PI-012

A. Khatri, S. Dutta, U. Das, E. Coakley, T. Podsadecki, W. Awni, R. Menon; AbbVie, North Chicago, IL

BACKGROUND: The all-oral IFN-free 3 direct acting antiviral (DAA) combination (3D) of ABT-450/r (protease inhibitor identified by Abbvie and Enanta, dosed with ritonavir), ombitasvir (NS5A inhibitor) and dasabuvir (NS5B polymerase inhibitor) ± ribavirin (RBV) has been evaluated in six Phase III trials in HCV genotype (GT) 1 infected subjects. The 2D (ABT-450/r + ombitasvir) ± RBV has been evaluated in HCV GT1b/4 infected subjects. This study assessed pharmacokinetics (PK), safety and tolerability of coadministration of pravastatin and rosuvastatin with 3D and 2D.
METHODS: Single doses of 3D or 2D were administered in Period 1. After a washout, multiple doses of pravastatin (10 mg QD, N=12) and rosuvastatin (5 mg QD, N=12) were administered with and without 3D or 2D to steady state in Period 2. DAA doses were: ABT-450/r 150/100 mg QD, ombitasvir 25 mg QD and dasabuvir 400 mg BID. Intensive PK sampling was performed in both periods and PK parameters estimated by noncompartmental analyses. Safety was evaluated through assessment of adverse events, vital signs, ECG and clinical laboratory tests.
RESULTS: Pravastatin and rosuvastain had no clinically significant effect on 3D or 2D-Cmax and AUC of ABT-450 were < 60% higher, ritonavir were ± 37% different, ombitasvir and dasabuvir were ± 12% different. Pravastatin Cmax and AUC were about 40% and 80% higher, respectively, with 3D or 2D. Rosuvastatin Cmax and AUC were 613% and 159% higher, respectively, with 3D, and 161% and 32% higher, respectively, with 2D. No new or unexpected safety findings were observed.
CONCLUSION: No dose adjustment is necessary for the 3D or 2D regimen during coadministration with pravastatin or rosuvastain. Pravastatin dose should be reduced by 50% and rosuvastatin dose should be no more than 10 mg/day during coadministration with 3D or 2D.