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 - Full Text View

Sponsor:	Bristol-Myers Squibb
Information provided by:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00605384

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 III

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:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Adefovir Lamivudine Entecavir Adefovir dipivoxil Tenofovir Tenofovir disoproxil 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

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

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 February 09, 2012