Conclusion:Male patients and those with a higher body weight were more likely to receive non-standard doses of RBV, likely reflecting the perception that this may lead to higher rates of SVR.The impact of higher RBV doses on relapse and SVR will be determined after ongoing follow-up in this study.

Methods: Results from two Phase 1 studies were pooled for the analysis.Study 1 investigated the antiviral activity of oral filibuvir doses of 100, 300 and 450 mg BID and 300 mg TID or placebo, for 8 days in treatment naïve patients.In the second study, the antiviral activity of filibuvir 450 mg BID in treatment experienced patients dosed for 10 days and 700 mg BID in treatment naïve patients dosed for 3 days was evaluated.Filibuvir exposures achieved over 24 hours (AUC24) were utilized to inform the ER analysis of the maximum log change in viral load from baseline.The relationship was described by an inhibitory E max model using a non-linear mixed effects model.Effects of food, baseline viral load (BVL) and genotype (1a/1b) on relevant model parameters were also evaluated.The antiviral response for a range of doses was simulated from the model. Results:The ER data from 52 subjects were adequately described by the E max model with E max (95% CI) = -2.14(-2.54, -2.02) IU/ml and AUC24 50 (95% CI) = 54,176 (44,606, 102,006) ng•hr/ml.BVL was the only influential covariate which described the maximal response (E max ).The analysis indicated that doses in excess of 300 mg BID were expected to achieve atleast 70% of E max .Furthermore, filibuvir exposures resulting from doses greater than 600 mg BID produced responses close to E max indicating that higher doses (>600 mg BID) are unlikely to provide additional efficacy.Conclusions: Filibuvir exposures adequately described the maximum log change in viral load relative to baseline.The above analysis in conjunction with results from a Phase 2a study (200/300/500 mg BID+SOC, rapid viral response rates of 60-75%) suggests that filibuvir doses of 300 and 600 mg BID are expected to be efficacious when combined with SOC and will be further investigated in Phase 2b studies.