Scientific Publications by FDA Staff
Drug Saf 2014 Mar;37(3):183-9
Impact of Electrocardiographic Data Quality on Moxifloxacin Response in Thorough QT/QTc Studies.
Johannesen L, Garnett C, Malik M
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.
|Category: Journal Article|
|PubMed ID: #24554350||DOI: 10.1007/s40264-014-0142-2|
|Includes FDA Authors from Scientific Area(s): Medical Devices Drugs|
|Entry Created: 2014-02-21||Entry Last Modified: 2014-04-05|