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Suboptimal Responders to Adefovir Switching to Entecavir

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Entecavir
Adefovir/Entecavir
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Entecavir, 0.5 mg QD

Adefovir, 10 mg QD/Entecavir, 0.5 mg QD

Arm Description

Control

Outcomes

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
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
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
HBV=hepatitis B virus
Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)
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
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
Number of Participants With Genotypic Resistance to Entecavir
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
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
Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.

Full Information

First Posted
July 17, 2008
Last Updated
January 4, 2013
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00718887
Brief Title
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

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
228 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Entecavir, 0.5 mg QD
Arm Type
Experimental
Arm Title
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Arm Type
Other
Arm Description
Control
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude, BMS-200475
Intervention Description
Tablets, Oral, 0.5 mg, once daily (QD), 52 weeks
Intervention Type
Drug
Intervention Name(s)
Adefovir/Entecavir
Other Intervention Name(s)
Baraclude, BMS-200475
Intervention Description
Tablets, Oral, 10-mg adefovir QD for 12 weeks followed by 0.5-mg entecavir QD for a maximum of 52 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing
Description
HBV DNA Level <50 IU/mL=approximately 300 copies/mL.
Time Frame
At Week 12 from Day 1
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing
Description
HBV=hepatitis B virus. HBV DNA Level <50 IU/mL=approximately 300 copies/mL.
Time Frame
At Week 48 from Day 1
Title
Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing
Description
HBV=hepatitis B virus
Time Frame
At Weeks 12 and 48 from Day 1
Title
Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)
Description
ULN=upper limit of normal. ALT normalization= ≤1*ULN, among participants with baseline ALT >1*ULN
Time Frame
At Weeks 12 and 48 from Day 1
Title
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
Title
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
Time Frame
At Weeks 12 and 48 from Day 1
Title
Number of Participants With Genotypic Resistance to Entecavir
Time Frame
At Week 48 from Day 1
Title
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
Description
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.
Time Frame
Continually from Day 1 through Week 48, and through 24-week follow-up period
Title
Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results
Description
Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.
Time Frame
Day 1 through Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100011
Country
China
Facility Name
Local Institution
City
Guiyang
State/Province
Guizhou
ZIP/Postal Code
550004
Country
China
Facility Name
Local Institution
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
Facility Name
Local Institution
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Facility Name
Local Institution
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Local Institution
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110004
Country
China
Facility Name
Local Institution
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200235
Country
China
Facility Name
Local Institution
City
Shanghai
State/Province
Shanghai
Country
China

12. IPD Sharing Statement

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Suboptimal Responders to Adefovir Switching to Entecavir

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