Treatment with Volanesorsen, a 2′-O-Methoxyethyl-Modified Antisense Oligonucleotide Targeting APOC3 mRNA, Does Not Affect the QTc Interval in Healthy Volunteers

Figures

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  FIG. 1.. Mean (±SD) plasma concentration of volanesorsen versus time following single SC and IV doses. IV, intravenous; SC, subcutaneous; SD, standard deviation.

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  FIG. 2.. Least squares mean (±90% CI) placebo-corrected change from baseline QTcF across time points. CI, confidence interval.

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  FIG. 3.. Joint plot of mean volanesorsen 300 mg SC plasma concentration and mean ΔΔQTcF over time (PK/QTc population).

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  FIG. 4.. Joint plot of mean volanesorsen 300 mg IV plasma concentration and mean ΔΔQTcF over time (PK/QTc population).

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  FIG. 5.. Relationship between individual volanesorsen concentrations and ΔΔQTcF with 90% CI (PK/QTc population). Prediction was based on Model 1.

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  FIG. 6.. Goodness-of-fit plot for observed and predicted relationship between volanesorsen levels and ΔΔQTcF (PK/QTc population). Analysis was based on PK/QTc population. Blue and red circles with vertical bars denote the observed mean ΔΔQTcF with 90% CI displayed at the median plasma concentration within each decile of volanesorsen on doses of 300 mg SC and 300 mg IV, respectively. The solid black line with gray shaded area denotes the model-predicted mean ΔΔQTcF with 90% CI. The horizontal blue and red lines with notches show the range of plasma concentrations divided into deciles for volanesorsen on doses of 300 mg SC and 300 mg IV, respectively.