Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir + Lopinavir/Ritonavir = Prohibited

Study Design

This was a phase 1, randomized, multiple-dose, open label, single center study to evaluate drug-drug interactions between paritaprevir/ritonavir/ombitasvir + dasabuvir (ABT-450/r/ABT-267 + ABT-333, also known as 3D regimen) and lopinavir/ritonavir (LPV/r), when administered together for 14 days in healthy subjects. The 3D drugs were dosed as paritaprevir/ritonavir 150/100mg QD, ombitasvir 25mg QD, and dasabuvir 400mg BID. LPV/r was administered as 800/200mg QD in the evening or 400/100mg BID.Blood samples for pharmacokinetic (PK) analysis were collected following dosing of 3D regimen alone, LPV/r alone, and the combination of the two.

Study Results

Using Least Squares Mean (LSM) ratios and 90% confidence intervals (90% CI), the Cmax, AUC and Ctrough for LPV when coadministered with the 3D regimen were 0.86 (0.80-0.93), 0.94 (0.87-1.01) and 3.18 (2.49-4.06), respectively, when dosed in the evening. When dosed twice daily, the LPV Cmax, AUC and Ctrough were 0.87 (0.76-0.99), 0.94 (0.81-1.10) and 1.15 (0.93-1.42), respectively. The LSM ratios (90% CI) for the 3D regimen coadministered with LPV dosed in the evening were as follows:The Cmax, AUC and Ctrough for paritaprevir were 0.99 (0.79-1.25), 1.87 (1.40-2.52) and 8.23 (5.18-13.07), respectively. Those for ritonavir were 1.57 (1.34-1.83), 2.62 (2.32-2.97) and 19.46 (15.93-23.77). Those for ombitasvir were 0.87 (0.83-0.92), 0.97 (0.94-1.02) and 1.11 (1.06-1.16). Those for dasabuvir were 0.56 (0.47-0.66), 0.54 (0.46-0.65) and 0.47 (0.39-0.58), respectively.The LSM ratios (90% CI) for the 3D regimen with twice-daily boosted LPV were as follows:The Cmax, AUC and Ctrough for paritaprevir were 2.04 (1.30-3.20), 2.17 (1.63-2.89) and 2.36 (1.00-5.55), respectively. Those for ritonavir were 1.55 (1.16-2.09), 2.05 (1.49-2.81) and 5.25 (3.33-8.28). Those for ombitasvir were 1.14 (1.01-1.28), 1.17 (1.07-1.28) and 1.24 (1.14-1.34). And those for dasabuvir were 0.99 (0.75-1.31), 0.93 (0.75-1.15) and 0.68 (0.57-0.80), respectively.There were no discontinuations due to adverse effects.The authors do not recommend coadministration of the 3D regimen with LPV/r.

Study Conclusions

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 hiv protease inhibitors. 54th Interscience Conference On Antimicrobial Agents And Chemotherapy. Washington, DC. ; 2014.