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Business Objectives Have Changed
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The purpose of this clinical research study is to find out whether a combination of entecavir (ETV) plus tenofovir (TNF) works better against Hepatitis B virus than adefovir (ADV) added to continuing lamivudine (LVD) therapy in patients whose Hepatitis B virus (HBV) is resistant against lamivudine. The safety of this treatment will also be studied.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
| |
| 2 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entecavir + Tenofovir | Drug | Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48 | 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 | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96 | by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA < 50 IU/mL = approximately 300 copies/mL. | Week 96 |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars Sinai Medical Center | Los Angeles | California | 90048 | United States | ||
| Kaiser Permanente Medical Center |
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.
A total of 84 subjects were to be treated with entecavir (ETV) plus tenofovir (TNF) or adefovir (ADV) added to continuing lamivudine (LVD).
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| ID | Title | Description |
|---|---|---|
| FG000 | Entecavir + Tenofovir | Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks |
| FG001 | Adefovir + Continuing Lamivudine | Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Adefovir + continuing Lamivudine | Drug | Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks |
|
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. |
| Day 1 through end of treatment (Week 100 +/- 5 days) |
| Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96 | by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL) | Week 48, Week 96 |
| HBV DNA Values at Weeks 48 and 96 | Number of Participants with HBV DNA \ | Weeks 48, Week 96 |
| Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96 | by PCR, using the Roche COBAS®TaqMan - HPS assay | Week 48, Week 96 |
| 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 | Week 48, Week 96 |
| Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96 | HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. | Baseline, Week 48, Week 96 |
| Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96 | HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb) | Baseline, Week 48, Week 96 |
| Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96 | Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection | Week 48, Week 96 |
| Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96 | 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 | Week 48, Week 96 |
| Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96 | HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL | Week 48, Week 96 |
| San Francisco |
| California |
| 94118 |
| United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Local Institution | New York | New York | 10025 | United States |
| Local Institution | Brussels | 1200 | Belgium |
| Local Institution | Leuven | 3000 | Belgium |
| Local Institution | Berlin | 13353 | Germany |
| Local Institution | Bonn | 53105 | Germany |
| Local Institution | Düsseldorf | 40237 | Germany |
| Local Institution | Mainz | 55131 | Germany |
| Local Institution | Messina | 98124 | Italy |
| Local Institution | Modena | 41100 | Italy |
| Local Institution | Naples | 80135 | Italy |
| Local Institution | Padova | 35128 | Italy |
| Local Institution | San Giovanni Rotondo | 71013 | Italy |
| Local Institution | Chorzów | 41-500 | Poland |
| Local Institution | Krakow | 31-531 | Poland |
| Local Institution | Lublin | 20-089 | Poland |
| Local Institution | Ankara | 06010 | Turkey (Türkiye) |
| Local Institution | Ankara | 06620 | Turkey (Türkiye) |
| Local Institution | Istanbul | 34093 | Turkey (Türkiye) |
| Local Institution | Istanbul | 34098 | Turkey (Türkiye) |
| Local Institution | Istanbul | 34360 | Turkey (Türkiye) |
| Local Institution | Istanbul | 34460 | Turkey (Türkiye) |
| Local Institution | Istanbul | 34722 | Turkey (Türkiye) |
| Local Institution | Izmir | 35100 | Turkey (Türkiye) |
| Local Institution | Kocaeli | 41380 | Turkey (Türkiye) |
| Local Institution | Sihhiye Ankara | 06100 | Turkey (Türkiye) |
| Local Institution | Trabzon | 61080 | Turkey (Türkiye) |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Entecavir + Tenofovir | Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks |
| BG001 | Adefovir + Continuing Lamivudine | Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | participants |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48 | 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 | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | Participants | Week 48 |
|
| ||||||||||||||||||||
| Secondary | Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96 | by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA < 50 IU/mL = approximately 300 copies/mL. | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Week 96 |
|
| ||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities | 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. | All treated participants. Timeframe for Outcome Measure revised due to study termination. (Study Completion Date=February 2009). | Posted | Number | participants | Day 1 through end of treatment (Week 100 +/- 5 days) |
|
| ||||||||||||||||||||
| Secondary | Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96 | by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL) | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Week 48, Week 96 |
|
| ||||||||||||||||||||
| Secondary | HBV DNA Values at Weeks 48 and 96 | Number of Participants with HBV DNA \ | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Weeks 48, Week 96 |
|
| ||||||||||||||||||||
| Secondary | Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96 | by PCR, using the Roche COBAS®TaqMan - HPS assay | Due to early study termination, none of the efficacy endpoints was analyzed. | Posted | Mean | Standard Deviation | log10 | Week 48, Week 96 |
|
| |||||||||||||||||||
| Secondary | 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 | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | Participants | Week 48, Week 96 |
|
| |||||||||||||||||||||
| Secondary | Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96 | HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. | Due to early study termination, none of the efficacy endpoints was analyzed. | Posted | Number | Participants | Baseline, Week 48, Week 96 |
|
| ||||||||||||||||||||
| Secondary | Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96 | HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb) | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Baseline, Week 48, Week 96 |
|
| ||||||||||||||||||||
| Secondary | Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96 | Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Week 48, Week 96 |
|
| ||||||||||||||||||||
| Secondary | Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96 | 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 | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Week 48, Week 96 |
|
| ||||||||||||||||||||
| Secondary | Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96 | HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL | Due to early study termination, none of the efficacy endpoints were analyzed. | Posted | Number | participants | Week 48, Week 96 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Entecavir + Tenofovir | Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks | 0 | 1 | 1 | 1 | ||
| EG001 | Adefovir + Continuing Lamivudine | Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks | 0 | 1 | 1 | 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperchlorhydria | Gastrointestinal disorders |
| |||
| Hepatitis | Hepatobiliary disorders |
| |||
| Fatigue | General disorders |
|
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.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| BMS Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C413685 | entecavir |
| D000068698 | Tenofovir |
| C053001 | adefovir |
| ID | Term |
|---|---|
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Title | Measurements |
|---|---|
|
| Male |
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| Participants |
|
|