Comparison of the Efficacy and Safety of Entecavir Versus Adefovir in Subjects Chronically Infected With Hepatitis B Virus and Evidence of Hepatic Decompensation

Bristol-Myers Squibb19 sites in 3 countries195 target enrollmentAugust 2003

ConditionsHepatitis B

InterventionsEntecavir (ETV)Adefovir (ADV)

DrugsEntecavir (ETV)Adefovir (ADV)

Overview

Phase: Phase 3
Intervention: Entecavir (ETV)
Conditions: Hepatitis B
Sponsor: Bristol-Myers Squibb
Enrollment: 195
Locations: 19
Primary Endpoint: Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase IIIb comparative study of entecavir 1.0 mg once daily (QD) vs. adefovir 10 mg QD in patients who have chronic hepatitis B infection and hepatic decompensation. The patients are treated for 96 weeks after the last subject is randomized.

Registry

clinicaltrials.gov

Start Date

August 2003

End Date

May 2013

Last Updated

12 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arms & Interventions

A1

Intervention: Entecavir (ETV)

A2

Intervention: Adefovir (ADV)

Outcomes

Primary Outcomes

Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24

Time Frame: Baseline, Week 24

Mean reduction in serum HBV DNA determined by PCR assay (log10 copies/mL) at Week 24 adjusted for baseline HBV DNA and lamivudine resistance (LVDr) status, based on linear regression analysis.

Secondary Outcomes

Change From Baseline in HBV DNA by PCR at Week 48(Baseline, Week 48)
Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24(Week 24)
Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48(Week 48)
Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48(Week 24, Week 48)
Number of Subjects Achieving Composite Endpoint (HBV DNA < 10*4 Copies/mL by PCR Assay and Normal ALT [≤ 1.0 x ULN]) Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 48)
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 48)
Change From Baseline in Child-Pugh Score Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48(Week 24, Week 48)
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Improvement or No Worsening in MELD Score Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 48)
Mean Changes From Baseline in Quality of Life as Measured by the Short Form 36 (SF-36)(Baseline, Week 24, Week 48)
Mean Changes From Baseline in Quality of Life, as Measured by EuroQol-5D (EQ-5D) at Weeks 24 and 48(Baseline, Week 24, Week 48)
Change From Baseline in Albumin Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Mean Change From Baseline in Prothrombin Time Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Mean Change From Baseline in Total Bilirubin Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Change From Baseline in Platelet Count Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Participants Achieving Albumin Normalization Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Participants Achieving Prothrombin Time Normalization Through Week 48(Baseline, Week4, Week 8, Week 12, Week 24, Week 36, Week 48)
Participants Achieving Total Bilirubin Normalization Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Participants Achieving Platelet Count Normalization Through Week 48(Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48)
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48(Week 48)
Cumulative Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, HCC, Discontinuations Due to AEs, and Confirmed Creatinine Increase >=0.5 mg/dL(on-treatment events obtained after the start of therapy and no more than 5 days after the last dose of study therapy.)
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data(Week 48=all on-treatment laboratory measurements up to Week 48. Cumulative data = on-treatment laboratory measurements obtained after the start of therapy and no more than 5 days after the last dose of study therapy.)
Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment(On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date.)
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period(On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.)
Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up(On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.)