SAN FRANCISCO, CA—Mild or moderate renal impairment did not impact direct-acting antivirals (DAA) and ritonavir (RTV) exposures, a study presented at The Liver Meeting® 2015 found.
Akshanth R. Polepally, PhD, and colleagues from AbbVie, North Chicago, IL, aimed to evaluate the effect of renal function on the pharmacokinetics of DAAs, RTV, and ribavirin (RBV), in hepatitis C virus (HCV) genotype 1 (GT1) subjects.
Pooled data from six Phase 3 studies and one Phase 2 study, which enrolled >2,000 HCV GT1 infected subjects was used to generate area under the plasma concentration curve (AUC) for total exposure. Study subjects received ombitasvir/paritaprevir/ritonavir 25mg/150mg/100mg daily and dasabuvir 250mg twice daily (3D regimen) ± weight-based RBV. A total of 1,495 subjects had normal renal function (CrCl ≥90mL/min), 576 had mild renal impairment (CrCl 60–89mL/min), and 22 had moderate renal impairment (CrCl 30–59mL/min).
“The effect of CrCl on the AUC values of each DAA, RTV, and RBV was evaluated and adjusted for any significant subject-specific covariates including, age, sex, body weight, cirrhosis, and Asian ethnicity in multiple linear regression analysis,” explained Dr. Polepally.
Study results showed that CrCl was not a statistically significant predictor of DAAs and RTV AUC values (P>0.05). Covariates such as age, sex, and cirrhosis were significant for all DAAs and RTV whereas body weight and Asian ethnicity were significant for ombitasvir and dasabuvir. There was a significant correlation with CrCl and RBV AUC values (P<0.05), which was consistent with RBV’s primary renal excretion.
For RBV, age, sex, body weight, and cirrhosis were significant covariates. AUC values for the DAAs were comparable (≤10% difference) among different levels of renal function, whereas RBV AUC values were up to 17% higher in mild or moderate renal impairment vs. normal function.
Findings from the study support that no dose adjustments are needed for the 3D regimen as a <10% increase in total exposure is expected. Ribavirin doses, however, should be adjusted for renal impairment according to its label, added Dr. Polepally.