Abstract
In December 2015, the International Conference of Harmonization (ICH) E14 guideline generated guidance on how exposure-response modelling can be used to characterise the potential for a drug to affect cardiac repolarisation and to modulate the QTc interval. The released Q&A document describes how data from Phase I ascending dose SAD and MAD studies can be used in the right circumstances to be accepted by regulatory bodies as an alternative approach to TQT to demonstrate cardiac safety. While this strategy is now being expanded to all new drugs, this alternative analysis has been extensively used in the past. This commentary discusses the results of a retrospective analysis where a concentration-effect analysis validated by meal effects on the ECG was applied to a Phase I study to investigate the PK, PD and safety of escalating single doses of a highly selective sigma1 receptor antagonist.
Highlights
The adoption in May 2005 of the International Conference of Harmonization (ICH) E14 guideline established recommendations on the strategy for the clinical evaluation of the propensity of new drugs to cause QTc prolongation [1]
The most recent Q&A document gives the option of using either Phase I ECG data or data from a TQT study to characterise the potential for a drug to influence QTc as long as high quality ECG recording and analysis are performed [2]
For a study to be considered negative the upper bound of the two-sided 90% confidence interval for the QTc effect of a drug treatment as estimated by exposure-response analysis should be
Summary
The Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity in Phase I Studies.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
