In the Phase I study in healthy volunteers, ANA598 was administered as capsules at single doses starting at 400mg. At the 2000mg dose level, it was administered during fasting and also following a meal. In addition, a separate cohort received two 800mg doses 12 hours apart. ANA598 was well tolerated at all doses analyzed to date and no serious adverse events were reported.
The pharmacokinetic profile demonstrated sustained plasma levels of ANA598 with a half-life of more than 24 hours, consistent with the potential for once-daily or twice-daily oral dosing. All doses achieved plasma drug concentrations predicted to display substantial antiviral activity based on preclinical results. Additionally, absorption was enhanced when ANA598 was taken with food, indicating that it should not be necessary to take ANA598 on an empty stomach in order to achieve desired plasma drug levels.
Anadys is now finalizing preparations to begin a Phase Ib trial of ANA598 in HCV patients early in the fourth quarter. The study will be conducted at several sites in the US. The regulatory review necessary to initiate the study has been completed.
In the Phase Ib monotherapy study, naive genotype 1 patients will receive ANA598 over three days, at doses of 200mg bid, 400mg bid or 800mg bid. Ten patients are planned to be enrolled in each of the three cohorts, eight on active treatment and two on placebo. Anadys expects to have viral load data from all three cohorts in the first quarter of 2009. Anadys may elect to explore other dose levels of ANA598 or once-daily dosing in this study, depending on data from the first three cohorts.