EARLY CARDIAC SAFETY ASSESSMENT

An Earlier Look at QT Prolongation

In December 2014, the news of a technique for assessing QT/QTc from data captured during Clinical Pharmacology 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 QT prolongation assessment as early as a First-In-Human trial. The method, early precision QT, collects up to 100 ECGs per timepoint using greatly improved algorithms that are paired with the pharmacokinetic data to generate a concentration-response curve. This results in a very robust data set which can be submitted to the FDA to receive a potential waiver for a thorough QT prolongation (TQT) study.

Experience the Difference

Altasciences is well positioned to support the classic thorough QT studies or the new early precision QT studies. The expertise of the technical staff at our state-of-the-art clinical pharmacology campuses is key for the successful completion of these complex cardiac safety studies.

We have 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.

Development Advantages

• 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)
• Ability to 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

Methodology Advantages

• High Precision QT analysis, combined with concentration/effect modeling, increases the power allowing the precision to see small QT changes
• 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 and Holter Evaluation

• Traditional ECG monitoring
• High Precision QT for interval evaluation
• Industry-validated Dynamic QT beat-to-beat approach for early QT assessments performed in traditional Phase I studies