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Suboptimal Responders to Adefovir Switching to Entecavir

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ClinicalTrials.gov Identifier: NCT00718887
Recruitment Status : Completed
First Posted : July 21, 2008
Results First Posted : February 11, 2013
Last Update Posted : February 11, 2013
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Entecavir Drug: Adefovir/Entecavir Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 228 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2008
Primary Completion Date : December 2009
Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Entecavir, 0.5 mg QD Drug: Entecavir
Tablets, Oral, 0.5 mg, once daily (QD), 52 weeks
Other Names:
  • Baraclude
  • BMS-200475
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Drug: Adefovir/Entecavir
Tablets, Oral, 10-mg adefovir QD for 12 weeks followed by 0.5-mg entecavir QD for a maximum of 52 weeks
Other Names:
  • Baraclude
  • BMS-200475

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing [ Time Frame: At Week 48 from Day 1 ]
    HBV=hepatitis B virus. HBV DNA Level <50 IU/mL=approximately 300 copies/mL.

  2. Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing [ Time Frame: At Weeks 12 and 48 from Day 1 ]
    HBV=hepatitis B virus

  3. Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT) [ Time Frame: At Weeks 12 and 48 from Day 1 ]
    ULN=upper limit of normal. ALT normalization= ≤1*ULN, among participants with baseline ALT >1*ULN

  4. Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion [ Time Frame: At Weeks 12 and 48 from Day 1 ]
  5. Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion [ Time Frame: At Weeks 12 and 48 from Day 1 ]
  6. Number of Participants With Genotypic Resistance to Entecavir [ Time Frame: At Week 48 from Day 1 ]
  7. 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 [ Time Frame: 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.

  8. Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results [ Time Frame: 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.

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00718887

China, Beijing
Local Institution
Beijing, Beijing, China, 100011
China, Guizhou
Local Institution
Guiyang, Guizhou, China, 550004
China, Jiangsu
Local Institution
Nanjing, Jiangsu, China, 210002
China, Jiangxi
Local Institution
Nanchang, Jiangxi, China, 330006
China, Jilin
Local Institution
Changchun, Jilin, China, 130021
China, Liaoning
Local Institution
Shenyang, Liaoning, China, 110004
China, Shanghai
Local Institution
Shanghai, Shanghai, China, 200235
Local Institution
Shanghai, Shanghai, China
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00718887     History of Changes
Other Study ID Numbers: AI463-171
First Posted: July 21, 2008    Key Record Dates
Results First Posted: February 11, 2013
Last Update Posted: February 11, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Hepatitis, Chronic
Adefovir dipivoxil
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents