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

November 15, 2004
August 4, 2010
December 2004
January 2006   (final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00096785 on ClinicalTrials.gov Archive Site
  • 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
Not Provided
Not Provided
Not Provided
 
Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis B
  • Chronic Disease
  • Drug: entecavir
    Tablets, Oral, ETV 0.5 mg, once daily, up to 96 weeks
    Other Name: Baraclude
  • Drug: adefovir
    Tablets, Oral, ADV 10 mg, once daily, up to 96 weeks
  • Active Comparator: A1
    Intervention: Drug: entecavir
  • Active Comparator: A2
    Intervention: Drug: adefovir
Leung N, Peng CY, Hann HW, Sollano J, Lao-Tan J, Hsu CW, Lesmana L, Yuen MF, Jeffers L, Sherman M, Min A, Mencarini K, Diva U, Cross A, Wilber R, Lopez-Talavera J. Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients with chronic hepatitis B: A randomized international study of entecavir versus adefovir. Hepatology. 2009 Jan;49(1):72-9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
69
April 2008
January 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Chronic hepatitis B treatment naive
  • Compensated liver disease
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Thailand,   Canada,   Hong Kong,   Indonesia,   Philippines,   Singapore,   Taiwan
 
NCT00096785
AI463-079
No
Study Director, Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
June 2010

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