QT Interval Shortening With Isavuconazole:In VitroandIn VivoEffects on Cardiac Repolarization

Figures

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  Figure 1. Subject disposition in the phase I clinical study. *Equivalent to the therapeutic dose of isavuconazonium sulfate 372 mg. †Equivalent to supratherapeutic dose isavuconazonium sulfate 1,116 mg.

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  Figure 2. Mean change compared with placebo in baseline‐adjusted* QTcF over time on Day 13 in the phase I clinical study. Error bars represent 90% CI. QTcF, Fridericia‐corrected QT interval; ddQTcF, time‐matched, drug–placebo difference in QTcF interval, baseline‐adjusted. Zero on x‐axis represents time of Day 13 dose; horizontal dotted line represents threshold for significant prolongation of QTcF interval. *Baseline was defined as time‐matched measurement on Day −1.

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  Figure 3. Mean ( ± standard deviation) plasma concentrations of isavuconazole (a) and moxifloxacin (b) following the Day 13 dose in the phase I clinical study.

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  Figure 4. Scatterplot of individual dQTcF vs. isavuconazole plasma concentration in the phase I clinical study. C max, maximum concentration; dQTcF, time‐matched, baseline‐adjusted QTcF interval; QTcF, Fridericia‐corrected QT interval. Postdose timepoints are shown at 200 mg (□) and at 600 mg isavuconazole (+). Dashed lines represent predicted dQTcF at the Cmax for 200‐mg and 600‐mg doses, shown with 90% CI.