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Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00410072
First received: December 11, 2006
Last updated: March 13, 2013
Last verified: March 2013
History of Changes
Results First Received: November 4, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hepatitis B, Chronic
Interventions: Drug: Entecavir
Drug: Entecavir + Tenofovir

  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
669 participants were enrolled; 384 were randomized. Among 285 who were not randomized, 266 did not meet the study criteria, 11 other, 1 poor compliance/noncompliance, 4 lost to follow-up, 1 withdrew consent, and 2 for administrative reasons.

Reporting Groups
  Description
ETV 0.5 mg Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks
ETV 0.5 mg +TDF 300 mg ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks

Participant Flow for 2 periods

 Period 1:   Day 1 to Week 48
    ETV 0.5 mg     ETV 0.5 mg +TDF 300 mg  
STARTED     182 [1]   197 [2]
COMPLETED     176     185  
NOT COMPLETED     6     12  
Adverse Event                 1                 2  
Lost to Follow-up                 5                 2  
Not specified                 0                 1  
poor compliance/noncompliance                 0                 3  
Pregnancy                 0                 2  
Withdrawal by Subject                 0                 2  
[1] Number of participants randomized and treated; 4 more were randomized but not treated.
[2] Number of participants randomized and treated; 1 more was randomized but not treated.

Period 2:   After Week 48 to Week 96
    ETV 0.5 mg     ETV 0.5 mg +TDF 300 mg  
STARTED     176     185  
COMPLETED     170     174  
NOT COMPLETED     6     11  
Adverse Event                 1                 2  
Death                 0                 1  
Lack of Efficacy                 1                 0  
Lost to Follow-up                 2                 4  
Not specified                 2                 0  
Poor compliance/noncompliance                 0                 1  
Pregnancy                 0                 2  
Withdrawal by Subject                 0                 1  



  Baseline Characteristics
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Reporting Groups
  Description
ETV 0.5 mg Entecavir (ETV) 0.5 mg monotherapy given once daily (QD) for 100 weeks
ETV 0.5 mg +TDF 300 mg ETV 0.5 mg plus Tenofovir (TDF) 300 mg combination therapy given QD for 100 weeks
Total Total of all reporting groups

Baseline Measures
    ETV 0.5 mg     ETV 0.5 mg +TDF 300 mg     Total  
Number of Participants  
[units: participants]
 		  182     197     379  
Age, Customized  
[units: Participants]
 		     
16 - 20 years     13     19     32  
21 - 64 years     157     169     326  
>=65 years     12     9     21  
Gender  
[units: participants]
 		     
Female     66     51     117  
Male     116     146     262  
Race/Ethnicity, Customized  
[units: Participants]
 		     
Asian     84     102     186  
Black/African American     10     4     14  
Native Hawaiian/Other Pacific Islander     1     1     2  
White     83     87     170  
Other     4     3     7  
Country  
[units: participants]
 		     
United States     35     43     78  
Turkey     11     11     22  
Russian Federation     24     23     47  
Italy     12     15     27  
India     5     9     14  
France     8     5     13  
Canada     29     33     62  
Argentina     12     15     27  
Poland     15     13     28  
Brazil     5     3     8  
Australia     24     24     48  
South Africa     2     3     5  
Region  
[units: Participants]
 		     
Africa     2     3     5  
Asia     29     33     62  
Europe     70     67     137  
North America     64     76     140  
South America     17     18     35  
Hepatitis B e antibody (HBeAb) at baseline  
[units: Participants]
 		     
Positive     60     60     120  
Negative     122     137     259  
Hepatitis B e antigen (HBeAg) status at baseline  
[units: Participants]
 		     
Positive (> 172,000 IU/mL; approx 10^6 copies/mL)     126     138     264  
Negative (> 17,200 IU/mL; approx 10^5 copies/mL)     56     59     115  
Hepatitis B surface antigen (HBsAg) status at baseline  
[units: Participants]
 		     
Positive     182     196     378  
Negative     0     1     1  



  Outcome Measures
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1.  Primary:   Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96   [ Time Frame: At Week 96 ]
  Show Outcome Measure 1

2.  Secondary:   Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 2

3.  Secondary:   Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 3

4.  Secondary:   Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 4

5.  Secondary:   Mean Log 10 HBV DNA at Weeks 48 and 96   [ Time Frame: Baseline, Weeks 48 and 96 ]
  Show Outcome Measure 5

6.  Secondary:   Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 6

7.  Secondary:   Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 7

8.  Secondary:   Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 8

9.  Secondary:   Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 9

10.  Secondary:   Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 10

11.  Secondary:   Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 ]
  Show Outcome Measure 11

12.  Secondary:   Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities   [ Time Frame: From enrollment through Week 100 + 24-week follow-up ]
  Show Outcome Measure 12

13.  Secondary:   Number of Participants With HBV Resistance Through Week 48   [ Time Frame: Week 48 ]
  Show Outcome Measure 13

14.  Secondary:   Number of Participants With HBV Resistance at Week 96   [ Time Frame: Week 96 ]
  Show Outcome Measure 14

15.  Secondary:   Number of Participants With Virologic Breakthrough at Week 48   [ Time Frame: Week 48 ]
  Show Outcome Measure 15

16.  Secondary:   Number of Participants With Virologic Breakthrough at Week 96   [ Time Frame: Week 96 ]
  Show Outcome Measure 16


  Serious Adverse Events
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  Other Adverse Events
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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.


Limitations and Caveats
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
No text entered.  


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


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00410072     History of Changes
Other Study ID Numbers: AI463-110
Study First Received: December 11, 2006
Results First Received: November 4, 2011
Last Updated: March 13, 2013
Health Authority: United States: Food and Drug Administration