Dasabuvir/ombitasvir/paritaprevir/ritonavir vs efavirenz, emtricitabine/tenofovir disoproxil fumarate, or dasabuvir/ombitasvir/paritaprevir/ritonavir
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Study Design
This was a phase 1, randomized, multiple-dose, open label, single center study to evaluate drug-drug interactions between paritaprevir/ritonavir + dasabuvir (ABT-450/r + ABT-333, also known as 2D regimen) and efavirenz (EFV), when administered together in healthy subjects. The 2D drugs were dosed as paritaprevir/ritonavir 150/100mg QD and dasabuvir 400mg BID. EFV was administered as Atripla (efavirenz/tenofovir/emtricitabine 600/300/200 mg), given QD. In cohort 1 (n=9), the 2D regimen was given alone on day 0-14 followed by 2D regimen + Atripla on day 14-28. In cohort 2 (n=7), Atripla was given alone on day 0-14 followed by 2D regimen + Atripla on day 14-28. All doses were administered under non-fasting conditions.
Study Results
Using Least Squares Mean (LSM) ratios and 90% confidence intervals (90% CI), the Cmax, AUC and Ctrough for TDF when coadministered with the 3D regimen were 1.07 (0.93-1.24), 1.13 (1.07-1.20) and 1.24 (1.13-1.36), respectively. Those for FTC were 1.05 (1.00-1.12), 1.07 (1.00-1.14) and 1.09 (1.01- 1.17), respectively when coadministered with the 3D regimen. LSM ratios (90% CI) for the 3D regimen when coadministered with TDF/FTC were as follows:The Cmax, AUC and Ctrough for paritaprevir were 0.68 (0.42-1.11), 0.84 (0.59-1.17) and 1.06 (0.83-1.35) respectively. Those for ritonavir were 0.83 (0.66-1.05), 0.95 (0.80-1.13) and 0.97 (0.88-1.06), respectively. Those for ombitasvir were 0.89 (0.81-0.97), 0.99 (0.93-1.05) and 0.97 (0.90-1.04). And those for dasabuvir were 0.85 (0.74-0.98), 0.85 (0.75-0.96) and 0.85 (0.73-0.98), respectively.
Study Conclusions
Coadministration of the 3D regimen with TDF/FTC was generally well tolerated and there were no study discontinuations.No dose adjustments are required when utilizing this combination.
References
A Khatri, T Wang, H Wang, et al. Drug-drug interactions of the direct acting antiviral regimen of abt-450/r, ombitasvir, and dasabuvir with emtricitabine tenofovir, raltegravir, rilpivirine and efavirenz. 54th Interscience Conference On Antimicrobial Agents And Chemotherapy. Washington, DC. ; 2014.
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