A Efficacy and Safety Study of Adefovir Dipivoxil to Treat Chinese Patients With HBeAg+ve Chronic Hepatitis B

• The proportion of subjects with ALT normalisation [ Time Frame: Week 52, 104, 156, 208, 260 ]
• log10 reduction in serum HBV DNA [ Time Frame: Week 52, 104, 156, 208, 260 ]
• The proportion of subjects with HBV DNA 10(5) copies/mL or a 2 log10 reduction from Baseline HBV DNA level [ Time Frame: Week 52, 104, 156, 208, 260 ]
• The proportion of subjects with HBeAg loss [ Time Frame: Week 52, 104, 156, 208, 260 ]
• The proportion of subjects with HBeAg seroconversion [ Time Frame: Week 52, 104, 156, 208, 260 ]
• The proportion of subjects developing N236T and A181V HBV DNA genotypic mutations associated with ADV resistance [ Time Frame: Week 52, 104, 156, 208, 260 ]
• The proportion of subjects with HBV DNA undetectable (<300 copies/mL) [ Time Frame: Week 52, 104, 156, 208, 260 ]

The purpose of this study is to determine whether Adefovir Dipivoxil is effective and safe in treatment of Chinese Patients with HBeAg positive Chronic Hepatitis B for 5 years.

• Drug: AAAA
  Adefovir Dipivoxil (12 weeks) + open lable Adefovir Dipivoxil (28 weeks) + Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (52-260weeks)
• Drug: AAPA
  Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (28 weeks) + placebo (12 weeks) + open label-Adefovir Dipivoxil (52-260 weeks)
• Drug: PAAA
  Placebo (12 weeks) + Open label Adefovir Dipivoxil (28 weeks) + Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (52-260 weeks)

• Experimental: Adefovir Dipivoxil
  ADV 10mg tablets once daily
  Interventions:

  • Drug: AAAA
  • Drug: AAPA
  • Drug: PAAA
• Placebo Comparator: Adefovir Dipivoxil matched placebo
  Adefovir Dipivoxil matched placebo one tablet once daily
  Interventions:

  • Drug: AAPA
  • Drug: PAAA

Inclusion Criteria:

• Aged 18-65 years
• Presence of HBsAg and HBeAg at the time of screening and for at least 6 months prior to screening.
• Positive HBV DNA plasma assay with screening value equal or more than 10 (6) copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD less than 300 copies/mL) at the time of screening (within 4 weeks of randomisation).
• Evidence of elevated serum ALT levels defined as serum ALT level greater than or equal to 2.0 times (inclusive) the upper limit of the normal range (ULN) in the previous 6 months, and serum ALT levels greater than 1.0 times the ULN at the time of screening.

Exclusion Criteria:

• Evidence of hepatocellular carcinoma;
• Clinical signs of liver decompensation;
• Serum creatinine more than 1.5 mg/dL;
• ALT more than 10 x ULN; seropositivity for hepatitis C or D virus or HIV;
• Lamivudine therapy within 3 months prior to screening;
• ADV therapy or any other anti-HBV therapy within the previous 6 months;
• Use of systemic antiviral agents, immunomodulators, immunosuppressive therapy, Chinese Traditional Medicines or agents known to lower ALT levels during the study.