title: 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.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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 log(10) 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 log(10) 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 log(10) reductions or more in HBV DNA level and resolved without dose interruption.
  
  
  CONCLUSIONS
  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.
authors: Michiko
authors: M
authors: Shindo
authors: Kazuaki
authors: K
authors: Chayama
authors: Satoshi
authors: S
authors: Mochida
authors: Joji
authors: J
authors: Toyota
authors: Eiichi
authors: E
authors: Tomita
authors: Hiromitsu
authors: H
authors: Kumada
authors: Osamu
authors: O
authors: Yokosuka
authors: Michio
authors: M
authors: Sata
authors: Norio
authors: N
authors: Hayashi
authors: Kazuyuki
authors: K
authors: Suzuki
authors: Takeshi
authors: T
authors: Okanoue
authors: Hirohito
authors: H
authors: Tsubouchi
authors: Hiroki
authors: H
authors: Ishikawa
authors: Taku
authors: T
authors: Seriu
authors: Masao
authors: M
authors: Omata