Evaluation of the Cardiac Safety of Long-Acting Endectocide Moxidectin in a Randomized Concentration-QT Study

Sally A Kinrade, Jay W Mason, Carlos R Sanabria, Craig R Rayner, Julie M Bullock, Stephanie H Stanworth, Mark T Sullivan, Sally A Kinrade, Jay W Mason, Carlos R Sanabria, Craig R Rayner, Julie M Bullock, Stephanie H Stanworth, Mark T Sullivan

Abstract

Potential effects on cardiac repolarization of single doses of moxidectin, a potent long-acting macrocyclic lactone endectocide, were assessed in a concentration-QT (c-QT; exposure-response) study. This double-blind, placebo-controlled, parallel-group study in healthy male volunteers (n = 60) randomized subjects to a single oral dose of moxidectin (4 mg, 8 mg, 16 mg, 24 mg, or 36 mg) or matching placebo. Serial plasma samples for pharmacokinetic (PK) analysis and concurrent triplicate electrocardiogram measurements were taken at baseline and 14 prespecified time points over 72 hours, yielding 900 QT interval-plasma concentration time-matched pairs. Moxidectin had no statistically significant or clinically relevant impact on QT interval at any dose level. The primary mixed effects model analysis revealed no treatment-related impact on the Fridericia-corrected QT interval-plasma concentration gradient (-0.0077, 90% confidence interval (CI) -0.0255 to +0.0101).

Trial registration: ClinicalTrials.gov NCT03012828.

© 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1
Figure 1
Mean ± SD moxidectin plasma concentration (ng/mL) vs. time (linear scale).
Figure 2
Figure 2
Scatterplot and linear regression for QTcF interval vs. the RR interval is the time between QRS complexes, a measure of heart rate.
Figure 3
Figure 3
The ΔQTcF interval vs. time by dose of moxidectin (mean and two‐sided 90% confidence interval (CI).
Figure 4
Figure 4
Linear regression model of ΔΔQTcF (in milliseconds) vs. moxidectin concentrations derived from all concentration‐QTcF pairs and showing observed median‐decile plasma moxidectin concentrations and associated mean ΔΔQTcF with 90% confidence interval (CI).

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