Sofosbuvir/Velpatasvir versus Atorvastatin
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Study Design
This was an open-label, randomized, two-way crossover study in 26 healthy subjects. Subjects received a single dose of atorvastatin (40 mg) alone (Treatment A), or in combination with multiple-dose SOF/VEL (400/100 mg; Treatment B). PK sampling was performed for 72 hours following administration of atorvastatin, and safety was assessed throughout the study. Geometric-least squares means ratios (GLSM) and 90% confidence intervals (90%CI) were estimated for atorvastatin, and were compared against pre-specified lack of PK alteration boundaries of 70 to 143% (AUC) and 50-200% (Cmax). Exploratory PK analyses were performed for atorvastatin metabolites (atorvastatin lactone, o-hydroxyatorvastatin, phydroxyatorvastatin), SOF and its metabolites (GS-566500 and GS-331007) and VEL.
Study Results
Co-administration of SOF/VEL with atorvastatin resulted in higher atorvastatin AUC (↑59%) and Cmax (↑68%); similarly higher exposure of atorvastatin metabolites was also observed (ohydroxyatorvastatin AUC: ↑37%, Cmax: ↑11%; p-hydroxyatorvastatin AUC: ↑77%, Cmax: ↑41%; atorvastatin lactone AUC: ↑60%, Cmax: ↑82%). These results are consistent with inhibition of OATP and P-gp by VEL. Steady-state exposures of SOF, its metabolites and VEL were similar to historical values.
Study Conclusions
The author’s concluded that consistent with the previous characterization of VEL as an inhibitor of OATP and P-gp transporters, co-administration of SOF/VEL resulted in a ~60% increase in exposure of atorvastatin. All study treatments were well-tolerated.
References
Begley R, Mogalian E, McNabb B, Shen G, Lee S, Ling J. Evaluation of drug-drug interaction potential between sofosbuvir/velpatasvir and atorvastatin. International Workshop On Clinical Pharmacology Of Antiviral Therapy. Chicago, IL, USA. 18; June 2017.
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