NCT00718887CompletedPhase 4
A Comparative Study of the Week 12 Antiviral Efficacy and Safety of Switching to Entecavir vs. Continuing Adefovir Treatment in Adults With Chronic Hepatitis B and Suboptimal Response to Adefovir
Bristol-Myers Squibb1 site in 1 country228 target enrollmentStarted: July 2008Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 228
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing
Study Overview
Brief Summary
Switching to Entecavir will result in superior antiviral efficacy as compared to continuing with Adefovir in patients with a suboptimal response to Adefovir
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Chronic infection with hepatitis B virus (HBV)(detectable hepatitis B surface antibody (HBsAg) at screening and at least 24 weeks prior to screening, or detectable HBsAg for <24 weeks and negative for immunoglobulin M core antibody)
- •Documentation of hepatitis B e antigen (HBeAg) positive or negative status
- •Naive to nucleoside/nucleotide analogues, with the exception of adefovir
- •Suboptimal response to adefovir treatment
- •No lamivudine/telbivudine, entecavir, or adefovir resistance-associated substitutions at screening
- •Male or female gender, aged 16 years and older
- •Compensated liver function
- •Serum alanine aminotransferase level <10*upper limit of normal at screening
Exclusion Criteria
- •Women who are pregnant or breastfeeding
- •Evidence of decompensated cirrhosis
- •Coinfection with HIV, hepatitis C virus, or hepatitis D virus
- •Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication)
- •Chronic renal insufficiency, defined as a creatinine clearance <50 mL/min
- •Current abuse of illegal drugs or alcohol, sufficient in the investigator's opinion to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis
- •Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications
- •Serum creatinine level >1.5 mg/dL; hemoglobin level <10.0 g/dL; platelet count <70,000/mm^3; absolute neutrophil count <1500 cells/mm^3; serum alpha fetoprotein level >100 ng/mL
- •Except adefovir, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (eg, lamivudine, entecavir), or any other experimental anti-HBV antiviral, or any China Traditional Medicine
- •Therapy with interferon, thymosin alpha, or other immunostimulators within 24 weeks of randomization
- •Required chronic administration of medications that cause immunosuppression, that are associated with a high risk of nephrotoxicity or hepatotoxicity, or that affect renal excretion.
Arms & Interventions
Entecavir, 0.5 mg QD
Experimental
Intervention: Entecavir (Drug)
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Other
Control
Intervention: Adefovir/Entecavir (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing
Time Frame: At Week 12 from Day 1
HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.
Secondary Outcomes
- Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing(At Week 48 from Day 1)
- Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion(At Weeks 12 and 48 from Day 1)
- Number of Participants With Genotypic Resistance to Entecavir(At Week 48 from Day 1)
- Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results(Day 1 through Week 48)
- Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)(At Weeks 12 and 48 from Day 1)
- Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing(At Weeks 12 and 48 from Day 1)
- Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation(Continually from Day 1 through Week 48, and through 24-week follow-up period)
- Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion(At Weeks 12 and 48 from Day 1)
Investigators
Study Sites (1)
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