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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00096785
First received: November 15, 2004
Last updated: August 4, 2010
Last verified: June 2010
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic hepatitis B treatment naive
  • Compensated liver disease
  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 ClinicalTrials.gov identifier: NCT00096785

  Hide Study Locations
Locations
United States, California
Local Institution
San Diego, California, United States
Local Institution
San Francisco, California, United States
Local Institution
Torrance, California, United States
United States, Florida
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Miami, Florida, United States
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North Miami Beach, Florida, United States
United States, Maryland
Local Institution
Baltimore, Maryland, United States
United States, New York
Local Insitution
New York, New York, United States
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New York, New York, United States
United States, Pennsylvania
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Philadelphia, Pennsylvania, United States
United States, Texas
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Dallas, Texas, United States
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Galveston, Texas, United States
Canada, Alberta
Local Institution
Edmonton, Alberta, Canada
Canada, British Columbia
Local Institution
Vancouver, British Columbia, Canada
Canada, Ontario
Local Institution
Toronto, Ontario, Canada
Hong Kong
Local Institution
Chai Wan, Hong Kong
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Pokfulham, Hong Kong
Local Institution
Tai Po, Hong Kong
Indonesia
Local Institution
Jakarta, Indonesia
Philippines
Local Institution
Cebu, Philippines
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Manila, Philippines
Singapore
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Singapore, Singapore
Taiwan
Local Institution
Taichung, Taiwan
Local Institution
Taoyan, Taiwan
Thailand
Local Institution
Bankok, Thailand
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
Study First Received: November 15, 2004
Results First Received: July 2, 2009
Last Updated: August 4, 2010
Health Authority: United States: Food and Drug Administration

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
Adefovir
Adefovir dipivoxil
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on October 19, 2014