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A Phase IIIb Study to Compare Entecavir Plus Tenofovir vs. Adefovir Added to Continuing Lamivudine Therapy in Adult Patients With Lamivudine-Resistant Hepatitis B Infection

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ClinicalTrials.gov Identifier: NCT00605384
Recruitment Status : Terminated (Business Objectives Have Changed)
First Posted : January 31, 2008
Results First Posted : August 10, 2010
Last Update Posted : November 23, 2010
Sponsor:
Information provided by:
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Hepatitis B
Interventions Drug: Entecavir + Tenofovir
Drug: Adefovir + continuing Lamivudine
Enrollment 4
Recruitment Details A total of 84 subjects were to be treated with entecavir (ETV) plus tenofovir (TNF) or adefovir (ADV) added to continuing lamivudine (LVD).
Pre-assignment Details Of the 4 subjects enrolled, 2 were not randomized (reasons: “Subject no longer meets study criteria” and “Other”). Both subjects randomized were treated as well.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Period Title: Overall Study
Started 1 1
Completed 0 [1] 0 [1]
Not Completed 1 1
[1]
study terminated early
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine Total
Hide Arm/Group Description Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks Total of all reporting groups
Overall Number of Baseline Participants 1 1 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1 participants 1 participants 2 participants
Between 18 and 65 years 0 1 1
>=65 years 1 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 1 participants 2 participants
Female
1
 100.0%
0
   0.0%
1
  50.0%
Male
0
   0.0%
1
 100.0%
1
  50.0%
1.Primary Outcome
Title Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48
Hide Description using the Roche COBAS® TaqMan HBV Test for use with the High Pure System (HPS) assay, by Polymerase Chain Reaction (PCR); HBV DNA < 50 IU/mL = approximately 300 copies/mL
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96
Hide Description by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA < 50 IU/mL = approximately 300 copies/mL.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.
Time Frame Day 1 through end of treatment (Week 100 +/- 5 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants. Timeframe for Outcome Measure revised due to study termination. (Study Completion Date=February 2009).
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 1 1
Measure Type: Number
Unit of Measure: participants
AEs 1 1
SAEs 0 0
Deaths 0 0
Discontinuations due to AEs 0 0
Discontinuations due to Laboratory Abnormalities 0 0
4.Secondary Outcome
Title Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96
Hide Description by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title HBV DNA Values at Weeks 48 and 96
Hide Description Number of Participants with HBV DNA <LLD (4.8); LLD to <50; 50 to <172; 172 to <1,720; 1,720 to <17,200; and ≥17,200 IU/mL (<LLD (28); 28 to <300; 300 to <1,000; 1,000 to <10,000; 10,000 to <100,000; and ≥100,000 copies/mL by PCR, using the Roche COBAS®TaqMan - HPS assay
Time Frame Weeks 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96
Hide Description by PCR, using the Roche COBAS®TaqMan - HPS assay
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints was analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Number of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieved ALT Normalization (≤ 1 x ULN) at Weeks 48 and 96
Hide Description [Not Specified]
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96
Hide Description HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
Time Frame Baseline, Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints was analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96
Hide Description HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb)
Time Frame Baseline, Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96
Hide Description Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96
Hide Description Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAb = HBsAg antibodies. HBs Seroconversion = HBsAg loss and presence of HBseAb
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96
Hide Description HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL
Time Frame Week 48, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Due to early study termination, none of the efficacy endpoints were analyzed.
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description:
Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Hide Arm/Group Description Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
All-Cause Mortality
Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/1 (0.00%)   0/1 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Entecavir + Tenofovir Adefovir + Continuing Lamivudine
Affected / at Risk (%) Affected / at Risk (%)
Total   1/1 (100.00%)   1/1 (100.00%) 
Gastrointestinal disorders     
Hyperchlorhydria  1/1 (100.00%)  0/1 (0.00%) 
General disorders     
Fatigue  0/1 (0.00%)  1/1 (100.00%) 
Hepatobiliary disorders     
Hepatitis  0/1 (0.00%)  1/1 (100.00%) 
Following review of business priorities, BMS decided to terminate this study at an early stage. This was a strategic decision, not based on clinical or safety concerns. Due to limited data, no conclusions on safety and efficacy can be made.
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00605384     History of Changes
Other Study ID Numbers: AI463-137
First Submitted: January 18, 2008
First Posted: January 31, 2008
Results First Submitted: July 13, 2010
Results First Posted: August 10, 2010
Last Update Posted: November 23, 2010