- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00096785
Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection
August 4, 2010 updated by: Bristol-Myers Squibb
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
69
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alberta
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Edmonton, Alberta, Canada
- Local Institution
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British Columbia
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Vancouver, British Columbia, Canada
- Local Institution
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Ontario
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Toronto, Ontario, Canada
- Local Institution
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Chai Wan, Hong Kong
- Local Institution
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Pokfulham, Hong Kong
- Local Institution
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Tai Po, Hong Kong
- Local Institution
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Jakarta, Indonesia
- Local Institution
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Cebu, Philippines
- Local Institution
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Manila, Philippines
- Local Institution
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Singapore, Singapore
- Local Institution
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Taichung, Taiwan
- Local Institution
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Taoyan, Taiwan
- Local Institution
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Bankok, Thailand
- Local Institution
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California
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San Diego, California, United States
- Local Institution
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San Francisco, California, United States
- Local Institution
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Torrance, California, United States
- Local Institution
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Florida
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Miami, Florida, United States
- Local Institution
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North Miami Beach, Florida, United States
- Local Institution
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Maryland
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Baltimore, Maryland, United States
- Local Institution
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New York
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New York, New York, United States
- Local Institution
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New York, New York, United States
- Local Insitution
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Pennsylvania
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Philadelphia, Pennsylvania, United States
- Local Institution
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Texas
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Dallas, Texas, United States
- Local Institution
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Galveston, Texas, United States
- Local Institution
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Chronic hepatitis B treatment naive
- Compensated liver disease
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: A1
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Tablets, Oral, ETV 0.5 mg, once daily, up to 96 weeks
Other Names:
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Active Comparator: A2
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Tablets, Oral, ADV 10 mg, once daily, up to 96 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Hepatitis B Virus DNA (HBV DNA) by Polymerase Chain Reaction (PCR) Assay at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in HBV DNA by PCR Assay at Week 48
Time Frame: Baseline, Week 48
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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.
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Baseline, Week 48
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Viral Load Undetectable (HBV DNA <300 Copies/mL)
Time Frame: Week 48
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Number of Subjects with HBV DNA <300 copies/mL by Roche COBAS® Amplicor (limit of quantitation 300 copies/mL)
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Week 48
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Alanine Aminotransferase (ALT) Normalization
Time Frame: Week 48
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Number of participants with ALT ≤ 1 x upper limit of normal (ULN)
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Week 48
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HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Efficacy in Blocking Virus Production and de Novo Infections
Time Frame: Week 12
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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.
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Week 12
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HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Viral Clearance Rate and Infected Cell Death Rate
Time Frame: Week 12
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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.
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Week 12
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HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Half-Life of Free Virus
Time Frame: Week 12
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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.
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Week 12
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HBV DNA Viral Kinetics - Spline Model
Time Frame: Week 12
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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.
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Week 12
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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
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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.
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cumulative through the end of on-treatment observation as available at the time of the Week 48 dataset
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Summary of Safety - Laboratory Abnormalities Reported as Clinical AEs
Time Frame: Week 48
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Laboratory abnormalities reported as clinical AEs
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Week 48
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2004
Primary Completion (Actual)
January 1, 2006
Study Completion (Actual)
April 1, 2008
Study Registration Dates
First Submitted
November 15, 2004
First Submitted That Met QC Criteria
November 15, 2004
First Posted (Estimate)
November 16, 2004
Study Record Updates
Last Update Posted (Estimate)
August 10, 2010
Last Update Submitted That Met QC Criteria
August 4, 2010
Last Verified
June 1, 2010
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Communicable Diseases
- Disease Attributes
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Chronic Disease
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Entecavir
- Adefovir
Other Study ID Numbers
- AI463-079
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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