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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

July 17, 2008
January 4, 2013
July 2008
December 2009   (final data collection date for primary outcome measure)
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.
Percent of HBV DNA < 50 IU/mL [ Time Frame: at Week 12 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00718887 on ClinicalTrials.gov Archive Site
  • 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.
  • Percent of HBV DNA < 50 IU/mL [ Time Frame: at Week 48 ] [ Designated as safety issue: No ]
  • Mean reduction of HBV DNA [ Time Frame: at Weeks 12 & 48 ] [ Designated as safety issue: No ]
  • Percentage of subjects with ALT normalization [ Time Frame: at Weeks 12 & 48 ] [ Designated as safety issue: No ]
  • Percentage of HBeAg loss, seroconversion, HBsAg loss and seroconversion [ Time Frame: at Weeks 12 & 48 ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
  • Resistance [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Suboptimal Responders to Adefovir Switching to Entecavir
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

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

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Hepatitis B, Chronic
  • Drug: Entecavir
    Tablets, Oral, 0.5 mg, once daily (QD), 52 weeks
    Other Names:
    • Baraclude
    • BMS-200475
  • 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
  • Experimental: Entecavir, 0.5 mg QD
    Intervention: Drug: Entecavir
  • Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
    Control
    Intervention: Drug: Adefovir/Entecavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
228
January 2011
December 2009   (final data collection date for primary outcome measure)

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.
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
China
 
NCT00718887
AI463-171
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP