Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide versus Sofosbuvir/Velpatasvir
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Study Design
Nine cohorts in two phase I, open-label, randomized, multiple-dose cross-over studies in healthy volunteers compared the pharmacokinetics of sofosbuvir/velpatasvir (SOF/VEL) when given alone versus when this fixed dose combination was given with several antiretroviral medications. In the fifth cohort, 24 subjects were given SOF/VEL with a fixed dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (ELV/COBI/FTC/TAF). Steady state pharmacokinetic samples were collected over 24 hours on the last day of dosing for each treatment. Geometric Least Square Means Ratios and 90% confidence intervals (combination vs alone) were estimated and compared against a lack of PK alteration boundaries of 70 – 143% for all analyses. Safety of these medications was also evaluated using standard laboratory values and physical examination.
Study Results
Although specific PK values were not reported, the results showed that there was a statistically significant increase in geometric mean ratio values for AUCtau of SOF and it's metabolite, GS-331007 by approximately 40% and 50%, respectively, when co-administered with E/C/F/TAF. Similarly, PK parameters for VEL were also significantly increased with E/C/F/TAF co-administration (approximately 50% increase in AUCtau GMR of VEL).
There were no significant effects of SOF/VEL on the PK of EVG and FTC. TAF exposures were slightly reduced, while those for TFV (tenofovir derived from TAF) were slightly increased (by approximately 25%) when co-administered with SOF/VEL. There was also a statistically significant increase (~40%) in Cobi exposure observed.
The authors state that these PK changes are not clinically significant based on exposure-safety and -efficacy evaluations in Phase 3 SOF/VEL studies.
Study treatments were reported to be safe and well-tolerated.
Study Conclusions
According to the authors, there is no significant pharmacokinetic interaction between SOF/VEL and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, and coadministration of these agents can be done without concern. The increase in COBI ctau was not expected to introduce further drug interaction potential.
References
Mogalian E, McNally J, Shen G, Moorehead L, Sajwani K, Smith B, Mathias A. Drug-drug interaction profile of sofosbuvir/velpatasvir fixed-dose combination. Journal Of Hepatology. 2016; 2: S313-S314.
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