Suboptimal Responders to Adefovir Switching to Entecavir

Phase 4

Completed

Conditions: Hepatitis B, Chronic

Interventions: Drug: Adefovir/Entecavir
Drug: Entecavir

Registration Number: NCT00718887

Lead Sponsor: Bristol-Myers Squibb

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 228

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD	Adefovir/Entecavir	Control
Entecavir, 0.5 mg QD	Entecavir	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing	At Week 12 from Day 1	HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.

Secondary Outcome Measures

Name	Time	Method
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	HBV=hepatitis B virus. HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.
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	Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.
Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)	At Weeks 12 and 48 from Day 1	ULN=upper limit of normal. ALT normalization= ≤1\ULN, among participants with baseline ALT \>1\ULN
Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing	At Weeks 12 and 48 from Day 1	HBV=hepatitis B virus
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	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study drug.
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion	At Weeks 12 and 48 from Day 1