Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00410072
Recruitment Status : Completed
First Posted : December 12, 2006
Results First Posted : February 3, 2012
Last Update Posted : March 15, 2013
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this study is to compare the effectiveness of entecavir plus tenofovir combination therapy with that of entecavir monotherapy. Safety will also be studied.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Entecavir Drug: Entecavir + Tenofovir Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 669 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : April 2007
Actual Primary Completion Date : October 2010
Actual Study Completion Date : October 2010

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: TDF 0.5 mg
TDF=tenofovir
 Drug: Entecavir
Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks
Other Names:
  • Baraclude
  • BMS-200475
Experimental: ETV 0.5 mg +TDF 300 mg
ETV=entecavir; TDF=tenofovir
 Drug: Entecavir + Tenofovir
Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks
Other Names:
  • Baraclude
  • BMS-200475


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96 [ Time Frame: At Week 96 ]
    HBV DNA levels <50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.


Secondary Outcome Measures :
  1. Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status [ Time Frame: At Weeks 48 and 96 ]
    HBV DNA levels <50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  2. Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    LOQ=lower limit of quantitation. LOQ=29 IU/mL, or approximately 169 copies/mL. 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.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  3. Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    LOD=Lower limit of detection. LOD) LOD=10 IU/mL, or approximately 58 copies/mL. 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.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  4. Mean Log 10 HBV DNA at Weeks 48 and 96 [ Time Frame: Baseline, Weeks 48 and 96 ]
    HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan - HPS assay. Reduction in Log 10 HBV count=reduced viral load.

  5. Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    ALT normalization= ≤1*upper limit of normal (ULN). Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  6. Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    HBeAg is a hepatitis B viral protein and is an indicator of active viral replication. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  7. Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    HBeAg seroconversion=HBeAg loss and presence of hepatitis B e antibody (HBeAb). HBeAg is a hepatitis B viral protein and is an indicator of active viral replication.

  8. Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    HBsAg = A part of the hepatitis B virus. When found in the blood, HBsAg is an early marker of infection. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  9. Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.

  10. Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ]
    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.

  11. Number of 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 ]
    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.

  12. Number of Participants With HBV Resistance Through Week 48 [ Time Frame: Week 48 ]
    ETVr=entecavir resistance; TDFr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.

  13. Number of Participants With HBV Resistance at Week 96 [ Time Frame: Week 96 ]
    ETVr=entecavir resistance; TFDr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.

  14. Number of Participants With Virologic Breakthrough at Week 48 [ Time Frame: Week 48 ]
    ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed >= 1 log10 increase in HBV DNA from the on-treatment nadir

  15. Number of Participants With Virologic Breakthrough at Week 96 [ Time Frame: Week 96 ]
    ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed >=1 log10 increase in HBV DNA from moving nadir


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic hepatitis B virus (HBV) infection (hepatitis B e antigen [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*10*5*IU/mL (approximately 10*6*copies/mL) for HbeAg-positive participants
  • HBV DNA >1.72*10*4*IU/mL (approximately 10*5*copies/mL) for Hbe-Ag-negative participants
  • Alanine aminotransferase level ≥*upper limit of normal (ULN) and ≤10*ULN

Exclusion Criteria:

  • Evidence of decompensated cirrhosis
  • Coinfection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
  • Laboratory values out of protocol-specified range
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00410072


Locations
Show Show 68 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00410072    
Other Study ID Numbers: AI463-110
First Posted: December 12, 2006    Key Record Dates
Results First Posted: February 3, 2012
Last Update Posted: March 15, 2013
Last Verified: March 2013
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
 Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents