Coadministration of SOF with GS-5816 did not alter GS-5816 PK. Conclusion Coadministration of SOF and GS-5816 was generally well tolerated.

Sofosbuvir and GS-5816 may be coadministered without dose adjustment. Disclosures: Erik Mogalian – Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc Polina German – Employment: GIlead Sciences, Inc; Stock Shareholder: GIlead Sciences, Inc Diana M. Brainard – Employment: Gilead Sciences, Inc. John O. Link – Employment: Gilead Sciences; Patent Held/Filed: Gilead Sciences; Stock Shareholder: Gilead Sciences, Pfizer John McNally- Employment: Gilead Sciences, Inc Brian P. Kearney- Employment: Gilead Sciences The following people have nothing to disclose: Lingling Han Background: Faldaprevir (FDV) see more is a potent HCV NS3/4A protease inhibitor. In combination with pegylated interferon alfa-2a and ribavirin (RBV), or with BI 207127 and RBV, FDV has demonstrated high sustained virologic response rates in treatment-naïve patients with chronic HCV genotype 1 (GT1) infection. Here, we have assessed the

pharmacokinetics (PK) and safety of a single dose of FDV in subjects with varying levels of renal impairment. Methods: HCV-negative subjects (18-75 years) with renal impairment (mild to severe based on estimated glomerular filtration rate [eGFR]), and healthy controls, were given a single oral dose of FDV 480 mg after a 10-hour overnight fast. PK and safety assessments were performed over a 144-hour period after dosing. Results: 32 subjects (mean age 61.4 years; 21 males) completed the study. Due to mild LY294002 mw vomiting events, 8 subjects were excluded from the primary PK analysis. Geometric mean (gMean) peak (Cmax) and total (AUC0 J exposures of FDV were highest in subjects with moderate renal impairment (Table). Compared with Levetiracetam subjects with normal renal function, the statistical analysis showed that adjusted gMean ratios (90% CI) for AUC0-∞ were 1.14 (0.42-3.10), 1.78 (0.85-3.73),

and 1.69 (0.73-3.91) for subjects with mild, moderate, or severe renal impairment, respectively. The gMean ratios for C were 1.07 (0.35-3.27), 1.76 (0.90-3.44), and 1.21 (0.47-3.10). Median tmax was 4 hours for all groups. There was no difference in the free fraction of FDV (not bound to plasma proteins) for subjects with any renal impairment versus those with normal renal function. Although renal impairment increased peak and total exposure, no correlation between either AUC0-∞ or Cmax and eGFR was found. Overall, 5/8 (63%) subjects with normal renal function and 20/24 (83%) subjects with renal impairment reported adverse events. There were no notable differences in treatment tolerability between subjects with normal renal function and those with renal impairment. Conclusions: Moderate or severe renal impairment can result in a modest increase in exposure to FDV.