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

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00096785
• Other study ID #: AI463-079
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2004
• Last updated: August 4, 2010
• Start date: December 2004
• Est. completion date: April 2008

Study information

• Verified date: June 2010
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: April 2008
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Chronic hepatitis B treatment naive

• Compensated liver disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• entecavir
Tablets, Oral, ETV 0.5 mg, once daily, up to 96 weeks
• adefovir
Tablets, Oral, ADV 10 mg, once daily, up to 96 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Indonesia,  Philippines,  Singapore,  Taiwan,  Thailand, 

References & Publications (1)

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. doi: 10.1002/hep.22658. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hepatitis B Virus DNA (HBV DNA) by Polymerase Chain Reaction (PCR) Assay at 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	No
Secondary	Change From Baseline in HBV DNA by PCR Assay at 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	No
Secondary	Viral Load Undetectable (HBV DNA <300 Copies/mL)	Number of Subjects with HBV DNA <300 copies/mL by Roche COBAS® Amplicor (limit of quantitation 300 copies/mL)	Week 48	No
Secondary	Alanine Aminotransferase (ALT) Normalization	Number of participants with ALT = 1 x upper limit of normal (ULN)	Week 48	No
Secondary	HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Efficacy in Blocking Virus Production and de Novo Infections	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, e) and effectiveness of the study treatment in blocking de novo infection of susceptible cells (?). 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	No
Secondary	HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Viral Clearance Rate and Infected Cell Death Rate	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 (d), 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	No
Secondary	HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Half-Life of Free Virus	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	No
Secondary	HBV DNA Viral Kinetics - Spline Model	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	No
Secondary	Summary of Safety - Most Frequent (> 10%) Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Deaths	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	Yes
Secondary	Summary of Safety - Laboratory Abnormalities Reported as Clinical AEs	Laboratory abnormalities reported as clinical AEs	Week 48	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm