Evaluation of the Effect of Maribavir on Cardiac Repolarization in Healthy Participants: Thorough QT/QTc Study

Figures

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  Figure 1. Study schematic. F indicates overnight fast; E indicates pharmacokinetic (PK), echocardiogram (ECG), and safety evaluation (≤ 22 hours). Safety population (N = 52) included all participants who received at least one dose of the study drug (maribavir, moxifloxacin or placebo). PK population (N = 52) included all participants who received at least one dose of the study drug and had sufficient plasma concentration to calculate the primary PK parameters. ECG population (N = 52) included all participants who received at least one dose of the study drug and had at least one baseline (predose) ECG and on‐treatment (postdose) ECG within the same treatment period. PK/pharmacodynamic population included all participants in the ECG population with time‐matched plasma concentrations.

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  Figure 2. LS mean and 90% CI for time‐matched, placebo‐corrected, baseline‐adjusted corrected QT interval (ddQTc) (ms) vs. time after administration of maribavir (100 mg or 1,200 mg) or moxifloxacin (400 mg) (electrocardiographic PD population); (a) individualized corrected QT interval (ddQTcIb); (b) Fridericia‐corrected QT interval (ddQTcF) (ms). Dashed horizontal lines are reference lines depicting 0, 5, and 10 ms. CI, confidence interval; LS, least squares; PD, pharmacodynamic; QTcF, QT interval corrected using Fridericia’s formula; QTcIb, QT interval corrected individually with placebo QT–RR data.

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  Figure 3. Relationship between maribavir and metabolite plasma concentration and change in time‐matched, placebo‐corrected, baseline‐adjusted QT interval from the linear mixed‐effects PK–PD model for (a) maribavir and ddQTcIb, (b) maribavir and ddQTcF, (c) VP 44469 and ddQTcIb, and (d) VP 44469 and ddQTcF. The solid line with shaded area represents the PK–PD model‐predicted mean change in ddQTcIb or ddQTcF and the 90% confidence interval as a function of maribavir or VP 44469 plasma concentration. Dashed horizontal lines are reference lines depicting 10 ms and 20 ms of ddQTc change. Box plots display the distribution of predicted ddQTcIb or ddQTcF at each concentration decile. Circles represent individual data points from pooled data from 100‐mg and 1,200‐mg maribavir dose cohorts. ddQTcF, time‐matched, placebo‐corrected, baseline‐adjusted Fridericia‐corrected QT interval; ddQTcIb, time‐matched, placebo‐corrected, baseline‐adjusted individualized corrected QT interval; PD, pharmacodynamic; PK, pharmacokinetic.