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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • Local Institution
    • British Columbia
      • Vancouver, British Columbia, Canada
        • Local Institution
    • Ontario
      • Toronto, Ontario, Canada
        • Local Institution
  • Hong Kong
      • Chai Wan, Hong Kong
        • Local Institution
      • Pokfulham, Hong Kong
        • Local Institution
      • Tai Po, Hong Kong
        • Local Institution
  • Indonesia
      • Jakarta, Indonesia
        • Local Institution
  • Philippines
      • Cebu, Philippines
        • Local Institution
      • Manila, Philippines
        • Local Institution
  • Singapore
      • Singapore, Singapore
        • Local Institution
  • Taiwan
      • Taichung, Taiwan
        • Local Institution
      • Taoyan, Taiwan
        • Local Institution
  • Thailand
      • Bankok, Thailand
        • Local Institution
  • United States
    • California
      • San Diego, California, United States
        • Local Institution
      • San Francisco, California, United States
        • Local Institution
      • Torrance, California, United States
        • Local Institution
    • Florida
      • Miami, Florida, United States
        • Local Institution
      • North Miami Beach, Florida, United States
        • Local Institution
    • Maryland
      • Baltimore, Maryland, United States
        • Local Institution
    • New York
      • New York, New York, United States
        • Local Institution
      • New York, New York, United States
        • Local Insitution
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Local Institution
    • Texas
      • Dallas, Texas, United States
        • Local Institution
      • Galveston, Texas, United States
        • Local Institution

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: A1
Drug: entecavir
Tablets, Oral, ETV 0.5 mg, once daily, up to 96 weeks
Other Names:
  • Baraclude
Active Comparator: A2
Drug: adefovir
Tablets, Oral, ADV 10 mg, once daily, up to 96 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 48
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)
Week 48
Alanine Aminotransferase (ALT) Normalization
Time Frame: Week 48
Number of participants with ALT ≤ 1 x upper limit of normal (ULN)
Week 48
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
cumulative through the end of on-treatment observation as available at the time of the Week 48 dataset
Summary of Safety - Laboratory Abnormalities Reported as Clinical AEs
Time Frame: Week 48
Laboratory abnormalities reported as clinical AEs
Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

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.

General Publications

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2006

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 15, 2004

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2004

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 16, 2004

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2010

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2010

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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