The IQ-CSRC prospective clinical Phase 1 study: “Can early QT assessment using exposure response analysis replace the thorough QT study?”

A collaboration between the Consortium for Innovation and Quality in Pharmaceutical Development and the Cardiac Safety Research Consortium has been formed to design a clinical study in healthy subjects demonstrating that the thorough QT (TQT) study can be replaced by robust ECG monitoring and exposure-response (ER) analysis of data generated from First-in-Man single ascending dose […]

Read More
Topics:

Impact of Electrocardiographic Data Quality on Moxifloxacin Response in Thorough QT/QTc Studies.

Thorough QT studies are typically conducted for drugs with systemic bioavailability and include a positive control, typically moxifloxacin, with a well-described QTc effect. This study tested two hypotheses: that (i) re-measuring the QT intervals based on electrocardiogram (ECG) pattern similarity improves the moxifloxacin time profile, and (ii) that study conduct influences the ability to detect […]

Read More
Topics:

Improving the Assessment of Heart Toxicity for All New Drugs Through Translational Regulatory Science

Fourteen drugs have been removed from the market worldwide because they cause torsade de pointes. Most drugs that cause torsade can be identified by assessing whether they block the human ether à gogo related gene (hERG) potassium channel and prolong the QT interval on the electrocardiogram. In response, regulatory agencies require new drugs to undergo […]

Read More
Topics:

Cardiac safety research consortium: Can the thorough QT/QTc study be replaced by early QT assessment in routine clinical pharmacology studies? Scientific update and a research proposal for a path forward

The International Conference on Harmonization E14 guidance for the clinical evaluation of QT/QTc interval prolongation requires almost all new drugs to undergo a dedicated clinical study, primarily in healthy volunteers, the so-called TQT study. Since 2005, when the E14 guidance was implemented in United States and Europe, close to 400 TQT studies have been conducted. […]

Read More
Topics:

A Change of Heart at the Cardiac Safety Research Consortium

Christine Garnett

The ICH E14 guidance recommends that all new drugs with systemic bioavailability are assessed for the ability to delay cardiac repolarization as measured by the QT/QTc interval on the surface ECG. For most drugs, this evaluation is performed in the Thorough QT/QTc (TQT) study. Could using model-based approaches during routine early studies influence the current […]

Read More
Topics: Drug Safety, PK/PD Modeling and Simulation
Learn More
LinkedIn