Background & aims: Entecavir is a novel and selective nucleoside analogue with potent activity against hepatitis B virus (HBV).
Methods: In a 24-week, double-blind, randomized, multicenter, phase II clinical trial, the safety and efficacy of entecavir (0.01 mg/day, 0.1 mg/day, or 0.5 mg/day orally) were compared with lamivudine (100 mg/day orally). Patients (n = 169) chronically infected with HBV (hepatitis B e antigen [HBeAg]-positive and -negative) were evaluated for efficacy.
Results: Compared with lamivudine, entecavir reduced HBV DNA by an additional 0.97 log(10) at the 0.1-mg/day dose and an additional 1.28 log(10) at the 0.5-mg/day dose (P < 0.0001). A clear dose-response relationship was observed for entecavir with the higher doses showing significantly greater viral suppression. In patients treated with entecavir 0.5 mg/day, 83.7% had an HBV-DNA level below the lower limit of detection of the Quantiplex branched DNA (bDNA) assay (Bayer-Versant Diagnostics, formerly Chiron Diagnostics, Emeryville, CA), compared with 57.5% treated with 100 mg/day lamivudine (P = 0.008). In both treatment arms, very few patients achieved HBeAg loss and/or seroconversion by week 22. More patients treated with the 0.1-mg/day and 0.5-mg/day doses of entecavir had normalization of alanine transaminase (ALT) levels at week 22 compared with lamivudine (P = not significant). Entecavir was well tolerated; most adverse events were mild to moderate, transient, and comparable in all study arms.
Conclusions: This study showed that entecavir has potent antiviral activity against HBV at 0.1-mg/day and 0.5-mg/day doses, both of which were superior to lamivudine in chronically infected HBV patients.