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
This study has been terminated.
(Business Objectives Have Changed)
Sponsor:
Bristol-Myers Squibb
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00605384
First received: January 18, 2008
Last updated: November 15, 2010
Last verified: November 2010
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Hepatitis B |
Drug: Entecavir + Tenofovir Drug: Adefovir + continuing Lamivudine |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Comparative Study of the Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Versus Adefovir Added to Continuing Lamivudine in Adults With Lamivudine- Resistant Chronic Hepatitis B Virus Infection |
Resource links provided by NLM:
Drug Information available for:
Lamivudine
Entecavir
Adefovir dipivoxil
Tenofovir
Tenofovir Disoproxil Fumarate
U.S. FDA Resources
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]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
Secondary Outcome Measures:
- Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA < 50 IU/mL = approximately 300 copies/mL.
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities [ Time Frame: Day 1 through end of treatment (Week 100 +/- 5 days) ] [ Designated as safety issue: Yes ]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.
- Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)
- HBV DNA Values at Weeks 48 and 96 [ Time Frame: Weeks 48, Week 96 ] [ Designated as safety issue: No ]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
- Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]by PCR, using the Roche COBAS®TaqMan - HPS assay
- 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 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
- Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
- Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb)
- Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection
- Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]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
- Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL
| Enrollment: | 4 |
| Study Start Date: | August 2008 |
| Study Completion Date: | February 2009 |
| Primary Completion Date: | February 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Drug: Entecavir + Tenofovir
Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Other Name: Baraclude
|
| Experimental: 2 |
Drug: Adefovir + continuing Lamivudine
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Chronic HBV infection
- History of lamivudine (LVD) treatment, and lamivudine resistance (LVDr), receiving LVD at screening visit
- Compensated liver function
- HBV DNA ≥ 172,000 IU/mL
- Hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative
Exclusion Criteria:
- Evidence of decompensated cirrhosis
- Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
- Recent history of pancreatitis
- Serum alpha fetoprotein > 100 ng/mL
- Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00605384
Locations
| United States, California | |
| Cedars Sinai Medical Center | |
| Los Angeles, California, United States, 90048 | |
| Kaiser Permanente Medical Center | |
| San Francisco, California, United States, 94118 | |
| United States, Illinois | |
| Rush University Medical Center | |
| Chicago, Illinois, United States, 60612 | |
| United States, New York | |
| Local Institution | |
| New York, New York, United States, 10025 | |
| Belgium | |
| Local Institution | |
| Bruxelles, Belgium, 1200 | |
| Local Institution | |
| Leuven, Belgium, 3000 | |
| Germany | |
| Local Institution | |
| Berlin, Germany, 13353 | |
| Local Institution | |
| Bonn, Germany, 53105 | |
| Local Institution | |
| Duesseldorf, Germany, 40237 | |
| Local Institution | |
| Mainz, Germany, 55131 | |
| Italy | |
| Local Institution | |
| Messina, Italy, 98124 | |
| Local Institution | |
| Modena, Italy, 41100 | |
| Local Institution | |
| Naples, Italy, 80135 | |
| Local Institution | |
| Padova, Italy, 35128 | |
| Local Institution | |
| San Giovanni Rotondo, Italy, 71013 | |
| Poland | |
| Local Institution | |
| Chorzow, Poland, 41-500 | |
| Local Institution | |
| Krakow, Poland, 31-531 | |
| Local Institution | |
| Lublin, Poland, 20-089 | |
| Turkey | |
| Local Institution | |
| Ankara, Turkey, 06010 | |
| Local Institution | |
| Ankara, Turkey, 06620 | |
| Local Institution | |
| Istanbul, Turkey, 34460 | |
| Local Institution | |
| Istanbul, Turkey, 34360 | |
| Local Institution | |
| Istanbul, Turkey, 34722 | |
| Local Institution | |
| Istanbul, Turkey, 34093 | |
| Local Institution | |
| Istanbul, Turkey, 34098 | |
| Local Institution | |
| Izmir, Turkey, 35100 | |
| Local Institution | |
| Kocaeli, Turkey, 41380 | |
| Local Institution | |
| Sihhiye Ankara, Turkey, 06100 | |
| Local Institution | |
| Trabzon, Turkey, 61080 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Study Director, Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00605384 History of Changes |
| Other Study ID Numbers: | AI463-137 |
| Study First Received: | January 18, 2008 |
| Results First Received: | July 13, 2010 |
| Last Updated: | November 15, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis B Hepatitis, Chronic Hepatitis B, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections Adefovir |
Adefovir dipivoxil Lamivudine Tenofovir Tenofovir disoproxil Entecavir Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |
ClinicalTrials.gov processed this record on May 23, 2013