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Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00096785
First Posted: November 16, 2004
Last Update Posted: August 10, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Bristol-Myers Squibb
  Purpose
The purpose of this study is to evaluate antiviral activity and efficacy of entecavir (ETV) compared to adefovir in adults with chronic hepatitis B who have not been treated yet with an antiviral medicine.

Condition Intervention Phase
Hepatitis B Chronic Disease Drug: entecavir Drug: adefovir Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Open-Label, Comparative Study to Evaluate Early Viral Load Reductions and Exploratory Viral Kinetics Following Administration of Entecavir or Adefovir in Nucleoside-Naive Adults With Chronic Hepatitis B Infection

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Change From Baseline in Hepatitis B Virus DNA (HBV DNA) by Polymerase Chain Reaction (PCR) Assay at Week 12 [ Time Frame: Baseline, Week 12 ]
    Antiviral efficacy, as measured by the mean reduction in serum HBV DNA levels by PCR (log10 copies/mL) at Week 12, adjusted for baseline (Week 12 - baseline). A negative value = improvement.


Secondary Outcome Measures:
  • Change From Baseline in HBV DNA by PCR Assay at Week 48 [ Time Frame: Baseline, Week 48 ]
    Antiviral efficacy, as measured by the mean reduction in serum HBV DNA levels by PCR (log10 copies/mL) at Week 48, adjusted for baseline (Week 48 - Baseline). A negative value = improvement.

  • Viral Load Undetectable (HBV DNA <300 Copies/mL) [ Time Frame: Week 48 ]
    Number of Subjects with HBV DNA <300 copies/mL by Roche COBAS® Amplicor (limit of quantitation 300 copies/mL)

  • Alanine Aminotransferase (ALT) Normalization [ Time Frame: Week 48 ]
    Number of participants with ALT ≤ 1 x upper limit of normal (ULN)

  • HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Efficacy in Blocking Virus Production and de Novo Infections [ Time Frame: Week 12 ]
    The biphasic decline of HBV DNA is characterized via a 4-parameter exponential decay model previously published for HBV compounds. The model parameters of interest are the effectiveness of the drug in blocking virus production from infected cells (efficacy, ε) and effectiveness of the study treatment in blocking de novo infection of susceptible cells (η). The model parameters reflect the biphasic pattern that is typically observed after initiation of antiviral therapy. Parameters were estimated for each subject separately and then averaged within each treatment group.

  • HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Viral Clearance Rate and Infected Cell Death Rate [ Time Frame: Week 12 ]
    The biphasic decline of HBV DNA is characterized via a 4-parameter exponential decay model previously published for HBV compounds. The model parameters of interest are the clearance rate of the free virus (c), the death rate of productively infected cells (δ), The model parameters reflect the biphasic pattern that is typically observed after initiation of antiviral therapy. Parameters were estimated for each subject separately and then averaged within each treatment group.

  • HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Half-Life of Free Virus [ Time Frame: Week 12 ]
    The biphasic decline of HBV DNA is characterized via a 4-parameter exponential decay model previously published for HBV compounds. An important derived parameter is the half-life of free virus (ie, the average amount of time for HBV particles in plasma to be reduced to half the initial level), calculated as 24*ln(2)/c. The model parameters reflect the biphasic pattern that is typically observed after initiation of antiviral therapy. Parameters were estimated for each subject separately and then averaged within each treatment group.

  • HBV DNA Viral Kinetics - Spline Model [ Time Frame: Week 12 ]
    This analysis uses a 3-parameter piece-wise linear model and describes the biphasic decline in HBV DNA (measured by PCR assay) through Week 12. The 3 parameters are the values for the 2 slopes, describing the first and second phase declines, respectively, and the estimated HBV DNA at the knot (at day 10; the time point where the 2 phases join). The biphasic viral decay kinetics for each treatment were obtained using a spline fitting procedure to estimate the 3 parameters for each subject; these estimates were then averaged within each treatment group.

  • Summary of Safety - Most Frequent (> 10%) Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Deaths [ Time Frame: cumulative through the end of on-treatment observation as available at the time of the Week 48 dataset ]
    AE=new untoward medical occurrence or worsening of pre-existing medical condition regardless of causal relationship to treatment. SAE=untoward medical occurrence that is life-threatening, a congenital anomaly/birth defect, or an important medical event, or results in death, inpatient hospitalization/prolongation of hospitalization, or persistent/significant disability. AE grades: mild (1), moderate (2), severe (3), life-threatening (4), death (5). ALT flare= >2x baseline & >10x ULN up to end of therapy + 5 days. Hepatic SAE=SAEs consistent with worsening of hepatitis or hepatic decompensation.

  • Summary of Safety - Laboratory Abnormalities Reported as Clinical AEs [ Time Frame: Week 48 ]
    Laboratory abnormalities reported as clinical AEs


Enrollment: 69
Study Start Date: December 2004
Study Completion Date: April 2008
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A1 Drug: entecavir
Tablets, Oral, ETV 0.5 mg, once daily, up to 96 weeks
Other Name: Baraclude
Active Comparator: A2 Drug: adefovir
Tablets, Oral, ADV 10 mg, once daily, up to 96 weeks

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic hepatitis B treatment naive
  • Compensated liver disease
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00096785


  Show 24 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00096785     History of Changes
Other Study ID Numbers: AI463-079
First Submitted: November 15, 2004
First Posted: November 16, 2004
Results First Submitted: July 2, 2009
Results First Posted: January 6, 2010
Last Update Posted: August 10, 2010
Last Verified: June 2010

Keywords provided by Bristol-Myers Squibb:
chronic hepatitis B infection

Additional relevant MeSH terms:
Infection
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Chronic Disease
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Disease Attributes
Pathologic Processes
Entecavir
Adefovir
Adefovir dipivoxil
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents