A Phase IIIb Study to Compare Entecavir Plus Tenofovir vs. Adefovir Added to Continuing Lamivudine Therapy in Adult Patients With Lamivudine-Resistant Hepatitis B Infection

• Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA < 50 IU/mL = approximately 300 copies/mL.
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities [ Time Frame: Day 1 through end of treatment (Week 100 +/- 5 days) ] [ Designated as safety issue: Yes ]
  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.
• Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
  by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)
• HBV DNA Values at Weeks 48 and 96 [ Time Frame: Weeks 48, Week 96 ] [ Designated as safety issue: No ]
  Number of Participants with HBV DNA <LLD (4.8); LLD to <50; 50 to <172; 172 to <1,720; 1,720 to <17,200; and ≥17,200 IU/mL (<LLD (28); 28 to <300; 300 to <1,000; 1,000 to <10,000; 10,000 to <100,000; and ≥100,000 copies/mL by PCR, using the Roche COBAS®TaqMan - HPS assay
• Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
  by PCR, using the Roche COBAS®TaqMan - HPS assay
• Number of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieved ALT Normalization (≤ 1 x ULN) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
• Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
• Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb)
• Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
  Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection
• Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
  Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAb = HBsAg antibodies. HBs Seroconversion = HBsAg loss and presence of HBseAb
• Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
  HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL

The purpose of this clinical research study is to find out whether a combination of entecavir (ETV) plus tenofovir (TNF) works better against Hepatitis B virus than adefovir (ADV) added to continuing lamivudine (LVD) therapy in patients whose Hepatitis B virus (HBV) is resistant against lamivudine. The safety of this treatment will also be studied.

• Drug: Entecavir + Tenofovir
  Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
  Other Name: Baraclude
• Drug: Adefovir + continuing Lamivudine
  Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks

• Experimental: 1
  Intervention: Drug: Entecavir + Tenofovir
• Experimental: 2
  Intervention: Drug: Adefovir + continuing Lamivudine

Inclusion Criteria:

• Chronic HBV infection
• History of lamivudine (LVD) treatment, and lamivudine resistance (LVDr), receiving LVD at screening visit
• Compensated liver function
• HBV DNA ≥ 172,000 IU/mL
• Hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative

Exclusion Criteria:

• Evidence of decompensated cirrhosis
• Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
• Recent history of pancreatitis
• Serum alpha fetoprotein > 100 ng/mL
• Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B