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The effects of moxifloxacin on QTc interval in healthy Korean male subjects.

ABSTRACT: Moxifloxacin 400 mg is a widely used positive control in thorough QT (TQT) studies, but its QT-prolonging effects in Korean subjects have not been studied. The present study was conducted to collect pilot data in Korean subjects after moxifloxacin administration to evaluate the adequacy of moxifloxacin as a positive control.Thirty-eight, healthy, Korean, male subjects were recruited for pharmacokinetic (PK) blood sampling and electrocardiography (ECG) recordings at three different study sites. On day 1, a baseline 12-lead ECG was recorded, and on day 2, ECG recordings were conducted after placebo, or moxifloxacin 400- or 800-mg administration. Baseline-corrected, placebo-adjusted, corrected QT (ΔΔQTc) values were calculated. Blood samples were collected after moxifloxacin administration and PK parameters were assessed.A total of 33 subjects completed the study. The largest time-matched ΔΔQTc occurred approximately 4 h after dosing, with ΔΔQTcI (QT interval corrected by individual QT-RR regression model) values of 11.66 ms (moxifloxacin 400 mg) and 20.96 ms (800 mg). The mean and 90 % confidence intervals of ΔΔQTcI did not include zero at any of the measurement time points. There was a positive correlation between plasma moxifloxacin concentration and ΔΔQTcI (r = 0.422). Dose-proportional PK profiles were observed.Moxifloxacin 400 mg is an adequate positive control in Korean TQT studies. Our results indicate that moxifloxacin 400 mg can be used to evaluate the cardiac safety of a drug in Korean subjects.

SUBMITTER: Moon SJ

PROVIDER: S-EPMC4070463 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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The effects of moxifloxacin on QTc interval in healthy Korean male subjects.

Moon Seol Ju SJ Lee Jongtae J An Hyungmi H Yim Dong-Seok DS Chung Jae-Yong JY Yu Kyung-Sang KS Cho Joo-Youn JY Lim Kyoung Soo KS

Drugs in R&D 20140601 2

<h4>Background and objective</h4>Moxifloxacin 400 mg is a widely used positive control in thorough QT (TQT) studies, but its QT-prolonging effects in Korean subjects have not been studied. The present study was conducted to collect pilot data in Korean subjects after moxifloxacin administration to evaluate the adequacy of moxifloxacin as a positive control.<h4>Methods</h4>Thirty-eight, healthy, Korean, male subjects were recruited for pharmacokinetic (PK) blood sampling and electrocardiography ( ...[more]

PMID: 24691742

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Project description:AimsWe investigated the effect of gadopiclenol, a new gadolinium-based contrast agent, on the QTc interval at clinical and supraclinical dose, considering the relative hyperosmolarity of this product.MethodsThis was a single centre, randomized, double-blind, placebo- and positive-controlled, 4-way crossover study. Forty-eight healthy male and female subjects were included to receive single intravenous (i.v.) administrations of gadopiclenol at the clinical dose of 0.1 mmol kg-1 , standard for current gadolinium-based contrast agents, the supraclinical dose of 0.3 mmol kg-1 , placebo and a single oral dose of 400 mg moxifloxacin.ResultsThe largest time-matched placebo-corrected, mean change from-baseline in QTcF (ΔΔQTcF) was observed 3 hours after administration of 0.1 mmol kg-1 gadopiclenol (2.39 ms, 90% confidence interval [CI]: 0.35, 4.43 ms) and 5 minutes after administration of 0.3 mmol kg-1 (4.81 ms, 90%CI: 2.84, 6.78 ms). The upper limit of the 90% CI was under the threshold of 10 ms, demonstrating no significant effect of gadopiclenol on QTc interval. From 1.5 to 4 hours postdose moxifloxacin, the lower limit of the 90% CI of ΔΔQTcF exceeded 5 ms demonstrating assay sensitivity. Although there was a positive slope, the concentration-response analysis estimated that the values of ΔΔQTcF at the maximal concentration of gadopiclenol at 0.1 and 0.3 mmol kg-1 were 0.41 and 2.23 ms, respectively, with the upper limit of the 90% CI not exceeding 10 ms. No serious or severe adverse events or treatment discontinuations due to adverse events were reported.ConclusionThis thorough QT/QTc study demonstrated that gadopiclenol did not prolong the QT interval at clinical and supraclinical doses and was well tolerated in healthy volunteers. The positive slope of the QTc prolongation vs concentration relationship suggests that hyperosmolarity could be associated with QTc prolongation. However, the amplitude of this effects is unlikely to be associated with proarrhythmia.

Dataset Information

The effects of moxifloxacin on QTc interval in healthy Korean male subjects.

Publications

The effects of moxifloxacin on QTc interval in healthy Korean male subjects.

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