Grazoprevir/Ruzasvir/Uprifosbuvir versus Omeprazole
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Study Design
This was a 2-period, fixed-sequence, open-label drug-interaction study in 14 healthy males and females. On Day 1 of Period 1, a single oral dose of MK-3682B (2 x [50 mg Grazoprevir (GZR) / 30 mg Rusasvir (RZR) / 225 mg uprifosbuvir (UPR) FDC tablets) was administered. In Period 2, multiple oral once-daily doses of omeprazole (1 x 40 mg omeprazole capsule) were administered for 5 consecutive days; on Day 5, the single oral dose of omeprazole was administered 2 hours prior to a single oral dose of MK-3682B. The washout period was 7 days between the last dose of MK-3682B in Period 1 and the first dose of omeprazole in Period 2. Blood samples were collected for PK analysis of MK-3682B components. PK parameter values were calculated for all analytes by noncompartmental analysis. Geometric mean ratios (GMR) and 90% confidence intervals (CI) were calculated from the log transformed AUC0-∞, AUC0-24, Cmax, and C24 using linear mixed effect modelling. Safety was monitored throughout the study.
Study Results
Co-administration of omeprazole with MK-3682B did not meaningfully affect the PK of components of MK-3682B. Mean GZR and RZR AUC0-∞ increased ~25%. UPR AUC0- ∞, Cmax, and C24 remained unchanged (<5% decrease). Exposures of M6, the major circulating metabolite of UPR, remained unchanged (<10% difference in AUC, Cmax, and C24). The co-administration of omeprazole with MK-3682B in this study was generally well tolerated.
Study Conclusions
The author’s concluded that multiple doses of omeprazole did not meaningfully affect the pharmacokinetics of a single dose of MK-3682B. These results support co-administration of MK-3682B with omeprazole.
References
Arrington L, Gao W, Glasgow X, Luk J, Panebianco D, Rizk M. No clinically significant interaction between the proton pump inhibitor omeprazole with the components of mk-3682b. International Workshop On Clinical Pharmacology Of Antiviral Therapy . Chicago, IL, USA. 18; June 2017.
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