Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate 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 sixth cohort, 24 subjects were given SOF/VEL with a fixed dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (ELV/COBI/FTC/TDF). 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 modest increase in geometric mean ratio values for AUCtau of SOF and it's metabolite, GS-331007 by approximately 25% and 40%, respectively, when co-administered with E/C/F/TDF. AUCtau GMR for VEL was slightly increased with E/C/F/TDF co-administration, by approximately 20%.
There were no significant effects of SOF/VEL on the PK of EVG and FTC. TFV (tenofovir derived from TDF) and Cobi exposures were modestly increased by approximately 40% and 30%, respectively.
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 disoproxil fumarate, led to an increase in tenofovir disoproxil fumarate exposures. However, no guidance has been offered regarding the potential drug interaction between SOF/VEL and tenofovir disoproxil fumarate, and clinical judgement should be utilized.
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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