Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B - Full Text View

Sponsor:	Bristol-Myers Squibb
Information provided by (Responsible Party):	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00410072

Purpose

The purpose of this study is to evaluate the effectiveness of entecavir plus tenofovir combination therapy compared with entecavir monotherapy. Safety will also be studied

Condition	Intervention	Phase
Hepatitis B, Chronic	Drug: Entecavir Drug: Entecavir + Tenofovir	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 Chronic Hepatitis B Subjects Treated With Entecavir Plus Tenofovir Combination Therapy vs. Entecavir Monotherapy in Adults Who Are Treatment-Naive to Nucleosides and Nucleotides: The BE-LOW Study

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Entecavir 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 in Each Treatment Group Who Achieve Hepatitis B Virus DNA (HBV DNA) <50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 96 [ Time Frame: at Week 96 ] [ Designated as safety issue: No ]
using the Roche COBAS® TaqMan HBV Test for use with the High Pure System (HPS) assay, by PCR; HBV DNA < 50 IU/mL = approximately 300 copies/mL

Secondary Outcome Measures:

Number of Participants in Each Treatment Group Who Achieve: HBV DNA <50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 48 and Week 96 [ Time Frame: at Week 48, 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 Who Achieve HBV DNA < LOQ (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) by PCR at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
Lower limit of quantitation (LOQ) is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.
Number of Participants Who Achieve HBV DNA < LOD (LOD = 10 IU/mL [Approximately 58 Copies/mL]) by PCR at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
Lower limit of detection (LOD) is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.
Mean Log 10 HBV DNA at Weeks 48 and 96 [ Time Frame: Baseline, Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan - HPS assay. Reduction in Log 10 HBV count=reduced viral load.
Number of Participants With Alanine Aminotransferase (ALT) Normalization [(≤ 1 x Upper Limit of Normal (ULN)] at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
The ULN is 37 U/L.
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
Number of Participants With HBeAg Seroconversion [(HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb)] at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.
Number of Participants With HBsAg Seroconversion at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
using the Roche COBAS TaqMan - HPS assay. Lower limit of Quantitation (LOQ) is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.
Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities [ Time Frame: From enrollment through Week 100 + 24-week follow-up ] [ Designated as safety issue: Yes ]
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
HBV Resistance Through Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples from subjects at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used. Genotypic HBV resistance testing will be performed on specimens with HBV DNA > 50 IU/mL at Weeks 48 and 96, and at any time point at which virologic breakthrough occurs.

Enrollment:	669
Study Start Date:	April 2007
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A1	Drug: Entecavir Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks Other Names: Baraclude BMS-200475
Experimental: B2	Drug: Entecavir + Tenofovir Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks Other Names: Baraclude BMS-200475

Eligibility

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

Criteria

Inclusion Criteria:

Chronic HBV infection (HbeAg-positive or negative) disease
Nucleoside- and nucleotide-naive
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*5* IU/mL (approximately 10*6* copies/mL) for HbeAg-positive subjects
HBV DNA >1.72 x 10*4* IU/mL (approximately 10*5* copies/mL) for Hbe-Ag-negative subjects
ALT ≥ x upper limit of normal and ≤ 10 x upper limit of normal

Exclusion Criteria:

Evidence of decompensated cirrhosis
Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
Laboratory values out of protocol-specified range

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410072

Show 68 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:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00410072 History of Changes
Other Study ID Numbers:	AI463-110
Study First Received:	December 11, 2006
Results First Received:	November 4, 2011
Last Updated:	January 3, 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

Tenofovir
Tenofovir disoproxil
Entecavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 12, 2012