A. R. Polepally, S. Dutta, T. Baykal, B. Hu, T. J. Podsadecki, W. M. Awni, R. M. Menon; AbbVie Inc., North Chicago, IL
BACKGROUND: The all-oral IFN-free, 3 DAA combination (3D) of ABT-450/r (NS3 protease inhibitor identified by AbbVie and Enanta, coadministered with ritonavir) + ombitasvir (NS5A inhibitor) + dasabuvir (NS5B polymerase inhibitor) and 2D regimen (ABT-450/r + ombitasvir) ± ribavirin has been evaluated in HCV genotype (GT) 1 and GT1b/4-infected subjects, respectively. This study assessed pharmacokinetics (PK), safety and tolerability of coadministration of omeprazole (a CYP2C19 substrate and acid reducing agent) with the 3D and 2D regimens in healthy volunteers.
METHODS: In 24 healthy volunteers omeprazole (40 mg) was administered on day 1 and days 20-24. The 3D or 2D regimen (ABT-450/r 150/100 mg QD + ombitasvir 25 mg QD ± dasabuvir 250 mg BID) was administered on days 6-24. Intensive PK sampling was performed for study drugs when dosed alone and during coadministration and parameters estimated by non-compartmental analyses. Safety was evaluated through assessment of adverse events, vital signs, ECG and clinical laboratory tests.
RESULTS: Omeprazole coadministration did not affect (<20% change) the Cmax, AUC or Ctrough of ABT-450, ritonavir, ombitasvir or dasabuvir from the 3D and the 2D regimens. Coadministration of omeprazole with the 3D or 2D regimen resulted in ~40 to 50% decrease in omeprazole exposure probably due to mild CYP2C19 induction by ritonavir. No new or unexpected safety findings were observed.
CONCLUSION: No dose adjustment is necessary for the 3D or 2D regimen during coadministration with acid reducing agents. The decrease in omeprazole exposure when coadministered with the 3D or 2D regimen is not expected to have a clinically meaningful impact on omeprazole efficacy. Dose adjustment for omeprazole may not be necessary but an increased dose may be considered based on response.