Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00096785
First received: November 15, 2004
Last updated: August 4, 2010
Last verified: June 2010
Results First Received: July 2, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Hepatitis B
Chronic Disease
Interventions: Drug: entecavir
Drug: adefovir

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
132 enrolled; 63 not randomized (59 did not meet study criteria, 3 withdrew consent, 1 lost to follow-up). 1 randomized to adefovir (ADV) received entecavir (ETV) throughout treatment, & is counted in the ADV group for primary efficacy analysis, not included in the secondary efficacy analyses, & counted in the ETV group in safety analyses.

Reporting Groups
  Description
Entecavir ETV 0.5 mg once daily (QD)
Adefovir ADV 10 mg QD

Participant Flow:   Overall Study
    Entecavir     Adefovir  
STARTED     35 [1]   34 [2]
As-Randomized Population     35     34  
As-Treated Population     36     33  
COMPLETED     33 [3]   33 [3]
NOT COMPLETED     2     1  
Lost to Follow-up                 1                 0  
Withdrawal by Subject                 0                 1  
Relocated                 1                 0  
[1] 1 participant randomized to ADV, treated with ETV. (As randomized= 35; as treated=36)
[2] 1 participant randomized to ADV, treated with ETV. (As randomized= 34; as treated=33)
[3] As randomized cohort



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Entecavir ETV 0.5 mg once daily (QD)
Adefovir ADV 10 mg QD
Total Total of all reporting groups

Baseline Measures
    Entecavir     Adefovir     Total  
Number of Participants  
[units: participants]
  35     34     69  
Age  
[units: years]
Mean ± Standard Deviation
  37  ± 2.3     32  ± 1.9     34  ± 1.5  
Age  
[units: participants]
Median ( Full Range )
  38  
  ( 18 to 76 )  
  28  
  ( 17 to 57 )  
  31  
  ( 17 to 76 )  
Gender  
[units: participants]
     
Female     13     11     24  
Male     22     23     45  
Race/Ethnicity, Customized  
[units: Participants]
     
Asian     31     30     61  
Native Hawaiian or Other Pacific Islander     0     1     1  
Black or African American     3     2     5  
White     1     1     2  
Region of Enrollment  
[units: participants]
     
North America     9     13     22  
East Asia     26     21     47  
Prior interferon (IFN)  
[units: Participants]
     
Prior IFN     1     1     2  
No prior IFN     34     33     67  
Alanine Aminotransferease (ALT)  
[units: U/L]
Mean ± Standard Deviation
  109.4  ± 81.76     176.4  ± 207.22     142.4  ± 159.12  
Hepatitis B virus DNA (HBV DNA) by Polymerase Chain Reaction (PCR)  
[units: log10┬ácopies/mL]
Mean ± Standard Deviation
  10.45  ± 2.125     9.89  ± 1.201     10.18  ± 1.742  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Hepatitis B Virus DNA (HBV DNA) by Polymerase Chain Reaction (PCR) Assay at Week 12   [ Time Frame: Baseline, Week 12 ]

2.  Secondary:   Change From Baseline in HBV DNA by PCR Assay at Week 48   [ Time Frame: Baseline, Week 48 ]

3.  Secondary:   Viral Load Undetectable (HBV DNA <300 Copies/mL)   [ Time Frame: Week 48 ]

4.  Secondary:   Alanine Aminotransferase (ALT) Normalization   [ Time Frame: Week 48 ]

5.  Secondary:   HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Efficacy in Blocking Virus Production and de Novo Infections   [ Time Frame: Week 12 ]

6.  Secondary:   HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Viral Clearance Rate and Infected Cell Death Rate   [ Time Frame: Week 12 ]

7.  Secondary:   HBV DNA Viral Kinetics Estimates of Exponential Decay Model - Half-Life of Free Virus   [ Time Frame: Week 12 ]

8.  Secondary:   HBV DNA Viral Kinetics - Spline Model   [ Time Frame: Week 12 ]

9.  Secondary:   Summary of Safety - Most Frequent (> 10%) Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Deaths   [ Time Frame: cumulative through the end of on-treatment observation as available at the time of the Week 48 dataset ]

10.  Secondary:   Summary of Safety - Laboratory Abnormalities Reported as Clinical AEs   [ Time Frame: Week 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


Publications:

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00096785     History of Changes
Other Study ID Numbers: AI463-079
Study First Received: November 15, 2004
Results First Received: July 2, 2009
Last Updated: August 4, 2010
Health Authority: United States: Food and Drug Administration