical pharmacology campus is key for the successful completion of these complex cardiac safety studies.
Expert Staff: Vince & Associates has full-time research physicians focused solely on clinical research, trained nurse researchers, 24/7 paramedic coverage and new facilities purpose built for early phase clinical trials.
CSRC Member: Vince & Associates is a member of the Cardiac Safety Research Consortium (CSRC) and participates with industry leaders on key issues that impact cardiac safety, including alternative approaches to ICH E14 for the assessment of arrhythmia liability in early drug development.
- High Precision QT analysis combined with concentration/effect modeling overcomes the limited semi-automated ECG reading approaches that cannot exclude minor QT effect and insufficient power to overcome variability due to low precision
- High Precision QT analysis allows for TQT-like statistical power in smaller studies such as Single and Multiple Ascending Dose (SAD/MAD) trials
- Potential elimination of the traditional TQT study for some drugs if the early trial is scientifically rigorous and adequately designed; provides preparatory information for cases where the TQT study will need to be completed.
ECG & Holter Evaluation
- Traditional ECG monitoring
- High-Precision QT for interval evaluation
- Industry-validated Dynamic QT beat-to-beat approach for early QT studies performed in traditional Phase I studies