Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B
This study has been completed.
Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00410072
First received: December 11, 2006
Last updated: March 13, 2013
Last verified: March 2013
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Hepatitis B, Chronic |
Drug: Entecavir Drug: Entecavir + Tenofovir |
Phase 3 |
| 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:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]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:
- 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 ] [ Designated as safety issue: No ]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.
- Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]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.
- Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]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.
- 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.
- Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]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.
- Percentage 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 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.
- Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96 [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]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.
- Percentage 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. 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.
- Percentage 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.
- 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 ] [ 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.
- Number of Participants With HBV Resistance Through Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]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.
- Number of Participants With HBV Resistance at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]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.
- Number of Participants With Virologic Breakthrough at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed >= 1 log10 increase in HBV DNA from the on-treatment nadir
- Number of Participants With Virologic Breakthrough at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed >=1 log10 increase in HBV DNA from moving nadir
| 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: TDF 0.5 mg
TDF=tenofovir
|
Drug: Entecavir
Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks
Other Names:
|
|
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:
|
Eligibility| Ages Eligible for Study: | 16 Years and older |
| Genders Eligible for Study: | Both |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00410072
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| United States, California | |
| Sergio E. Rojter | |
| Los Angeles, California, United States, 90017 | |
| Tuan Nguyen, Md | |
| San Diego, California, United States, 92105 | |
| San Jose Gastroenterology | |
| San Jose, California, United States, 95128 | |
| United States, Connecticut | |
| Yale University School Of Medicine | |
| New Haven, Connecticut, United States, 06510 | |
| United States, Florida | |
| University Of Miami | |
| Miami, Florida, United States, 33136 | |
| United States, Georgia | |
| Atlanta Gastroenterology Associates | |
| Atlanta, Georgia, United States, 30308 | |
| Digestive Healthcare Of Georgia | |
| Atlanta, Georgia, United States, 30309 | |
| United States, Maryland | |
| Digestive Disease Associates, P.A. | |
| Baltimore, Maryland, United States, 21229 | |
| Maryland Digestive Disease Research, Llc | |
| Laurel, Maryland, United States, 20707 | |
| United States, Massachusetts | |
| Beth Israel Deaconess Medical Center | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Michigan | |
| University Of Michigan Health System | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, New York | |
| Sing Chan, Md | |
| Flushing, New York, United States, 11355 | |
| North Shore University | |
| Manhasset, New York, United States, 11030 | |
| Mount Sinai School Of Medicine | |
| New York, New York, United States, 10029 | |
| Beth Israel Medical Center | |
| New York, New York, United States, 10003 | |
| Concorde Medical Group | |
| New York, New York, United States, 10016 | |
| Argentina | |
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| Ciudad De Buenos Aires, Buenos Aires, Argentina, C1181ACH | |
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| Ciudad De Buenos Aires, Buenos Aires, Argentina, C1121ABE | |
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| Ciudad De Buenos Aires, Buenos Aires, Argentina, C1282AEN | |
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| Rosario, Prov De Santa, Argentina, S2000PBJ | |
| Australia, New South Wales | |
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| Westmead Nsw, New South Wales, Australia, 2145 | |
| Australia, Victoria | |
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| Clayton Vic, Victoria, Australia, 3168 | |
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| Fitzroy, Victoria, Australia, 3065 | |
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| Heidelberg, Victoria, Australia, 3084 | |
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| Prahan, Victoria, Australia, 3004 | |
| Brazil | |
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| Belo Horizonte, Minas Gerais, Brazil, 30150 | |
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| Porto Alegre Rs, Rio Grande Do Sul, Brazil, 90035 | |
| Canada, Alberta | |
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| Calgary, Alberta, Canada, T2N 4Z6 | |
| Canada, British Columbia | |
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| Vancouver, British Columbia, Canada, V5Z 1H2 | |
| Canada, Manitoba | |
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| Winnipeg, Manitoba, Canada, R3E 3P4 | |
| Canada, Ontario | |
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| Toronto, Ontario, Canada, M3N 2V7 | |
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| Toronto, Ontario, Canada, M5T 2S8 | |
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| Toronto, Ontario, Canada, M5G 2N2 | |
| France | |
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| Grenoble Cedex 09, France, 38043 | |
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| Marseille Cedex 08, France, 13285 | |
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| Paris, France, 75014 | |
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| Paris Cedex 12, France, 75571 | |
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| Paris Cedex 13, France, 75013 | |
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| Strasbourg, France, 67090 | |
| India | |
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| Hyderabad, Andhra Pradesh, India, 500082 | |
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| Lucknow, India, 226014 | |
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| Ludhiana, India, 141001 | |
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| Vellore, India, 632004 | |
| Italy | |
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| Antella Firenze, Italy, 50012 | |
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| Brescia, Italy, 25123 | |
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| Pisa, Italy, 56124 | |
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| Roma, Italy, 00149 | |
| Mexico | |
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| Durango, Mexico, 34229 | |
| Poland | |
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| Bialystok, Poland, 15-540 | |
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| Chorzow, Poland, 41-500 | |
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| Krakow, Poland, 31-531 | |
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| Lublin, Poland, 20-081 | |
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| Warszawa, Poland, 01-201 | |
| Russian Federation | |
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| Moscow, Russian Federation, 105275 | |
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| Moscow, Russian Federation, 115446 | |
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| Moscow, Russian Federation, 117593 | |
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| Smolensk, Russian Federation, 214018 | |
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| St. Petersburg, Russian Federation, 194044 | |
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| St. Petersburg, Russian Federation, 190103 | |
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| St. Petersburg, Russian Federation, 191167 | |
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| St. Petersburg, Russian Federation, 191163 | |
| South Africa | |
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| Pretoria, Gauteng, South Africa, 0001 | |
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| Bellville, Western Cape, South Africa, 7530 | |
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| N1 City Goodwood, Western Cape, South Africa, 7463 | |
| Turkey | |
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| Bornova Izmir, Turkey, 35100 | |
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| Cebeci Ankara, Turkey, 06620 | |
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| Sihhiye Ankara, Turkey, 06100 | |
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| Trabzon, Turkey, 61080 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided by Bristol-Myers Squibb
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | March 13, 2013 |
| 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 May 16, 2013