Period correction of the QTc of moxifloxacin with multiple predose baseline ECGs is the least variable of 4 methods tested.
This study compares 4 baseline correction methods on the effect of moxifloxacin on the QT/QTc interval: (1) day -1 time-matched baseline electrocardiograms (ECGs), (2) 3 triplicate predose ECGs, (3) 1 triplicate predose ECG, and (4) no baseline correction. Forty-four healthy subjects receive a single dose of moxifloxacin (400 mg), placebo, and 2 doses of an investigational agent in a 4-period crossover fashion. For all 4 methods, the largest mean difference from placebo in the moxifloxacin study-specific QTc is 11.97 to 13.23 ms and occurs at 3 to 4 hours postdose; the lower 90% confidence interval is greater than 5 ms from 2 to 8 hours. The average standard error of the mean is 1.36 ms for 3 triplicate predose ECGs, 1.40 ms for 1 triplicate predose ECG, 1.60 ms for day -1 time-matched baseline ECGs, and 1.65 ms for no baseline correction. Predose baseline methods (3 or 1 triplicate ECGs) are superior to the day -1 time-matched baseline correction or without baseline correction.
Zhang
Xiaoping
X
Department of Clinical Pharmacology, Hoffman-La Roche Inc, Nutley, NJ 07110, USA. Amy.zhang@roche.com
Silkey
Mariabeth
M
Schumacher
Marta
M
Wang
Lei
L
Raval
Hiral
H
Caulfield
John P
JP
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin