CNS and Chronic Drug Trials: New Cardiac Safety Requirements
Drugs that are chronically administered, such as those for CNS disease states, are under increased scrutiny for potential effects on cardiac safety endpoints, and for good reason. Whereas a small change in blood pressure may be inconsequential for drugs administered over a short timeframe, the story is very different for drugs that are likely to be taken for years or decades. Prolonged changes in blood pressure or QT interval are associated with a variety of patient health risks and prescribers need to carefully weigh the risks and benefits. Regulatory agencies understand this challenge and have drafted recent guidance to better detect even small changes in cardiac safety, ensuring that a drug’s risk profile is well-established during development, with increased attention given to chronically administered drugs.
Further changes are coming to clinical trials, and drug developers need to be prepared to think about the cardiac safety of their drugs, beyond just QT/ECG evaluation. While blood pressure has long been a part of safety endpoints for select drugs with known risk, there has not been a formal guidance in place. In February of 2022, the US Food and Drug Administration (FDA) issued their draft Pressor Effect Guidance, with a particular focus on chronic-use drugs. The draft guidance also looked at common modalities for blood pressure collection, highlighting the advantages of Ambulatory Blood Pressure Monitoring (ABPM).
For long-term CNS drugs, blood pressure evaluation has become a critical consideration to establish the potential risk for stroke or other cardiovascular diseases. Blood pressure has also been implicated as a risk factor for neurological disease states as the brain is a frequent target of hypertension-induced damage. The link between blood pressure and brain pathology is mounting as studies have shown a correlation between blood pressure and CNS disorders such as dementia or Alzheimer’s, and a number of high-profile CNS drugs have been shown to have a significant impact on blood pressure.
Join featured experts from Clario as they discuss the cardiac safety requirements (BP & ECG) for CNS and chronically administered drugs. The speakers will then take a closer look at the regulatory, scientific and technological evolutions in blood pressure and how these have impacted clinical trial design. The strengths and challenges of blood pressure modalities will be assessed for various study types, with a focus on ABPM per the draft guidance.
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Speakers
Dr. Robert Kleiman, M.D.
Vice President & Chief Medical Officer, Cardiology at Clario
Dr. Robert Kleiman is the VP & Chief Medical Officer for Cardiology at Clario, with board certifications in cardiology and cardiac electrophysiology. He has performed research in both basic cellular electrophysiology as well as clinical electrophysiology. Dr. Kleiman trained at the University of Pennsylvania and practiced clinical cardiology for 12 years before joining Clario in 2003.
In his current role, he currently oversees all of Clario’s cardiology services, supports business development and provides cardiac safety consultative services advising sponsors on optimal cardiac safety strategy for their development program (e.g. clinical protocol development, expert cardiac report development and regulatory support).
Jeff Heilbraun, MS
Vice President, Medical And Scientific Affairs, Cardiology at Clario
Jeff Heilbraun is the Vice President of Medical and Scientific Affairs, Cardiac Safety at Clario. He completed his Bachelor of Science degree in Biology at Tufts University in Boston with a focus on physiology and his Master of Science in Health Promotion and Disease Management studies at the American University in Washington DC where he continued as an adjunct professor in the Health Promotion program. Throughout his career, Jeff has maintained his focus on the science, technology, trial design and regulatory considerations surrounding cardiac safety (ECG and blood pressure endpoints) within pharmaceutical development, with a special interest in haemodynamics.
In his current role, he supports business development, provides cardiac safety consultative services advising sponsors on optimal cardiac safety strategy for their development program (e.g. clinical protocol development and regulatory support), and supports both project and cardiac product management teams.