Online Program Home
My Program

Abstract Details

Activity Number: 315 - SPEED: Biopharmaceutical Applications: Trials, Biomarkers, and Enpoint Validation
Type: Contributed
Date/Time: Tuesday, July 31, 2018 : 9:25 AM to 10:10 AM
Sponsor: Biopharmaceutical Section
Abstract #332701
Title: Pre-Specified Bias Evaluation of ECG Measurements for Assay Sensitivity Assessment
Author(s): Xiaoli Hou* and Nancy Kim and Wei Gao and Leticia Arrington and Kajal Larson
Companies: Merck and Merck and Merck and Merck and Merck
Keywords: Concentration-response model; ECG measurement; Thorough QT (TQT); QTc; Positive control

During the recent development of a new molecular entity, the originally proposed clinically efficacious dose was increased to a higher dose to obtain potentially greater efficacy for this compound. Prior to this update, a dedicated thorough QT (TQT) trial had already demonstrated lack of QTc prolongation at a supratherapeutic dose achieving ~4 fold exposure to the original dose. Subsequently, a drug-drug interaction (DDI) study using the higher clinical dose was being planned, which was expected to provide a ~2-fold exposure margin to the higher proposed clinical dose and an opportunity to collect rich ECG data at higher exposures to augment the information across the program. Could an exposure-response analysis using the combination of the existing TQT data and the new QT data collected from this DDI study provide sufficient information to derisk QTc prolongation? Without a positive control for assay sensitivity, is it possible to increase confidence in the QT data collected from this DDI study? Will the regulatory agency accept this modeling approach without requiring a further dedicated TQT study? This talk will discuss these questions through a real life project.

Authors who are presenting talks have a * after their name.

Back to the full JSM 2018 program