Revefenacin, a Long‐Acting Muscarinic Antagonist, Does Not Prolong QT Interval in Healthy Subjects: Results of a Placebo‐ and Positive‐Controlled Thorough QT Study

Figures

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  Figure 1. Effect of revefenacin on heart rate (HR). Mean ± SE placebo‐corrected change from baseline HR (ΔΔHR) across postdose times. Data points are shown at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose. bpm, beats per minute; h, hours; SE, standard error.

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  Figure 2. Effect of revefenacin on QTc. Least‐squares mean (±95%CI change) from baseline QTcF (ΔQTcF) by time and treatment. Data points are shown at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose. CI, confidence interval; h, hours; HR, heart rate; msec, milliseconds; QTcF, QT interval corrected for heart rate using Fridericia's formula.

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  Figure 3. Plasma concentrations of (A) revefenacin and (B) THRX‐195518 across 24 hours following administration of inhaled single doses of revefenacin 175 and 700 µg. Data points are shown at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose. h, hours.

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  Figure 4. Model‐predicted ΔΔQTcF (mean and 90%CI) and observed ΔΔQTcF across deciles of revefenacin plasma concentrations. Blue and red circles denote the observed ΔΔQTcF for revefenacin 175 and 700 µg, respectively. The solid black line with gray‐shaded area denotes the model‐predicted mean ΔΔQTcF with 90%CI. ΔΔQTcF, placebo‐corrected change from baseline QT interval corrected for heart rate using Fridericia's formula; CI, confidence interval; msec, milliseconds.

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  Figure 5. Model‐predicted ΔΔQTcF (mean and 95%CI) and observed ΔΔQTcF (mean and 95%CI) across deciles of revefenacin plasma concentrations. Blue and red circles with vertical bars denote the observed mean ΔΔQTcF with 95%CI displayed at the median plasma concentration within each decile for 175 and 700 µg revefenacin, respectively. The solid black line with gray‐shaded area denotes the model‐predicted mean ΔΔQTcF with 95%CI. The horizontal blue and red lines with notches show the range of concentrations divided into deciles for revefenacin 175 and 700 µg, respectively. ΔΔQTcF, placebo‐corrected change from baseline QT interval corrected for heart rate using Fridericia's formula; CI, confidence interval; msec, milliseconds.