Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-Resistant Virus - Full Text View

Sponsored by:	Bristol-Myers Squibb
Information provided by:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00410202

Purpose

The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine

Condition	Intervention	Phase
Hepatitis B, Chronic	Drug: Entecavir Drug: Adefovir + Lamivudine Drug: Entecavir + Adefovir	Phase III

MedlinePlus related topics: Hepatitis Hepatitis B

Drug Information available for: Lamivudine Hepatitis B Vaccines Adefovir dipivoxil Adefovir Entecavir

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Comparative Study of Entecavir vs. Adefovir Plus Lamivudine vs Combination Entecavir Plus Adefovir in Lamivudine-Resistant Chronic Hepatitis B Subjects: The DEFINE Study

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

To compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the monotherapy groups who achieve HBV DNA <50 IU/mL (approximately 300 copies/mL) [ Time Frame: at Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the monotherapy groups who achieve HBV DNA <50 IU/mL (approximately 300 copies/mL) [ Time Frame: at Week 96 ] [ Designated as safety issue: No ]
Mean Log10 reduction from baseline in HBV DNA [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
ALT normalization (≤ 1 x upper limit of normal) [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBeAg loss [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBe seroconversion [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBs seroconversion [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
Virologic rebound due to genotypic resistance [ Time Frame: upon occurrence ] [ Designated as safety issue: No ]
Frequency of adverse events, serious adverse events, and discontinuations from study drug due to adverse events or laboratory abnormalities [ Time Frame: upon occurrence ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	420
Study Start Date:	March 2008
Estimated Study Completion Date:	February 2012
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A1: Experimental	Drug: Entecavir Tablets, Oral, ETV = 1mg, once daily, 100 weeks
B1: Experimental	Drug: Adefovir + Lamivudine Tablets, Oral, Adefovir 10 mg + Lamivudine 100 mg, once daily, 100 weeks
C1: Experimental	Drug: Entecavir + Adefovir Tablets, Oral, ETV = 1 mg + Adefovir 10 mg once daily, 100 weeks

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Evidence of lamivudine resistance
Chronic HBV infection with HbeAg-positive disease
Nucleoside- and nucleotide-naive, except for lamivudine
Males or females ≥16 years of age (or minimum age of consent in a given country)
Compensated liver function
HBV DNA > 1.72 x 10*4* (approximately 10*5* copies/mL)
ALT ≤10 x upper limit of normal

Exclusion Criteria:

Evidence of decompensated cirrhosis
Coinfection with HIV, HCV, or HDV
Laboratory values out of protocol-specified range

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410202

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Show 74 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More 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

Responsible Party:	Bristol-Myers Squibb ( Study Director )
Study ID Numbers:	AI463-111
Study First Received:	December 11, 2006
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00410202
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Liver Diseases
Hepatitis, Chronic
Hepatitis, Viral, Human
Lamivudine
Hepatitis
Virus Diseases
Digestive System Diseases

Entecavir
Hepatitis B, Chronic
Hepatitis B
DNA Virus Infections
Adefovir dipivoxil
Adefovir

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Enzyme Inhibitors

Antiviral Agents
Hepadnaviridae Infections
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009