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Abstract:
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COVID-19, an infectious disease caused by the SARS-CoV-2 virus, was declared a global pandemic by WHO in March 2020. MOV is an oral antiviral COVID-19 treatment that has received Emergency Use Authorization by FDA. C-QTc modeling is used early in drug development to determine if there is a risk of QTc prolongation associated with the drug. As part of the safety evaluation of MOV, intensive QT assessment was performed in a Phase 1 clinical trial using data collected by 12-lead Holter ECGs at timepoints corresponding to PK draw following single and multiple dose administration up to and exceeding 800 mg Q12H. Following (Garnett, et al, 2018), mixed effects modelling was performed to assess the relationship between individual QTc change from baseline and the plasma concentration of the active circulating metabolite of MOV. The model included fixed effects for treatment, timepoint, Fridericia’s corrected QTcF baseline (continuous), concentration (continuous) and random effects for the intercept and slope. Overall, NHC did not prolong QTc at concentrations observed with doses up to 1600 mg providing approximately a 2.14-fold margin to the highest clinical dose (800 mg Q12H) of MOV.
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