Antiviral activity, dose–response relationship, and safety of entecavir following 24-week oral dosing in nucleoside-naive Japanese adult patients with chronic hepatitis B: a randomized, double-blind, phase II clinical trial
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A randomized, double-blind, multicenter study (ETV-047) was conducted to evaluate the dose–response relationship of entecavir and compare its antiviral activity and safety with lamivudine in Japanese patients with chronic hepatitis B (CHB).
One hundred thirty-seven nucleoside-naive adult patients with CHB were randomized to once-daily oral doses of entecavir 0.01, 0.1, or 0.5 mg or lamivudine 100 mg for 24 weeks. The primary efficacy end point used to evaluate the dose–response relationship was mean change from baseline in serum hepatitis B virus (HBV) DNA level at week 22, as determined by polymerase chain reaction assay.
Entecavir demonstrated a clear dose–response relationship, with mean change from baseline in serum HBV DNA level of −3.11, −4.77, and −5.16 log10 copies/ml with entecavir 0.01, 0.1, and 0.5 mg, respectively. Entecavir 0.5 mg was superior to lamivudine 100 mg for the mean change in HBV DNA level (−5.16 vs. −4.29 log10 copies/ml; P = 0.007). The overall incidence of adverse events was comparable between treatment groups. Two patients discontinued treatment because of adverse events (one with liver cirrhosis [entecavir 0.5 mg] and one with grade 4 serum alanine aminotransferase (ALT) elevation, nausea, and malaise [lamivudine 100 mg]). Serum ALT flares were observed in four patients; flares were associated with 2 log10 reductions or more in HBV DNA level and resolved without dose interruption.
Entecavir 0.01–0.5 mg is well tolerated and produces a dose-dependent reduction in viral load in nucleoside-naive Japanese patients with CHB. Compared with lamivudine 100 mg, entecavir 0.1 mg demonstrated noninferiority and entecavir 0.5 mg was superior in this population.
KeywordsChronic hepatitis B Entecavir Lamivudine HBV DNA ALT flare
- 1.Maddrey WC. Hepatitis B: an important public health issue. J Med Virol 2000;61:362–366. doi: 10.1002/1096-9071(200007)61:3<362::AID-JMV14>3.0.CO;2-I PubMedCrossRefGoogle Scholar
- 2.Kao JH, Chen DS. The natural history of hepatitis B virus infection. In Lai CL, Locarnini S, editors. Hepatitis B Virus. London: International Medical Press; 2002. 161–172Google Scholar
- 6.Allen MI, Deslauriers M, Andrews CW, Tipples GA, Walters KA, Tyrrell DL, et al. Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group. Hepatology 1998;27:1670–1677. doi: 10.1002/hep.510270628 PubMedCrossRefGoogle Scholar
- 19.Tenney DJ, Levine SM, Rose RE, Walsh AW, Weinheimer SP, Discotto L, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chemother 2004;48:3498–3507. doi: 10.1128/AAC.48.9.3498-3507.2004 PubMedCrossRefGoogle Scholar