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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00410072
Registration number
NCT00410072
Ethics application status
Date submitted
11/12/2006
Date registered
12/12/2006
Date last updated
15/03/2013
Titles & IDs
Public title
Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B
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Scientific 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
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Secondary ID [1]
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AI463-110
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic
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Condition category
Condition code
Infection
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Other infectious diseases
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Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Entecavir
Treatment: Drugs - Entecavir + Tenofovir
Experimental: TDF 0.5 mg - TDF=tenofovir
Experimental: ETV 0.5 mg +TDF 300 mg - ETV=entecavir; TDF=tenofovir
Treatment: Drugs: Entecavir
Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks
Treatment: Drugs: Entecavir + Tenofovir
Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96
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Assessment method [1]
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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.
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Timepoint [1]
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At Week 96
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Secondary outcome [1]
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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
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Assessment method [1]
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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.
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Timepoint [1]
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At Weeks 48 and 96
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Secondary outcome [2]
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Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96
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Assessment method [2]
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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.
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Timepoint [2]
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At Weeks 48 and 96
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Secondary outcome [3]
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Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96
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Assessment method [3]
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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.
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Timepoint [3]
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At Weeks 48 and 96
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Secondary outcome [4]
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Mean Log 10 HBV DNA at Weeks 48 and 96
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Assessment method [4]
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HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan - HPS assay. Reduction in Log 10 HBV count=reduced viral load.
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Timepoint [4]
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Baseline, Weeks 48 and 96
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Secondary outcome [5]
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Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96
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Assessment method [5]
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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.
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Timepoint [5]
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At Weeks 48 and 96
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Secondary outcome [6]
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Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96
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Assessment method [6]
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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.
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Timepoint [6]
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At Weeks 48 and 96
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Secondary outcome [7]
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Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96
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Assessment method [7]
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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.
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Timepoint [7]
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At Weeks 48 and 96
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Secondary outcome [8]
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96
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Assessment method [8]
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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.
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Timepoint [8]
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At Weeks 48 and 96
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Secondary outcome [9]
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Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96
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Assessment method [9]
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HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.
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Timepoint [9]
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At Weeks 48 and 96
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Secondary outcome [10]
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Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96
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Assessment method [10]
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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.
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Timepoint [10]
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At Weeks 48 and 96
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Secondary outcome [11]
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Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities
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Assessment method [11]
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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.
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Timepoint [11]
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From enrollment through Week 100 + 24-week follow-up
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Secondary outcome [12]
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Number of Participants With HBV Resistance Through Week 48
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Assessment method [12]
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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.
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Timepoint [12]
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Week 48
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Secondary outcome [13]
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Number of Participants With HBV Resistance at Week 96
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Assessment method [13]
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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.
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Timepoint [13]
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Week 96
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Secondary outcome [14]
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Number of Participants With Virologic Breakthrough at Week 48
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Assessment method [14]
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ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed >= 1 log10 increase in HBV DNA from the on-treatment nadir
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Timepoint [14]
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Week 48
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Secondary outcome [15]
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Number of Participants With Virologic Breakthrough at Week 96
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Assessment method [15]
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ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed >=1 log10 increase in HBV DNA from moving nadir
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Timepoint [15]
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Week 96
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Eligibility
Key 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
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Minimum age
16
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/04/2007
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/10/2010
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Sample size
Target
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Accrual to date
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Final
669
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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Local Institution - Westmead Nsw
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Recruitment hospital [2]
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Local Institution - Clayton Vic
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Recruitment hospital [3]
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Local Institution - Fitzroy
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Recruitment hospital [4]
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Local Institution - Heidelberg
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Recruitment hospital [5]
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Local Institution - Prahan
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Recruitment postcode(s) [1]
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2145 - Westmead Nsw
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Recruitment postcode(s) [2]
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3168 - Clayton Vic
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Recruitment postcode(s) [3]
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3065 - Fitzroy
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Recruitment postcode(s) [4]
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3084 - Heidelberg
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Recruitment postcode(s) [5]
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3004 - Prahan
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Connecticut
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United States of America
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State/province [3]
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Florida
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Country [4]
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United States of America
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Georgia
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Country [5]
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United States of America
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State/province [5]
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Maryland
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Country [6]
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United States of America
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State/province [6]
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Massachusetts
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Country [7]
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United States of America
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State/province [7]
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Michigan
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Country [8]
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United States of America
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State/province [8]
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New York
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Country [9]
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Argentina
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State/province [9]
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Buenos Aires
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Country [10]
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Argentina
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State/province [10]
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Prov De Santa
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Country [11]
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Brazil
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State/province [11]
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Minas Gerais
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Country [12]
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Brazil
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State/province [12]
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Rio Grande Do Sul
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Country [13]
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Canada
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State/province [13]
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Alberta
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Country [14]
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Canada
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State/province [14]
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British Columbia
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Country [15]
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Canada
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State/province [15]
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Manitoba
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Country [16]
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Canada
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State/province [16]
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Ontario
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Country [17]
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France
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Grenoble Cedex 09
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Country [18]
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France
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State/province [18]
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Marseille Cedex 08
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Country [19]
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France
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State/province [19]
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Paris Cedex 12
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Country [20]
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France
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Paris Cedex 13
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Country [21]
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France
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Paris
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France
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State/province [22]
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Strasbourg
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Country [23]
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India
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State/province [23]
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Andhra Pradesh
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India
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Lucknow
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India
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Ludhiana
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India
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Vellore
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Italy
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State/province [27]
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Antella Firenze
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Italy
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Brescia
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Italy
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Pisa
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Italy
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State/province [30]
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Roma
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Country [31]
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Mexico
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State/province [31]
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Durango
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Poland
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State/province [32]
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Bialystok
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Poland
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State/province [33]
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Chorzow
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Poland
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State/province [34]
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Krakow
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Poland
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State/province [35]
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Lublin
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Poland
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State/province [36]
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Warszawa
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Country [37]
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Russian Federation
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State/province [37]
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Moscow
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Country [38]
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Russian Federation
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State/province [38]
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Smolensk
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Country [39]
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Russian Federation
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State/province [39]
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St. Petersburg
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Country [40]
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South Africa
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State/province [40]
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Gauteng
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Country [41]
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South Africa
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State/province [41]
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Western Cape
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Country [42]
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Turkey
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State/province [42]
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Bornova Izmir
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Country [43]
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Turkey
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State/province [43]
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Cebeci Ankara
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Country [44]
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Turkey
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State/province [44]
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Sihhiye Ankara
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Country [45]
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Turkey
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State/province [45]
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Trabzon
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Bristol-Myers Squibb
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00410072
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Bristol-Myers Squibb
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Address
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Bristol-Myers Squibb
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00410072
Download to PDF