Suboptimal Responders to Adefovir Switching to Entecavir

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00718887
First received: July 17, 2008
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

Switching to Entecavir will result in superior antiviral efficacy as compared to continuing with Adefovir in patients with a suboptimal response to Adefovir


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    HBV DNA Level <50 IU/mL=approximately 300 copies/mL.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    HBV=hepatitis B virus. HBV DNA Level <50 IU/mL=approximately 300 copies/mL.

  • 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 ] [ Designated as safety issue: No ]
    HBV=hepatitis B virus

  • Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT) [ Time Frame: At Weeks 12 and 48 from Day 1 ] [ Designated as safety issue: No ]
    ULN=upper limit of normal. ALT normalization= ≤1*ULN, among participants with baseline ALT >1*ULN

  • 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 ] [ Designated as safety issue: No ]
  • Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion [ Time Frame: At Weeks 12 and 48 from Day 1 ] [ Designated as safety issue: No ]
  • Number of Participants With Genotypic Resistance to Entecavir [ Time Frame: At Week 48 from Day 1 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results [ Time Frame: Day 1 through Week 48 ] [ Designated as safety issue: Yes ]
    Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.


Enrollment: 228
Study Start Date: July 2008
Study Completion Date: January 2011
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Control
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

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00718887

Locations
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
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00718887     History of Changes
Other Study ID Numbers: AI463-171
Study First Received: July 17, 2008
Results First Received: October 17, 2012
Last Updated: January 4, 2013
Health Authority: China: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 28, 2014