A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B

Efficacy of TDF versus ADV will be evaluated for histologic improvement, reductions in serum
HBV DNA, changes in liver enzymes, and the generation of antibody to the virus. Safety will
be assessed by evaluating adverse events, laboratory abnormalities and the development of
drug-resistant mutations. After 48 weeks, all participants will receive open-label TDF, and
the efficacy and safety of TDF will be monitored for the remainder of the study.

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for
participation in this study:

- Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B
s-antigen (HBsAg) for more than 6 months

- 18 through 69 years of age, inclusive

- Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the
following:

- HBeAg positive at screening

- Alanine aminotransferase (ALT) levels > 2 × ULN and ≤ 10 × the upper limit of
the normal range (ULN)

- Serum HBV DNA > 1 million copies/mL at screening

- creatinine clearance ≥ 70 mL/min

- hemoglobin ≥ 8 g/dL

- neutrophils ≥ 1,000 /mL

- Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score < 4; however, up to
96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible
for enrollment

- Negative serum β-human chorionic gonadotropin (hCG)

- Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for > 12 weeks

- Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks

- Willing and able to provide written informed consent

- Liver biopsy performed within 6 months of baseline and has readable biopsy slides or
agrees to have a biopsy performed prior to baseline

Exclusion Criteria:

A patient who meets any of the following exclusion criteria is not to be enrolled in this
study:

- Pregnant women, women who are breast feeding or who believe they may wish to become
pregnant during the course of the study

- Males and females of reproductive potential who are unwilling to use an effective
method of contraception during the study; for males, condoms should be used and for
females, a barrier contraception method should be used

- Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin
time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior
history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy,
variceal hemorrhage)

- Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not)
therapy within 6 months prior to the pre-treatment biopsy

- Evidence of hepatocellular carcinoma (HCC), ie, α-fetoprotein >50 ng/mL

- Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or
hepatitis delta virus (HDV)

- Significant renal, cardiovascular, pulmonary, or neurological disease

- Received solid organ or bone marrow transplantation

- Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.),
investigational agents, nephrotoxic agents, or agents susceptible of modifying renal
excretion

- Has proximal tubulopathy