A drug’s propensity to cause QT prolongation has to be carefully evaluated in the course of clinical development, and until recently, regulators have required a designated study, the thorough QT (TQT) study, to rule out a small QT effect. It has however become increasingly clear that the TQT study is overly sensitive and results in a number of false positives, i.e. drugs that are labelled as causing clinically relevant QT prolongation based on a very small effect, which is unlikely to be proarrhythmic.
Exposure response analysis has emerged as an important way to predict drug-induced QT effects in patients and have been widely applied to data from TQT studies. More recently, a collaborative initiative was undertaken between industry, the Cardiac Safety Research Consortium and FDA, to prospectively evaluate whether exposure response analysis applied to data from early clinical trials using intense ECG monitoring with a High Precision QT technique can detect the QT effect of a group of known QT prolonging drugs. The objective was to demonstrate that this approach can exclude small QT effects with the same confidence as in TQT studies and thereby serve as a replacement. The IQ-CSRC study was fully successful and has led to the decision by the ICH E14 group to revise the clinical guidance document.
The purpose of this webinar is to share the results of the IQ-CSRC study, discuss best practices for collection of high precision ECG data at the site, discuss what it will take to obtain a waiver for the TQT study and to which extent there is a remaining role for TQT studies.
Hear from Dr. Borje Darpo, CSO, iCardiac and Dr. Emanuel DeNoia, Medical Director at ICON, a Certified and Preferred Site in iCardiac’s Early Precision QT program.
Dr. Borje Darpo, Chief Scientific Officer, iCardiac Technologies
Borje Darpo is board-certified in cardiology and internal medicine and Associate Professor of Cardiology at the Karolinska Institute since 2000. He has 18 years of industry experience, including senior management positions in small, mid-sized, and large pharma, as well as from a global CRO. He has led or has been responsible for projects in all phases of clinical development, including filing and approval of an NDA. Dr. Darpo’s experience from cardiovascular safety assessment of drugs is broad and includes participation in the generation of existent regulatory guidance on QT assessment (CHMP and ICH E14), previous co-chair of the ILSI/HESI cardiovascular safety subcommittee, previous co-chair of the scientific oversight committee of CSRC, generation of internal company-specific guidance on cardiovascular safety assessment, and numerous reviews of programs both internally and as a consultant. Dr. Darpo has served as the EFPIA deputy topic leader for the ICH E14 Implementation Working Group, which worked with implementation of this guidance and support to Sponsors through a Q&A process. Dr. Darpo is a member of the Scientific Oversight Committee for the Cardiac Safety Research Consortium (CSRC) with participation from FDA, academia, and EU/US industry. Dr. Darpo has co-authored numerous publications on QT assessment, including White Papers on ‘Early QT assessment’ and the IQ-CSRC study validating ECG evaluation in early stage clinical studies.
Dr. Emanuel DeNoia, Medical Director, ICON Early Phase Services
Dr. Emanuel DeNoia received his Doctor of Medicine in 1975 from the College of Medicine of New Jersey. After training in internal medicine and medical residency at Monmouth Medical Center, he opened his practice in Internal Medicine and served on numerous boards and committees, including a term as the Chairmen of the Department of Medicine at Humana Hospital San Antonio. He joined Healthcare Discoveries in 1995 as a Clinical Investigator in Phase I and has been a full time investigator with the ICON since 2005. Dr. DeNoia has acted as Principal Investigator or Sub-Investigator for over 100 studies and is actively involved in the training of staff for ECG collection during TQT and Early Precision QT studies completed in collaboration with iCardiac to help ensure high precision ECG data collection.
Who Should Attend?
CEO, Chief Medical Officer, Chief Scientific Officer and other senior level executives involved in Early Clinical Development, R&D, Regulatory, and Clinical Operations for Bio/Pharmaceutical companies. This presentation will especially benefit those working in Phase I, Phase II or cardiac safety.
ICON specialises in the strategic development, management and analysis of programs that support clinical development, from compound selection to Phase I-IV clinical studies. ICON’s San Antonio clinical research unit (CRU) is a certified and preferred site in iCardiac’s Early Precision QT program, based on specialized training, its Mortara Surveyor ECG system, and its consistent delivery of high precision ECG data over multiple studies.
iCardiac Technologies, Inc. is a leading global provider of high precision, centralized cardiac safety and respiratory services supporting the Pharmaceutical industry. Its team of medical and scientific experts has over 100 years of combined cardiology, pulmonary, drug development, and regulatory expertise. iCardiac team members seek to advance the field of cardiac safety pulmonary function evaluation in clinical research. Its scientific leadership serves as key contributor to several FDA working groups.