"Result: Data from the 5, 10, 25, 50, and 100 mg cohorts in the healthy volunteer study shows CMX157 was rapidly absorbed and eliminated. Corresponding tmax and t1/2 ranged across the cohorts are as follows: 2.0–3.0 and 1.1–2.1 h. Plasma exposure, AUC0–? and Cmax, of CMX157 was dose-related. AUC0–? and Cmax ranges are 10.0–236 h ng/mL and 3.1–100 ng/mL across the ?ve cohorts. Data from the 5, 10, 25, and 50 mg cohorts in the HBV-infected subject study shows CMX157 was rapidly absorbed and eliminated as in the healthy volunteers. Corresponding tmax and t1/2 ranged across the cohorts are as follows: 2.0–2.5 and 1.0–1.3 h. Plasma exposure, AUC0–? and Cmax, of CMX157 was dose-related. AUC0–? and Cmax ranges are 2.3–112 h and 2.5–52.2 ng/mL across the four cohorts. CMX157 100 mg HBV-infected cohort, TFV and Viread safety, tolerability, pharmacokinetic parameters will also be presented.
Safety results, to date, show CMX157 was well tolerated with no serious adverse events (SAE), no discontinuations due to adverse events (AE), no dose-limiting toxicities or dose-dependence of adverse events. Overall, the incidence of adverse events and laboratory abnormalities was low and similar among cohorts. All AEs were mild. Dizziness and rhinorrhea were the most common.
Conclusion: CMX157 appeared to be safe and well tolerated in these studies. Consistent with a liver targeted approach, systemic exposure of parent drug and metabolite was low. The favorable safety pro?les, pharmacokinetic pro?les and in vitro anti-viral results warrant further clinical development of CMX157 in HBV-infected patients."
