Clinical trial NCT00718887: Suboptimal Responders to Adefovir Switching to Entecavir
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B, Chronic
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-07-21
Enrollment: 228
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing
timeFrame: At Week 12 from Day 1
Secondary outcomes:
measure: Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing
timeFrame: At Week 48 from Day 1
measure: Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing
timeFrame: At Weeks 12 and 48 from Day 1
measure: Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)
timeFrame: At Weeks 12 and 48 from Day 1
measure: Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion
timeFrame: At Weeks 12 and 48 from Day 1
measure: Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
timeFrame: At Weeks 12 and 48 from Day 1
measure: Number of Participants With Genotypic Resistance to Entecavir
timeFrame: At Week 48 from Day 1
measure: 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
timeFrame: Continually from Day 1 through Week 48, and through 24-week follow-up period
measure: Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results
timeFrame: Day 1 through Week 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Guiyang
country: China
facility: Local Institution
state: Guizhou
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Nanchang
country: China
facility: Local Institution
state: Jiangxi
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Shenyang
country: China
facility: Local Institution
state: Liaoning
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: