Results: ACH-3422 alone showed potency up to 7-fold

greater than the sofosbuvir comparator against genotype-1 through genotype-4 replicons. Short-term combination studies of ACH-3422 with RBV, ACH-3102, sovaprevir, or ACH-2684 showed additive to synergistic effects on antiviral potency. In long-term colony-formation studies, ACH-3422 treatment alone at a concentration approximately 8-fold above its EC50 value led to nearly complete blockage of resistance emergence. The same effect was achieved at lower ACH-3422 concentrations when combined with either ACH-3102 or an NS3 protease inhibitor (sovaprevir or ACH-2684). Further reduction of ACH-3422 concentrations to as low as its EC50 of 60 nM also completely blocked resistance emergence when selleck compound combined with both ACH-3102 and an NS3/4A protease inhibitor (either sovaprevir or ACH-2684). Conclusions: Combinations of ACH-3422 with an NS5A inhibitor, an NS3 protease inhibitor, or both were highly effective in blocking the emergence click here of resistant variants in vitro. These results support clinical investigation of ACH-3422 in combination with ACH-3102 and/or an NS3 protease inhibitor for the treatment of chronic hepatitis C. Disclosures: Jason Wiles – Employment: Achillion

Pharmaceuticals Mingjun Huang – Employment: Achillion Pharmaceuticals Wengang Yang – Employment: Achillion Pharmaceuticals; Stock Shareholder: Mirabegron Achillion Pharmaceuticals The following people have nothing to disclose: Dharaben Patel, Yongsen Zhao, Joanne L. Fabrycki, Guangwei Yang, Steven Podos, Avinash Phadke Purpose: Evaluate the pharmacokinetics and safety of ABT-493 and ABT-530 following 3-day monotherapy in HCV Geno-type-1 infected subjects with or without compensated cirrhosis.

Methods: This study is a randomized, open-label, multicenter dose-ranging study, exploring the safety, pharmacokinetics and antiviral activity of ABT-493 (100, 200 (including cirrhotics), 300, 400, and 700 mg QD) and ABT-530 (15, 40, 120 (including cirrhotics) and 400 mg QD) 3-day monotherapy in HCV genotype-1 infected subjects with or without compensated cirrhosis. Intensive blood samples were collected during the 3-day monotherapy for ABT-493 and ABT 530 pharmacokinetic assessment. Safety and tolerability was assessed throughout the study. Results: A total of 48 subjects received ABT-493 and 40 subjects received ABT-530. Both ABT-493 and ABT-530 showed rapid absorption with Tmax ranging from 2-4 hours. Similar to healthy subjects, increase in ABT-493 exposure was more than dose-proportional; Cmax and AUC24 ranged from 68.3 -12200 ng/mL and 290-71600 ng*h/mL over the 100-700 mg dose range. ABT-493 exposures in HCV infected non-cirrhotic subjects were 2- to 5-fold of healthy subjects, while exposure in subjects with cirrhosis were 6-fold of non-cir-rhotic subjects.