Integration of ICH E14 Cardiac safety in First Time in Man and other Phase I healthy volunteer studies - Opportunities and Challenges

Abstract

Event Abstract Back to Event Integration of ICH E14 Cardiac safety in First Time in Man and other Phase I healthy volunteer studies - Opportunities and Challenges Jörg Täubel1, 2*, Sara Fernandes1 and Georg Ferber3 1 Richmond Pharmacology Ltd., UK 2 St George's University of London, Cardiovascular and Cell Sciences Research Institute, UK 3 Statistik Georg Ferber GmbH, Switzerland Background: The current FDA thinking manifested on the most recent Q&A document accepts the use of ECG data collected from Phase I studies in conjunction with concentration-effect modelling to assess arrhythmogenic risk. The need to show assay sensitivity is currently a major obstacle if a clinically relevant effect is to be excluded when supratherapeutic plasma concentrations cannot be achieved. Methods: ECG and Holter data from different Thorough QT and Phase I studies were used. Standardised meals were served in all studies. Concentration-effect analyses based on QTc interval were performed. Sensitivity was confirmed by demonstrating a significant shortening of QTcF after a standardised meal. Simulation work was used to assess stability and the power of effect after start of the meal. Results: Case studies will be presented to demonstrate that time-effect attributed to food is stable and meal-induced changes on QTc are reproducible with a power greater than 80%. Intrasubject variability of the response suggests that this approach can perform as well as moxifloxacin as the number of subjects showing QT-prolongation after food is comparable to the number of QT-shortening cases with moxifloxacin. Conclusions: This presentation describes what aspects and key design features can enhance the power of the analysis and how increased efficiency can be attained in Phase I studies. Points to be considered in data analysis when determining assay sensitivity will be detailed. The results on stability and the power of effect support the effective integration of the food effect on QTc in a study to establish assay sensitivity. Keywords: Risk Management, patient recruitment, Exploratory clinical trials, human pharmacology, early phase drug development, over-volunteering Conference: EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017. Presentation Type: Poster Topic: EUFEMED 2017 CONFERENCE Citation: Täubel J, Fernandes S and Ferber G (2019). Integration of ICH E14 Cardiac safety in First Time in Man and other Phase I healthy volunteer studies - Opportunities and Challenges. Front. Pharmacol. Conference Abstract: EUFEMED 2017. doi: 10.3389/conf.fphar.2017.62.00009 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Aug 2017; Published Online: 25 Jan 2019. * Correspondence: Dr. Jörg Täubel, Richmond Pharmacology Ltd., London, UK, j.taubel@richmondpharmacology.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jörg Täubel Sara Fernandes Georg Ferber Google Jörg Täubel Sara Fernandes Georg Ferber Google Scholar Jörg Täubel Sara Fernandes Georg Ferber PubMed Jörg Täubel Sara Fernandes Georg Ferber Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.