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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

This study has been terminated.
(Business Objectives Have Changed)
Information provided by:
Bristol-Myers Squibb Identifier:
First received: January 18, 2008
Last updated: November 15, 2010
Last verified: November 2010
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.

Condition Intervention Phase
Chronic Hepatitis B
Drug: Entecavir + Tenofovir
Drug: Adefovir + continuing Lamivudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comparative Study of the Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Versus Adefovir Added to Continuing Lamivudine in Adults With Lamivudine- Resistant Chronic Hepatitis B Virus Infection

Resource links provided by NLM:

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48 [ Time Frame: Week 48 ]
    using the Roche COBAS® TaqMan HBV Test for use with the High Pure System (HPS) assay, by Polymerase Chain Reaction (PCR); HBV DNA < 50 IU/mL = approximately 300 copies/mL

Secondary Outcome Measures:
  • Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96 [ Time Frame: Week 96 ]
    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) ]
    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 ]
    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 ]
    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 ]
    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 ]
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL

Enrollment: 4
Study Start Date: August 2008
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Entecavir + Tenofovir
Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Other Name: Baraclude
Experimental: 2 Drug: Adefovir + continuing Lamivudine
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00605384

United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Kaiser Permanente Medical Center
San Francisco, California, United States, 94118
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, New York
Local Institution
New York, New York, United States, 10025
Local Institution
Bruxelles, Belgium, 1200
Local Institution
Leuven, Belgium, 3000
Local Institution
Berlin, Germany, 13353
Local Institution
Bonn, Germany, 53105
Local Institution
Duesseldorf, Germany, 40237
Local Institution
Mainz, Germany, 55131
Local Institution
Messina, Italy, 98124
Local Institution
Modena, Italy, 41100
Local Institution
Naples, Italy, 80135
Local Institution
Padova, Italy, 35128
Local Institution
San Giovanni Rotondo, Italy, 71013
Local Institution
Chorzow, Poland, 41-500
Local Institution
Krakow, Poland, 31-531
Local Institution
Lublin, Poland, 20-089
Local Institution
Ankara, Turkey, 06010
Local Institution
Ankara, Turkey, 06620
Local Institution
Istanbul, Turkey, 34093
Local Institution
Istanbul, Turkey, 34098
Local Institution
Istanbul, Turkey, 34360
Local Institution
Istanbul, Turkey, 34460
Local Institution
Istanbul, Turkey, 34722
Local Institution
Izmir, Turkey, 35100
Local Institution
Kocaeli, Turkey, 41380
Local Institution
Sihhiye Ankara, Turkey, 06100
Local Institution
Trabzon, Turkey, 61080
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Study Director, Bristol-Myers Squibb Identifier: NCT00605384     History of Changes
Other Study ID Numbers: AI463-137
Study First Received: January 18, 2008
Results First Received: July 13, 2010
Last Updated: November 15, 2010

Additional relevant MeSH terms:
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir dipivoxil
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents processed this record on May 24, 2017