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)
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00605384
First received: January 18, 2008
Last updated: November 15, 2010
Last verified: November 2010

January 18, 2008
November 15, 2010
August 2008
February 2009   (final data collection date for primary outcome measure)
Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
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
The proportion of subjects who achieve an HBV DNA level <50 IU/mL [ Time Frame: PCR at Week 48 of treatment ]
Complete list of historical versions of study NCT00605384 on ClinicalTrials.gov Archive Site
  • 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 proportion of subjects who achieve an HBV DNA level <50 IU/mL [ Time Frame: PCR at Week 96 of treatment ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis B
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
February 2009
February 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Germany,   Italy,   Poland,   Turkey
 
NCT00605384
AI463-137
No
Study Director, Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP