Cardiovascular Safety Pharmacology: Best Practice Considerations for the In Vivo QTc Core Assay

The cardiovascular system is one of the three core battery vital functions which should be examined during safety pharmacology studies. The goal of cardiovascular safety pharmacology is to evaluate the effects of test substances on the most relevant parts of the cardiovascular system, in order to detect potentially undesirable effects, before engaging in clinical trials.

ICH guidelines provide information regarding best practices when designing and executing preclinical safety pharmacology studies. The in vivo QTc assay is used by the pharmaceutical industry to characterize the potential for delayed ventricular repolarization and is a core safety assay mentioned in ICH S7B guideline.

The first segment of this webinar will focus on the specific components in the ICH guidelines and how to incorporate them into an IND-enabling cardiovascular telemetry study design. The featured speakers will also discuss validation and verification procedures involved with establishing telemetry models in the preclinical setting.

In the second segment of this webinar, they will discuss exposure-response (ER) analysis, or pharmacokinetic/pharmacodynamic (PK/PD) analysis of cardiovascular telemetry data. While telemetry studies often make use of a crossover design that incorporates a dose-response analysis of QTc intervals over time, this does not take PK data into account.

Concentration QTc (C-QTc) analysis has been proposed as a valid alternative to the conventional approach which combines PK exposure and PD response data. In this segment, the speakers will also discuss power analysis (detection sensitivity) and its role in assessing study quality. They will review a case study where ER and power analysis were incorporated into a canine cardiovascular telemetry study after administration of dofetilide, an anti-arrhythmic known to cause QT prolongation.

Register for this webinar to understand how the in vivo QTc assay fits within the ICH guidelines, and learn how CV safety pharmacology study models are validated and verified.

Speakers

Ty Speece, BS, Safety Pharmacology, Inotiv

Ty Speece joined the Safety Pharmacology team at Inotiv in September 2020 bringing over 15 years of experience to the company. His expertise working with cardiovascular telemetry models has allowed Inotiv to accelerate the growth of its safety pharmacology center of excellence and represents an important milestone in the company’s progression.

Before becoming part of the Inotiv team, Ty held roles of increasing responsibility, leading teams and supporting nonclinical research, at multiple contract research organizations. His preclinical background comes from GLP and non-GLP safety pharmacology as well as toxicology, efficacy, discovery and DMPK studies across multiple species. In his study director role, he is responsible for the scientific integrity of studies, developing novel models, ensuring confirmation with all applicable regulatory guidelines, and preparing detailed study reports to support IND submissions.

Ty earned his BS in Biology from Emporia State University. He has been a member of the Safety Pharmacology Society for 14 years and has contributed to more than 10 scientific research publications and presentations.

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Joel Baublits, MS, Director of Operations, Cardiovascular Analytics

Joel Baublits joined Cardiovascular Analytics, LLC, in July 2019 as the Director of Operations overseeing Safety Pharmacology and Toxicology. Here, he holds multiple roles, including working with clients to develop analysis strategies in support of GLP and non-GLP studies.

Before joining Cardiovascular Analytics, Joel provided scientific contributions across various areas, including safety pharmacology, efficacy, toxicology, and in vivo lead model development. He also has the responsibility of scientific oversight for studies in disease models such as heart failure, hypertension, and stroke.

Joel earned his MS in Biomedical Science and his BS in Biology from Kansas State University. He has contributed to the scientific community with multiple posters, peer-reviewed publications, and public presentations. Joel is a member of the Safety Pharmacology Society and the American College of Toxicology.

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