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

Sponsor:	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: Tenofovir Drug: Adefovir Drug: 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 Entecavir vs. Adefovir Plus Lamivudine vs Combination Entecavir Plus Adefovir in Lamivudine-resistant Chronic Hepatitis B Subjects: The DEFINE Study

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:

Compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the comparator therapy 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:

Proportion of subjects who achieve HBV DNA < the lower limit of quantitation (LLD LOQ) for the Roche COBAS® TaqMan -(LOQ = 29 IU/mL [approximately 169 copies/mL] [ Time Frame: HPS assay at Weeks 48 and 96 ] [ Designated as safety issue: No ]
Proportion of subjects who achieve HBV DNA < the lower limit of detection (LOD) for the Roche COBAS® Taqman - (LOD = 10 IU/mL [approximately 58 copies/mL]) [ Time Frame: HPS assay at Weeks 48 and 96 ] [ Designated as safety issue: No ]
Proportions of subjects with HBV DNA in clinically relevant categories (eg HBV DNA values categorized in ranges that differ by 10 log increments) [ Time Frame: at 48 weeks ] [ Designated as safety issue: No ]
Proportion of subjects with ALT > 1 x upper limit of normal (ULN) at baseline who achieve ALT normalization (<= 1 x ULN) [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
Descriptive rates of resistance in each treatment arm [ Time Frame: through Weeks 48 and 96 ] [ Designated as safety issue: No ]

Estimated Enrollment:	420
Study Start Date:	March 2008
Estimated Study Completion Date:	July 2012
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Entecavir With the option of adding Tenofovir at week 48. (This does not apply to Korea)	Drug: Entecavir Tablets, Oral, 1mg, once daily, 100 weeks Other Names: Baraclude BMS-200475 Drug: Tenofovir Tablets, Oral, 300 mg, once daily Other Name: Viread
Active Comparator: Adefovir + Lamivudine	Drug: Adefovir Tablets, Oral, 10mg, once daily, 100 weeks Other Name: Hepsera Drug: Lamivudine Tablets, Oral, 100mg, once daily, 100 weeks Other Name: Epivir
Active Comparator: Entecavir + Adefovir	Drug: Entecavir Tablets, Oral, 1mg, once daily, 100 weeks Other Names: Baraclude BMS-200475 Drug: Adefovir Tablets, Oral, 10mg, once daily, 100 weeks Other Name: Hepsera

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
Subjects must have a history of previous lamivudine treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S)
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)
Documentation of HBeAg-positive and HBeAb-negative status at screening
Males and females >=16 years of age (or minimum age of consent in a given country)
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized
WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post menopausal is defined as:
Amenorrhea >= 12 consecutive months without another cause
For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product

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

Show 67 Study Locations

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

Investigator Inquiry form 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:	NCT00410202 History of Changes
Other Study ID Numbers:	AI463-111
Study First Received:	December 11, 2006
Last Updated:	January 13, 2012
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 12, 2012