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Session: Poster session II
Session starts: Thursday 24 January, 16:00

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Hein van der Wall (Centre for Human Drug Research)
Pim Gal (Centre for Human Drug Research)
Koos Burggraaf (Centre for Human Drug Research)
Michiel Kemme (vumc)
Gerard van Westen (LACDR)

Abstract:
QT interval assessment is a pivotal step in the development of novel compounds, but the thorough QT study is under debate. The present analysis evaluated the effect of the number of short term ECG replicates extracted from a continuous ECG recording on the assessment of the QT interval and the effect of different QT correction formulas. Aims The aim of the present analysis was to demonstrate the feasibility of a novel approach in which several epochs extracted from a continuous ECG recording were used to assess the compound’s effect on the QT interval. The optimal number of ECG epochs (replicates) required to asses this effect were investigated. In addition, different QT correction formulas were compared. Methods For one hundred healthy volunteers, who received a compound prolonging the QT interval, 18 ECG replicates within a 3 minute window were extracted from 12-lead Holter ECGs. Ten QT correction formulas were deployed and the QTc interval was controlled for baseline and placebo and averaged per dose level. Results / Conclusions The mean prolongation difference was >4 ms for single and > 2 ms for triplicate ECG measurements compared to the 18 ECG replicate mean value. The difference was <0.5ms (10 % of the safety limit) after 14 replicates. In contrast, concentration-effect analysis was independent of both the replicate number and correction formula.