Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection
- Registration Number
- NCT00096785
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
- Chronic hepatitis B treatment naive
- Compensated liver disease
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A1 entecavir - A2 adefovir -
- Primary Outcome Measures
Name Time Method Change From Baseline in Hepatitis B Virus DNA (HBV DNA) by Polymerase Chain Reaction (PCR) Assay at Week 12 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
Name Time Method Change From Baseline in HBV DNA by PCR Assay at Week 48 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) 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 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 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 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 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 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 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 Week 48 Laboratory abnormalities reported as clinical AEs
Trial Locations
- Locations (2)
Local Institution
🇹🇭Bankok, Thailand
Local Insitution
🇺🇸New York, New York, United States