Impact of electrocardiographic data quality on moxifloxacin response in thorough QT/QTc studies.

Abstract:

BACKGROUND:Thorough QT studies are typically conducted for drugs with systemic bioavailability and include a positive control, typically moxifloxacin, with a well-described QTc effect. OBJECTIVE: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 a typical moxifloxacin time profile. METHODS:ECGs from 65 studies with available moxifloxacin plasma concentrations were obtained, including four studies with an unexpected moxifloxacin response. Residual error of a concentration-QT model was evaluated before and after re-measuring the QT interval based on ECG pattern similarity. Intra-replicate heart rate differences were calculated using the original heart rate measurements and the 10-s average heart rates. RESULTS:Similarity re-measurements reduced the residual error of the model (before vs. after of 8.43 ± 2.00 vs. 7.55 ± 1.86 ms; p < 0.001). For both original and averaged 10-s heart rate, intra-replicate heart rate differences were significantly lower (p < 0.001) in studies with the expected response than in those with an unexpected time profile. DISCUSSION:The pattern similarity measurement methodology reduces the residual error of the model, which influences the time profile of the moxifloxacin response. Accuracy of study conduct, represented by intra-replicate heart rate differences, separated studies with and without the expected moxifloxacin time profile.

journal_name

Drug Saf

journal_title

Drug safety

authors

Johannesen L,Garnett C,Malik M

doi

10.1007/s40264-014-0142-2

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

183-9

issue

3

eissn

0114-5916

issn

1179-1942

journal_volume

37

pub_type

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