2008
DOI: 10.1038/clpt.2008.33
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The Effect of Moxifloxacin on QTc and Implications for the Design of Thorough QT Studies

Abstract: A number of issues have remained unanswered in the design of "thorough QT"(TQT) studies. In this randomized, placebo-controlled, two-period crossover study in 20 healthy subjects, replicate electrocardiograms (ECGs) were recorded on a digital 12-lead Holter recorder, extracted in a core ECG laboratory, and interpreted manually by a cardiologist. The observed within-subject variability was slightly greater when time-matched baselines were employed than when predose baselines were employed, whereas the magnitude… Show more

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Cited by 143 publications
(167 citation statements)
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“…The respective values for QT c B and QT c S were 425.3 ms (SD = 20.6 ms) and 415.2 ms (SD = 17.7 ms). Moxifloxacin administration on day 1 increased QT c F by 5.6 ms (90% CI, 1.9-9.3), which was within the expected range (22,29,30). The increase in QT c B with moxifloxacin was 11.1 ms (90% CI, 5.3-16.9) and the observed prolongation of QT c S was 5.7 ms (90% CI, 2.0-9.4).…”
Section: Corrected Qt Intervalsmentioning
confidence: 52%
“…The respective values for QT c B and QT c S were 425.3 ms (SD = 20.6 ms) and 415.2 ms (SD = 17.7 ms). Moxifloxacin administration on day 1 increased QT c F by 5.6 ms (90% CI, 1.9-9.3), which was within the expected range (22,29,30). The increase in QT c B with moxifloxacin was 11.1 ms (90% CI, 5.3-16.9) and the observed prolongation of QT c S was 5.7 ms (90% CI, 2.0-9.4).…”
Section: Corrected Qt Intervalsmentioning
confidence: 52%
“…However, some studies involving Caucasian subjects showed larger QTcF effects [15][16][17] . Therefore, further studies are required to determine ethnicity-specific effects, especially prospectively designed direct comparisons of moxifloxacininduced QT prolongation in Asians versus Caucasians.…”
Section: Discussionmentioning
confidence: 99%
“…However, this dedicated QTc study incorporated many of the key guidance directives, including the following: (a) characterization of the response relationship using exposures higher than those achieved at the therapeutic dose, that is, the use of a supratherapeutic dose; (b) using replicate ECGs to reduce variability; (c) using a centralized core laboratory blinded to time and treatment to reduce bias and variability; (d) utilization of placebo control; (e) utilization of a crossover design with each patient serving as his/her own control; and (f) drug concentration measurements collected at the time of ECG assessment to aid in concentration-response relationships. This study was done in patients with advanced cancer, the targeted therapeutic population, and use of a positive control such as moxifloxacin that prolongs the mean QTc interval (17) was not acceptable due to the overall poor health status of the study population. Patients with advanced cancer may harbor disease or therapy-related cardiac, renal, and metabolic abnormalities, which may pose a greater risk for QT prolongation.…”
Section: Discussionmentioning
confidence: 99%
“…The study lacked a positive control that limits assessment of assay sensitivity; however, past clinical experience with similar monitoring techniques have consistently shown positive findings of QTc prolongation with positive controls (such as moxifloxacin), suggesting that this may not be a major deficiency (15,(17)(18)(19)(20)(21). Additionally, blood draws during placebo administration were not done, which may have led to potential unblinding of study therapy to patients.…”
Section: Discussionmentioning
confidence: 99%