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Matters of the heart
DUBLIN—In an effort targeted toward ensuring the cardiac safety of new drugs earlier and more precisely than ever, Ireland-based ICON plc, a global provider of drug development services to the pharmaceutical, biotechnology and medical devices industries, has announced that its San Antonio-based research arm is a certified and preferred site in the Early Precision QT program of Rochester, N.Y.-based iCardiac Technologies.
ICON announced Nov. 3 that the San Antonio site will test the cardiac safety of new compounds in Phase 1 clinical trials rather than wait until Phase 2 or Phase 3, thus potentially eliminating the need for a separate thorough QT (TQT) study in later stages of development.
The savings could be quite significant, with marginal costs in a single ascending dose (SAD) or multiple ascending dose (MAD) Phase 1 study ranging from $150,000 to $200,000, compared to a later traditional TQT study costing as much as $2 million to $5 million, according to ICON.
The U.S. Food and Drug Administration (FDA) has since 2005 required all new compounds in development to be tested for cardiac safety. A dedicated TQT study determines the compound’s impact on the QT interval—the time between the start of the Q wave and the end of the T wave during the heart’s electrical cycle. A prolonged QT interval indicates a potential safety risk for a new drug.
TQT studies typically occur with Phase 2 or 3 trials; however, the results of a prospective validation study carried out in December 2014 through a collaboration between the FDA and the Cardiac Safety Research Consortium, demonstrated that actionable cardiac safety assessments can be conducted in Phase 1 trials using electrocardiograms (ECGs) collected during routine SAD (single ascending dose) or MAD (multiple ascending dose) studies.
“We are looking to streamline the time and cost of early clinical development through our industry-leading technologies, agile and adaptive processes and by collaborating with industry partners who can bring new approaches to drug development,” according to Steve Unwin, executive vice president for ICON’s Early Phase Services division.
Unwin tells DDNews, “As an iCardiac Certified Site Partner, we can help our clients to assess the cardiac safety of their compounds earlier and more precisely, which will enable them to prioritize clinical programs with strong safety profiles.”
On the differences between SAD and MAD studies, Unwin explains that in SAD studies, small groups of subjects are given a single dose of the proposed drug while they are observed and tested for a period of time to confirm safety.
“Typically, a small number of participants, usually three, are entered sequentially at a particular dose,” Unwin said. “If they do not exhibit any adverse side effects, and the pharmacokinetic data are roughly in line with predicted safe values, the dose is escalated and a new group of subjects is then given a higher dose.”
MAD trials “investigate the pharmacokinetics and pharmacodynamics of multiple doses of the drug, looking at safety and tolerability,” Unwin said. “In these studies, a group of patients receives multiple low doses of the drug, while samples (of blood and other fluids) are collected at various time points and analyzed to acquire information on how the drug is processed within the body. The dose is subsequently escalated for further groups, up to a predetermined level.”
ICON and iCardiac have collaborated on 12 studies over the past seven years involving cardiac monitoring, acquisition of ECG wave forms and intensive analysis of ECGs, he said.
Other regulatory agencies outside of the United States are evaluating whether to adopt this new approach to evaluating QT intervals, Unwin adds. This could lead to more demand for iCardiac Early Precision QT services.
“However, an interesting point to note is that in September 2015, the FDA granted the first TQT study waiver, which was based on data from an iCardiac Early Precision QT study conducted during Phase 1 and first-in-human studies,” Unwin says.
Alex Zapesochny, president and CEO of iCardiac Technologies, stated, “ICON and iCardiac have frequently worked together on QT assessment studies, and that working experience has repeatedly confirmed the strong expertise that ICON possesses in ensuring that cardiac safety data of the highest quality is acquired during their Phase 1 studies. We look forward to continuing to work closely with ICON to bring the many benefits of Early Precision QT to their clients.”
iCardiac serves seven of the top 10 global pharma, as well as numerous small and mid-sized pharma and biotech companies. iCardiac team members are active contributors on several FDA working groups that are advancing the field of cardiac safety.
ICON specializes in the strategic development, management and analysis of programs that support clinical development from compound selection to Phase 1-4 clinical studies. ICON operates from 77 locations in 38 countries and has approximately 11,700 employees.