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Comparison of Entecavir to Adefovir in Chronic Hepatitis B Virus (HBV) Patients With Hepatic Decompensation

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00065507
Collaborator
(none)
195
Enrollment
61
Locations
2
Arms
117
Duration (Months)
3.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase IIIb comparative study of entecavir 1.0 mg once daily (QD) vs. adefovir 10 mg QD in patients who have chronic hepatitis B infection and hepatic decompensation. The patients are treated for 96 weeks after the last subject is randomized.

Condition or Disease Intervention/Treatment Phase
  • Drug: Entecavir (ETV)
  • Drug: Adefovir (ADV)
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
195 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Comparison of the Efficacy and Safety of Entecavir Versus Adefovir in Subjects Chronically Infected With Hepatitis B Virus and Evidence of Hepatic Decompensation
Study Start Date :
Aug 1, 2003
Actual Primary Completion Date :
Oct 1, 2008
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: A1

Drug: Entecavir (ETV)
Tablets, Oral, 1 mg once daily, 96 weeks from the time the last patient is randomized
Other Names:
  • Baraclude
  • BMS-200475

    		•
    Active Comparator: A2

    Drug: Adefovir (ADV)
    Tablets, Oral, 10 mg, once daily, 96 weeks from the time the last patient is randomized

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24 [Baseline, Week 24]

      Mean reduction in serum HBV DNA determined by PCR assay (log10 copies/mL) at Week 24 adjusted for baseline HBV DNA and lamivudine resistance (LVDr) status, based on linear regression analysis.

    Secondary Outcome Measures

    1. Change From Baseline in HBV DNA by PCR at Week 48 [Baseline, Week 48]

      Mean change from baseline in HBV DNA by PCR at Week 48, adjusted for baseline HBV DNA and LVDr Status.

    2. Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24 [Week 24]

    3. Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48 [Week 48]

    4. Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48 [Week 24, Week 48]

      Number of participants in each group who achieved ALT normalization (≤1.0 x upper limit of normal [ULN]) among those with baseline ALT >1.0 x ULN at Weeks 24 and 48

    5. Number of Subjects Achieving Composite Endpoint (HBV DNA < 10*4 Copies/mL by PCR Assay and Normal ALT [≤ 1.0 x ULN]) Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 48]

    6. >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis).

    7. Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 48]

      Number of participants in each group with improvement or no worsening in Child-Pugh score from baseline to Week 48 as measured by improvement or no worsening in Child-Pugh score. Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis).

    8. Change From Baseline in Child-Pugh Score Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Mean change from baseline in Child-Pugh score through week 48. Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis).

    9. Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48 [Week 24, Week 48]

      Number of Participants in each group with improvement in Child-Pugh score from baseline to Week 48 as measured by improvement in Child-Pugh class. Improvement in Child-Pugh Class is defined as change from B to A or C to A. Evaluable subjects are subjects with Child-Pugh Class B or C at Baseline. Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis). Child-Pugh class A to C employs the added score from above: 5-6=Class A; 7-9=Class B; 10-15=Class C.

    10. Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Adjusted mean change from baseline in MELD score through Week 48 (adjusted for baseline value). The Model for End-Stage Liver Disease (MELD), is a scoring system for assessing the severity of chronic liver disease. MELD uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. In interpreting the MELD Score in hospitalized patients, the 3 month mortality is: 40 or more=100% mortality; 30-39=83% mortality; 20-29=76% mortality; 10-19=27% mortality; <10=4% mortality.

    11. Improvement or No Worsening in MELD Score Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 48]

      Participants with improvement or no worsening (any decrease or no change from baseline in score) in MELD score through Week 48. The Model for End-Stage Liver Disease (MELD), is a scoring system for assessing the severity of chronic liver disease. MELD uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. In interpreting the MELD Score in hospitalized patients, the 3 month mortality is: 40 or more=100% mortality; 30-39=83% mortality; 20-29=76% mortality; 10-19=27% mortality; <10=4% mortality.

    12. Mean Changes From Baseline in Quality of Life as Measured by the Short Form 36 (SF-36) [Baseline, Week 24, Week 48]

      Scoring for the SF-36 will be done using the algorithm developed by the Research ANd Development(RAND) Corporation (a scale of 0-100). Higher scores represent better quality of life. Coding for items with 2-category responses=0 and 100; 3-category=0/50/100; 5-category=0/25/50/75/100; 6-category=0/20/40/60/80/100. Scores of items in the same scale are combined to create the 8 scale scores (physical functioning, role-physical, bodily-pain, general health, vitality, social functioning, role-emotional, mental health). Physical and mental health composite scores will be computed for the group.

    13. Mean Changes From Baseline in Quality of Life, as Measured by EuroQol-5D (EQ-5D) at Weeks 24 and 48 [Baseline, Week 24, Week 48]

      The EQ-5D has 5 attributes (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression), each with 3 levels (no problem, some problems, and major problems). This algorithm gives valuation (weights) to each of the 15 responses on the form. Each valuation is a negative number, subtracted from the maximum score of 1 (perfect well being). The overall health index score ranges from 0 (dead) to 1 (perfect health) value scale, and the visual analog scale ranges from 0 to 100. Item weights will be obtained from the EuroQol group.

    14. Change From Baseline in Albumin Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Mean albumin levels, and mean change from baseline in albumin, a measure of synthetic liver function. Normal range for albumin = 3.5 - 5.3 g/dL.

    15. Mean Change From Baseline in Prothrombin Time Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Mean prothrombin time, and mean change from baseline in prothrombin time, a measure of synthetic liver function. Prothrombin time is the time it takes (in seconds) for a sample of blood to clot. Normal range for prothrombin time (PT) = 10-13 seconds.

    16. Mean Change From Baseline in Total Bilirubin Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Mean total bilirubin levels, and mean change from baseline in total bilirubin, a measure of liver secretory function.Normal range for total bilirubin = 0.2 - 1.2 mg/dL.

    17. Change From Baseline in Platelet Count Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Mean baseline platelet count and mean change from baseline in platelet count at specific timepoints. Platelets are the smallest particles found in the blood, which play a major role in forming blood clots. Normal range for platelets = 140 - 450 X 10*9 c/L.

    18. Participants Achieving Albumin Normalization Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Number of participants who achieved normalization of albumin (>= 1 x lower limit of normal [LLN]), a measure of liver function, at specific timepoints.

    19. Participants Achieving Prothrombin Time Normalization Through Week 48 [Baseline, Week4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Number of participants who achieved normalization of prothrombin time (<= 1 x ULN), a measure of liver function, at specific timepoints.

    20. Participants Achieving Total Bilirubin Normalization Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Number of participants who achieved normalization of total bilirubin (<= 1 x ULN), a measure of liver function, at specific timepoints.

    21. Participants Achieving Platelet Count Normalization Through Week 48 [Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48]

      Number of participants who achieved normalization of platelet count (>= 1 x lower limit of normal [LLN]), a measure of liver function, at specific timepoints.

    22. Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 [Week 48]

      HCC-free survival was analyzed using life tables. Measured values show the number of HCC events among treated participants at given time points.

    23. Cumulative Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, HCC, Discontinuations Due to AEs, and Confirmed Creatinine Increase >=0.5 mg/dL [on-treatment events obtained after the start of therapy and no more than 5 days after the last dose of study therapy.]

      AE=any new untoward medical occurrence/worsening of a pre-existing medical condition regardless of causal relationship. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires/prolongs inpatient hospitalization; results in persistent/significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. Confirmed increase in serum creatinine=values ≥0.5 mg/dL compared with baseline on 2 sequential measures.

    24. Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data [Week 48=all on-treatment laboratory measurements up to Week 48. Cumulative data = on-treatment laboratory measurements obtained after the start of therapy and no more than 5 days after the last dose of study therapy.]

      Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 48 data set was used to evaluate the Week-48 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death.

    25. Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment [On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date.]

      ALT flare=ALT > 2 x baseline and > 10 x upper limit of normal (ULN) by clinical laboratory evaluation. Table includes number of participants with selected clinical events and/or laboratory abnormalities during ALT flares. Selected clinical events during ALT flares=ascites, hepatic encephalopathy, jaundice, bacterial peritonitis. Selected Laboratory abnormalities during ALT flares=international normalized ratio > 1.5 or prothrombin time >= 1.2 x ULN and total bilirubin >2.5 mg/dL and > 1 mg/dL increase from baseline.

    26. Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period [On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.]

      Data includes type of malignant neoplasm.

    27. Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up [On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion

    • Child-Pugh (CP) score >= 7

    • Hepatitis B virus (HBV) viremia

    Exclusion

    • Alanine aminotransferase (ALT) > 15 x upper limit of normal (ULN)

    • Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)/hepatitis D virus (HDV) coinfection

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research And Education, Inc. San Diego California United States 92115
    2 California Pacific Medical Center San Francisco California United States 94115
    3 Yale University School Of Medicine New Haven Connecticut United States 06520
    4 University Of Miami School Of Medicine Miami Florida United States 33136
    5 Pediatric Gasteroenterology Atlanta Georgia United States 30342
    6 Hawaii Medical Center East Honolulu Hawaii United States 96817
    7 Indiana University Med Center Indianapolis Indiana United States 46202-5121
    8 The Cht Liver Research Center Louisville Kentucky United States 40292
    9 Johns Hopkins University Baltimore Maryland United States 21205
    10 Henry Ford Health System Irb Detroit Michigan United States 48202
    11 Mount Sinai Medical Center New York New York United States 10029
    12 Columbia Presbyterian Medical Center (Cpmc) New York New York United States 10032
    13 Integris Baptist Medical Center Oklahoma City Oklahoma United States 73112
    14 Baylor University Medical Center Dallas Texas United States 75246
    15 Ut Southwestern Medical Center Dallas Texas United States 75390-9151
    16 Mcguire Dvamc Richmond Virginia United States 23249
    17 Local Institution Porto Alegre - Rs Rio Grande Do Sul Brazil 90035-003
    18 Local Institution Sao Paulo - Sp Sao Paulo Brazil 05403-900
    19 Local institution Sao Paulo Brazil 01246-000
    20 Local Institution Sao Paulo Brazil 01246-903
    21 Local Institution Calgary Alberta Canada T2N 4N1
    22 Local Institution Vancouver British Columbia Canada V5Z 1H2
    23 Local Institution Clichy Cedex France 92118
    24 Local Institution Strasbourg France 67100
    25 Local institution Athens Greece 11522
    26 Local Institution Athens Greece 11527
    27 Local Institution Athens Greece 15127
    28 Local Instituition Thessaloniki Greece 54006
    29 Local Institution Thessaloniki Greece 570 10
    30 Local Institution Tai Po Hong Kong
    31 Local Institution Hyderabad Andhra Pradesh India 500082
    32 Local Institution Kolkata India 700020
    33 Local Institution Lucknow India 226014
    34 Local Institution New Delhi India 110002
    35 Local Institution Jakarta Indonesia 10430
    36 Local Institution Cebu Philippines 6000
    37 Local Institution Manila Philippines 1008
    38 Local Institution Bydgoszcz Poland 85-030
    39 Local Institution Chorzow Poland 41-500
    40 Local Institution Krakow Poland 31-202
    41 Local Institution Lodz Poland 91-347
    42 Local Institution Moscow Russian Federation 115446
    43 Local Institution Moscow Russian Federation 117333
    44 Local Institution Smolensk Russian Federation 214018
    45 Local Institution Singapore Singapore 119228
    46 Local Institution Singapore Singapore 169608
    47 Local Institution Singapore Singapore 308433
    48 Local Institution Singapore Singapore 529889
    49 Local Institution Observatory Western Cape South Africa 7925
    50 Local Institution Paarl Western Cape South Africa 7620
    51 Local Institution Changhua Taiwan 500
    52 Local Institution Taichung Taiwan 404
    53 Local Institution Taipei Taiwan 100
    54 Local Institution Taoyuan Taiwan 333
    55 Local Institution Tianan Taiwan 704
    56 Local Institution Bangkok Thailand 10400
    57 Local Institution Bangkok Thailand 10700
    58 Local Institution Hatyai Thailand 90110
    59 Local Institution Adana Turkey 01330
    60 Local Institution Izmir Turkey 35100
    61 Local Institution London Greater London United Kingdom NW3 2QG

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00065507
    Other Study ID Numbers:
    • AI463-048
    First Posted:
    Jul 29, 2003
    Last Update Posted:
    Jun 24, 2013
    Last Verified:
    Jun 1, 2013
    Keywords provided by Bristol-Myers Squibb
    hepatic decompensation
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis
    Entecavir
    Adefovir

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 431 participants were enrolled into the study. 236 were never randomized (213 no longer met study criteria; 6 withdrew consent; 3 died; 1 for administrative reasons by sponsor; 1 for adverse events; 1 lost to follow-up; 11 for other reasons).
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Period Title: Overall Study
    STARTED 100 91
    Treated (As-Randomized Population) 100 91
    Treated (As-Treated Population) 102 89
    Treated, Wk 48 (As-Treated Population) 102 89
    Treated, 24-Week Follow-Up Population 25 28
    COMPLETED 71 62
    NOT COMPLETED 29 29

    Baseline Characteristics

    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg Total
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily Total of all reporting groups
    Overall Participants 100 91 191
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51
    (12)
    53
    (11)
    52
    (11)
    Sex: Female, Male (Count of Participants)
    Female
    22
    22%
    27
    29.7%
    49
    25.7%
    Male
    78
    78%
    64
    70.3%
    142
    74.3%
    Race/Ethnicity, Customized (participants) [Number]
    Asian
    55
    55%
    49
    53.8%
    104
    54.5%
    White
    35
    35%
    28
    30.8%
    63
    33%
    Other
    5
    5%
    9
    9.9%
    14
    7.3%
    Black/African American
    5
    5%
    5
    5.5%
    10
    5.2%
    Region of Enrollment (participants) [Number]
    United States
    12
    12%
    9
    9.9%
    21
    11%
    Philippines
    4
    4%
    5
    5.5%
    9
    4.7%
    Taiwan
    11
    11%
    11
    12.1%
    22
    11.5%
    Hong Kong
    5
    5%
    5
    5.5%
    10
    5.2%
    Greece
    8
    8%
    5
    5.5%
    13
    6.8%
    Thailand
    10
    10%
    9
    9.9%
    19
    9.9%
    Indonesia
    2
    2%
    0
    0%
    2
    1%
    Turkey
    3
    3%
    1
    1.1%
    4
    2.1%
    Russian Federation
    1
    1%
    1
    1.1%
    2
    1%
    India
    15
    15%
    14
    15.4%
    29
    15.2%
    Canada
    5
    5%
    3
    3.3%
    8
    4.2%
    Brazil
    13
    13%
    13
    14.3%
    26
    13.6%
    Poland
    3
    3%
    5
    5.5%
    8
    4.2%
    Singapore
    3
    3%
    5
    5.5%
    8
    4.2%
    South Africa
    3
    3%
    4
    4.4%
    7
    3.7%
    France
    2
    2%
    0
    0%
    2
    1%
    United Kingdom
    0
    0%
    1
    1.1%
    1
    0.5%
    Child-Pugh Class (Number) [Number]
    Class A
    7
    7%
    10
    11%
    17
    8.9%
    Class B
    63
    63%
    61
    67%
    124
    64.9%
    Class C
    30
    30%
    20
    22%
    50
    26.2%
    Alanine Aminotransferase (ALT) (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    99.2
    (111.23)
    100.0
    (81.68)
    99.6
    (98.01)
    Child-Pugh Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    8.81
    (1.98)
    8.35
    (1.82)
    8.59
    (1.91)
    HBV DNA by PCR (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    7.53
    (1.829)
    8.16
    (2.179)
    7.83
    (2.023)
    Mayo End-Stage Liver Disease (MELD) score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    17.07
    (5.00)
    15.30
    (4.61)
    16.23
    (4.89)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24
    Description Mean reduction in serum HBV DNA determined by PCR assay (log10 copies/mL) at Week 24 adjusted for baseline HBV DNA and lamivudine resistance (LVDr) status, based on linear regression analysis.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized, modified intention-to-treat (ITT) efficacy data set. Includes on-treatment data (obtained after the start of therapy and no more than 5 days after the last dose of study therapy) collected for treated subjects. Includes those participants with PCR measurements in the Week 24 analysis window.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 76 73
    Mean (Standard Error) [log10 copies/mL]
    -4.48
    (0.200)
    -3.40
    (0.255)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Linear
    Comments Linear regression model adjusted for baseline HBV DNA and LVDr status.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.74
    Confidence Interval (2-Sided) 95%
    -2.30 to -1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in HBV DNA by PCR at Week 48
    Description Mean change from baseline in HBV DNA by PCR at Week 48, adjusted for baseline HBV DNA and LVDr Status.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized, modified intention-to-treat (ITT) efficacy data set. Includes on-treatment data (obtained after the start of therapy and no more than 5 days after the last dose of study therapy) collected for treated subjects. Includes those participants with PCR measurements in the Week 48 analysis window.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 69 61
    Mean (Standard Error) [log10 copies/mL]
    -4.66
    (0.204)
    -3.90
    (0.353)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Linear
    Comments adjusted for baseline HBV DNA and LVDr Status
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -1.85 to -0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24
    Description
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized population, responders only (non-completer=failure).
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Number [participants]
    49
    49%
    15
    16.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Mean Percent Difference
    Estimated Value 32.7
    Confidence Interval (2-Sided) 95%
    20.2 to 45.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48
    Description
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized population, responders only (non-completer=failure).
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Number [Participants]
    57
    57%
    18
    19.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Mean percent treatment difference
    Estimated Value 38
    Confidence Interval (2-Sided) 95%
    24.8 to 50.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48
    Description Number of participants in each group who achieved ALT normalization (≤1.0 x upper limit of normal [ULN]) among those with baseline ALT >1.0 x ULN at Weeks 24 and 48
    Time Frame Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized population, responders only (non-completer=failure).Participants in each group who achieved ALT normalization among those with baseline ALT >1.0 x ULN.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 78 71
    Week 24
    46
    46%
    28
    30.8%
    Week 48
    49
    49%
    33
    36.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Week 24 treatment difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0193
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter percent treatment difference
    Estimated Value 19.2
    Confidence Interval (2-Sided) 95%
    3.7 to 34.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Week 48 treatment difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0425
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter percent treatment difference
    Estimated Value 16.4
    Confidence Interval (2-Sided) 95%
    0.9 to 32.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Number of Subjects Achieving Composite Endpoint (HBV DNA < 10*4 Copies/mL by PCR Assay and Normal ALT [≤ 1.0 x ULN]) Through Week 48
    Description
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized, modified intention-to-treat (ITT) efficacy data set (includes on-treatment data collected for treated subjects. On-treatment data are those obtained after the start of therapy and no more than 5 days after the last dose of study therapy.) n=number of participants with measurement at baseline and timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline
    3
    3%
    1
    1.1%
    Week 4
    23
    23%
    6
    6.6%
    Week 8
    34
    34%
    11
    12.1%
    Week 12
    37
    37%
    16
    17.6%
    Week 24
    49
    49%
    24
    26.4%
    Week 48
    57
    57%
    34
    37.4%
    7. Secondary Outcome
    Title >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
    Description Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis).
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects-As-Randomized, modified intention-to-treat (ITT) efficacy data set (includes on-treatment data collected for treated subjects. On-treatment data are those obtained after start of therapy and <=5 days after the last dose of study therapy.) Non-completer=Failure. n=number of participants with measurement at baseline and timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline
    0
    0%
    0
    0%
    Week 4
    14
    14%
    11
    12.1%
    Week 8
    23
    23%
    10
    11%
    Week 12
    22
    22%
    11
    12.1%
    Week 24
    32
    32%
    22
    24.2%
    Week 36
    35
    35%
    19
    20.9%
    Week 48
    35
    35%
    25
    27.5%
    8. Secondary Outcome
    Title Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
    Description Number of participants in each group with improvement or no worsening in Child-Pugh score from baseline to Week 48 as measured by improvement or no worsening in Child-Pugh score. Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis).
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated participants (as-randomized). Non-completer=Failure. The modified intention-to-treat (ITT) efficacy data set included on-treatment data collected for treated subjects. On-treatment data are those obtained after the start of therapy and no more than 5 days after the last dose of study therapy.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline
    0
    0%
    0
    0%
    Week 4
    66
    66%
    67
    73.6%
    Week 8
    67
    67%
    62
    68.1%
    Week 12
    68
    68%
    62
    68.1%
    Week 24
    66
    66%
    65
    71.4%
    Week 48
    61
    61%
    61
    67%
    9. Secondary Outcome
    Title Change From Baseline in Child-Pugh Score Through Week 48
    Description Mean change from baseline in Child-Pugh score through week 48. Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis).
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized, modified intention-to-treat (ITT) efficacy data set (includes on-treatment data collected for treated subjects. On-treatment data are those obtained after the start of therapy and no more than 5 days after the last dose of study therapy.) n=number of participants with measurement at baseline and timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline Value (n=100, n=91)
    8.8
    (0.20)
    8.4
    (0.19)
    Change at Week 4 (n=90; n=85)
    -0.4
    (0.14)
    -0.3
    (0.14)
    Change at Week 8 (n=90; n=79)
    -0.4
    (0.18)
    -0.3
    (0.17)
    Change at Week 12 (n=87; n=80)
    -0.6
    (0.18)
    -0.3
    (0.15)
    Change at Week 24 (n=80; n=77)
    -1.2
    (0.20)
    -0.7
    (0.18)
    Change at Week 36 (n=75; n=70)
    -1.6
    (0.25)
    -0.9
    (0.18)
    Change at Week 48 (n=72; n=64)
    -1.7
    (0.26)
    -1.3
    (0.19)
    10. Secondary Outcome
    Title Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48
    Description Number of Participants in each group with improvement in Child-Pugh score from baseline to Week 48 as measured by improvement in Child-Pugh class. Improvement in Child-Pugh Class is defined as change from B to A or C to A. Evaluable subjects are subjects with Child-Pugh Class B or C at Baseline. Child-Pugh classification assesses the prognosis of chronic liver disease by 5 clinical measures, scored 1-3 each (most severe derangement=3). Score range: 5 (best prognosis) to 15 (worst prognosis). Child-Pugh class A to C employs the added score from above: 5-6=Class A; 7-9=Class B; 10-15=Class C.
    Time Frame Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated participants (as-randomized). The modified intention-to-treat (ITT) efficacy data set included on-treatment data collected for treated subjects. On-treatment data are those obtained after the start of therapy and no more than 5 days after the last dose of study therapy.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 93 81
    Week 24
    25
    25%
    22
    24.2%
    Week 48
    35
    35%
    29
    31.9%
    11. Secondary Outcome
    Title Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48
    Description Adjusted mean change from baseline in MELD score through Week 48 (adjusted for baseline value). The Model for End-Stage Liver Disease (MELD), is a scoring system for assessing the severity of chronic liver disease. MELD uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. In interpreting the MELD Score in hospitalized patients, the 3 month mortality is: 40 or more=100% mortality; 30-39=83% mortality; 20-29=76% mortality; 10-19=27% mortality; <10=4% mortality.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated participants - as-randomized populations; n=number of participants with assessment at baseline and timepoint. The modified intention-to-treat (ITT) efficacy data set included on-treatment data collected for treated subjects. On-treatment data are obtained after the start of therapy and <=5 days after the last dose of study therapy.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline Value (n=100; n=91)
    17.1
    (0.50)
    15.3
    (0.48)
    Week 4 (n=97; n=87)
    -0.1
    (0.38)
    0.1
    (0.25)
    Week 8 (n=90; n=79)
    -0.8
    (0.35)
    -0.4
    (0.34)
    Week 12 (n=88; n=80)
    -1.2
    (0.41)
    -0.9
    (0.32)
    Week 24 (n=80; n=77)
    -2.0
    (0.45)
    -0.9
    (0.46)
    Week 36 (n=75; n=70)
    -2.3
    (0.57)
    -1.2
    (0.48)
    Week 48 (n=72; n=62)
    -2.6
    (0.62)
    -1.7
    (0.50)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Covariate adjusted model for MELD score at Week 24
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.51
    Comments
    Method Regression, Linear
    Comments Model estimate incorporates prognostic factors measured at baseline. Adjusted for baseline
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.41
    Confidence Interval (2-Sided) 95%
    -1.63 to 0.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Covariate adjusted model for MELD score at Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Linear
    Comments Model estimate incorporates prognostic factors measured at baseline. Adjusted for baseline
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.59
    Confidence Interval (2-Sided) 95%
    -1.08 to 1.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Improvement or No Worsening in MELD Score Through Week 48
    Description Participants with improvement or no worsening (any decrease or no change from baseline in score) in MELD score through Week 48. The Model for End-Stage Liver Disease (MELD), is a scoring system for assessing the severity of chronic liver disease. MELD uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. In interpreting the MELD Score in hospitalized patients, the 3 month mortality is: 40 or more=100% mortality; 30-39=83% mortality; 20-29=76% mortality; 10-19=27% mortality; <10=4% mortality.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated Subjects - As-Randomized, modified intention-to-treat (ITT) efficacy data set (includes on-treatment data collected for treated subjects. On-treatment data are those obtained after the start of therapy and no more than 5 days after the last dose of study therapy.) n=number of participants with measurement at baseline and timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline
    0
    0%
    0
    0%
    Week 4
    58
    58%
    51
    56%
    Week 8
    63
    63%
    52
    57.1%
    Week 12
    67
    67%
    60
    65.9%
    Week 24
    62
    62%
    51
    56%
    Week 48
    53
    53%
    47
    51.6%
    13. Secondary Outcome
    Title Mean Changes From Baseline in Quality of Life as Measured by the Short Form 36 (SF-36)
    Description Scoring for the SF-36 will be done using the algorithm developed by the Research ANd Development(RAND) Corporation (a scale of 0-100). Higher scores represent better quality of life. Coding for items with 2-category responses=0 and 100; 3-category=0/50/100; 5-category=0/25/50/75/100; 6-category=0/20/40/60/80/100. Scores of items in the same scale are combined to create the 8 scale scores (physical functioning, role-physical, bodily-pain, general health, vitality, social functioning, role-emotional, mental health). Physical and mental health composite scores will be computed for the group.
    Time Frame Baseline, Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    This endpoint was not analyzed due to lack of complete data at 48 Weeks, but will be assessed at future time points.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 0 0
    14. Secondary Outcome
    Title Mean Changes From Baseline in Quality of Life, as Measured by EuroQol-5D (EQ-5D) at Weeks 24 and 48
    Description The EQ-5D has 5 attributes (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression), each with 3 levels (no problem, some problems, and major problems). This algorithm gives valuation (weights) to each of the 15 responses on the form. Each valuation is a negative number, subtracted from the maximum score of 1 (perfect well being). The overall health index score ranges from 0 (dead) to 1 (perfect health) value scale, and the visual analog scale ranges from 0 to 100. Item weights will be obtained from the EuroQol group.
    Time Frame Baseline, Week 24, Week 48

    Outcome Measure Data

    Analysis Population Description
    This endpoint was not analyzed due to lack of complete data at 48 Weeks, but will be assessed at future time points.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 0 0
    15. Secondary Outcome
    Title Change From Baseline in Albumin Through Week 48
    Description Mean albumin levels, and mean change from baseline in albumin, a measure of synthetic liver function. Normal range for albumin = 3.5 - 5.3 g/dL.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated participants - as randomized; n=number of participants with value at baseline and given timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline Value (n=100; n=91)
    3.00
    (0.55)
    3.10
    (0.067)
    Change at Week 4 (n=98; n=88)
    -0.04
    (0.032)
    -0.01
    (0.033)
    Change at Week 8 (n=92; n=82)
    0.01
    (0.034)
    -0.03
    (0.037)
    Change at Week 12 (n=88; n=80)
    0.05
    (0.039)
    0.03
    (0.037)
    Change at Week 24 (n=81; n=77)
    0.26
    (0.056)
    0.20
    (0.048)
    Change at Week 36 (n=76; n=70)
    0.36
    (0.062)
    0.25
    (0.052)
    Change at Week 48 (n=72; n=63)
    0.49
    (0.061)
    0.34
    (0.057)
    16. Secondary Outcome
    Title Mean Change From Baseline in Prothrombin Time Through Week 48
    Description Mean prothrombin time, and mean change from baseline in prothrombin time, a measure of synthetic liver function. Prothrombin time is the time it takes (in seconds) for a sample of blood to clot. Normal range for prothrombin time (PT) = 10-13 seconds.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated, as-randomized. Subjects with normal values at baseline were excluded from the analysis. n=number of participants with value at baseline and given timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline Value (n=100; n=91)
    16.28
    (0.234)
    15.35
    (0.196)
    Change at Week 4 (n=98; n=87)
    -0.08
    (0.156)
    0.03
    (0.114)
    Change at Week 8 (n=91; n=79)
    -0.10
    (0.158)
    0.06
    (0.161)
    Change at Week 12 (n=88; n=80)
    -0.29
    (0.153)
    -0.05
    (0.162)
    Change at Week 24 (n=80; n=77)
    -0.75
    (0.216)
    -0.18
    (0.205)
    Change at Week 48 (n=72; n=63)
    -0.99
    (0.288)
    -0.52
    (0.197)
    17. Secondary Outcome
    Title Mean Change From Baseline in Total Bilirubin Through Week 48
    Description Mean total bilirubin levels, and mean change from baseline in total bilirubin, a measure of liver secretory function.Normal range for total bilirubin = 0.2 - 1.2 mg/dL.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated, as-randomized. Subjects with normal values at baseline were excluded from the analysis. n=number of participants with value at baseline and given timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 100 91
    Baseline Value (n=100; n=91)
    2.80
    (0.207)
    2.50
    (0.214)
    Change at Week 4 (n=98; n=88)
    -0.06
    (0.154)
    0.21
    (0.172)
    Change at Week 8 (n=92; n=82)
    0.11
    (0.376)
    -0.17
    (0.094)
    Change at Week 12 (n=88;l n=80)
    -0.20
    (0.193)
    -0.28
    (0.109)
    Change at Week 24 (n=81; n=77)
    -0.41
    (0.154)
    -0.14
    (0.227)
    Change at Week 36 (n=76; n=70)
    -0.36
    (0.329)
    -0.09
    (0.298)
    Change at Week 48 (n=72; n=63)
    -0.61
    (0.233)
    -0.10
    (0.450)
    18. Secondary Outcome
    Title Change From Baseline in Platelet Count Through Week 48
    Description Mean baseline platelet count and mean change from baseline in platelet count at specific timepoints. Platelets are the smallest particles found in the blood, which play a major role in forming blood clots. Normal range for platelets = 140 - 450 X 10*9 c/L.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated, as-randomized. Subjects with normal values at baseline were excluded from the analysis. n=number of participants with value at baseline and given timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 97 91
    Baseline Value (n=97; n=91)
    87.32
    (4.771)
    93.31
    (4.947)
    Change at Week 4 (n=90; n=85)
    -0.93
    (2.064)
    -2.14
    (2.553)
    Change at Week 8 (n=82; n=76)
    3.55
    (3.063)
    3.88
    (2.923)
    Change at Week 12 (n=85; n=79)
    4.36
    (2.837)
    -0.81
    (2.814)
    Change at Week 24 (n=77; n=76)
    2.47
    (2.556)
    -2.89
    (3.205)
    Change at Week 36 (n=72; n=69)
    6.56
    (3.534)
    1.32
    (3.188)
    Change at Week 48 (n=68; n=63)
    10.19
    (4.956)
    3.05
    (3.570)
    19. Secondary Outcome
    Title Participants Achieving Albumin Normalization Through Week 48
    Description Number of participants who achieved normalization of albumin (>= 1 x lower limit of normal [LLN]), a measure of liver function, at specific timepoints.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated subjects (as randomized). Excludes subjects with normal albumin at Baseline. Non-completer = failure.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 82 69
    Baseline
    0
    0%
    0
    0%
    Week 4
    2
    2%
    7
    7.7%
    Week 8
    9
    9%
    6
    6.6%
    Week 12
    6
    6%
    11
    12.1%
    Week 24
    20
    20%
    14
    15.4%
    Week 36
    29
    29%
    14
    15.4%
    Week 48
    32
    32%
    20
    22%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Difference estimate ETV - ADV at Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference Estimate
    Estimated Value 10.4
    Confidence Interval (2-Sided) 95%
    -4.5 to 25.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    20. Secondary Outcome
    Title Participants Achieving Prothrombin Time Normalization Through Week 48
    Description Number of participants who achieved normalization of prothrombin time (<= 1 x ULN), a measure of liver function, at specific timepoints.
    Time Frame Baseline, Week4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 95 82
    Baseline
    0
    0%
    0
    0%
    Week 4
    3
    3%
    4
    4.4%
    Week 8
    5
    5%
    4
    4.4%
    Week 12
    4
    4%
    3
    3.3%
    Week 24
    9
    9%
    6
    6.6%
    Week 36
    10
    10%
    5
    5.5%
    Week 48
    8
    8%
    7
    7.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Difference Estimate at Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference Estimate
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -8.7 to 8.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Participants Achieving Total Bilirubin Normalization Through Week 48
    Description Number of participants who achieved normalization of total bilirubin (<= 1 x ULN), a measure of liver function, at specific timepoints.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 75 65
    Baseline
    0
    0%
    0
    0%
    Week 4
    4
    4%
    9
    9.9%
    Week 8
    10
    10%
    9
    9.9%
    Week 12
    8
    8%
    9
    9.9%
    Week 24
    12
    12%
    10
    11%
    Week 36
    9
    9%
    17
    18.7%
    Week 48
    15
    15%
    18
    19.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Difference Estimate at Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference Estimate
    Estimated Value -7.2
    Confidence Interval (2-Sided) 95%
    -21.3 to 6.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    22. Secondary Outcome
    Title Participants Achieving Platelet Count Normalization Through Week 48
    Description Number of participants who achieved normalization of platelet count (>= 1 x lower limit of normal [LLN]), a measure of liver function, at specific timepoints.
    Time Frame Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 85 76
    Baseline
    0
    0%
    0
    0%
    Week 4
    3
    3%
    4
    4.4%
    Week 8
    3
    3%
    5
    5.5%
    Week 12
    7
    7%
    3
    3.3%
    Week 24
    2
    2%
    2
    2.2%
    Week 36
    5
    5%
    2
    2.2%
    Week 48
    6
    6%
    1
    1.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments Difference Estimate at Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference Estimate
    Estimated Value 5.7
    Confidence Interval (2-Sided) 95%
    -0.3 to 11.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    23. Secondary Outcome
    Title Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
    Description HCC-free survival was analyzed using life tables. Measured values show the number of HCC events among treated participants at given time points.
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Treated, through Week 48 - (analyzed as-treated). (Week 48 on-treatment safety data contain all on-treatment data up to study Day 336, if the subject is still on treatment. If the subject discontinued before study Day 336, then all data up to 5 days after the discontinuation date were included.) n=number of participants at risk at each timepoint.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 102 89
    Weeks 0-4 (n=102; n=89)
    2
    3
    Weeks 4-8 (n=99; n=86)
    5
    5
    Weeks 8-12 (n=96; n=83)
    10
    6
    Weeks 12-16 (n=90; n=80)
    11
    9
    Weeks 16-20 (n=87; n=77)
    11
    11
    Weeks 20-24 (n=86; n=75)
    16
    14
    Weeks 24-28 (n=81; n=71)
    17
    15
    Weeks 28-32 (n=78; n=70)
    17
    17
    Weeks 32-36 (n=77; n=66)
    17
    18
    Weeks 36-40 (n=77; n=64)
    19
    20
    Weeks 40-44 (n=73; n=62)
    21
    20
    Weeks 44-48 (n=71; n=62)
    24
    22
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Entecavir (ETV) 1.0 mg, Adefovir (ADV) 10 mg
    Comments treatment comparison of HCC-free survival at Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.20
    Comments
    Method Regression, Cox
    Comments Cox proportional hazard model, adjusted for age <=45 versus age >45 years, gender, and race (white versus non-white).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.46 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Cumulative Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, HCC, Discontinuations Due to AEs, and Confirmed Creatinine Increase >=0.5 mg/dL
    Description AE=any new untoward medical occurrence/worsening of a pre-existing medical condition regardless of causal relationship. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires/prolongs inpatient hospitalization; results in persistent/significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. Confirmed increase in serum creatinine=values ≥0.5 mg/dL compared with baseline on 2 sequential measures.
    Time Frame on-treatment events obtained after the start of therapy and no more than 5 days after the last dose of study therapy.

    Outcome Measure Data

    Analysis Population Description
    As-treated population (all randomized subjects treated with at least 1 dose of study therapy, ETV or ADV, based on actual treatment received). Note that 5 additional enrolled participants died prior to initiation of treatment and are not included in this table.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 102 89
    Any AE
    91
    91%
    86
    94.5%
    Grade 3/4 AEs
    55
    55%
    42
    46.2%
    SAEs
    70
    70%
    59
    64.8%
    Deaths
    23
    23%
    29
    31.9%
    HCC
    12
    12%
    18
    19.8%
    Discontinuations due to AEs
    7
    7%
    5
    5.5%
    Confirmed creatinine increase >= 0.5 mg/dL
    17
    17%
    21
    23.1%
    25. Secondary Outcome
    Title Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
    Description Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 48 data set was used to evaluate the Week-48 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death.
    Time Frame Week 48=all on-treatment laboratory measurements up to Week 48. Cumulative data = on-treatment laboratory measurements obtained after the start of therapy and no more than 5 days after the last dose of study therapy.

    Outcome Measure Data

    Analysis Population Description
    As-treated population (all randomized subjects treated with at least 1 dose of study therapy, ETV or ADV, based on actual treatment received).
    Arm/Group Title Week 48 - Entecavir (ETV) 1.0 mg Week 48 - Adefovir (ADV) 10 mg Cumulative - Entecavir (ETV) 1.0 mg Cumulative - Adefovir (ADV) 10 mg
    Arm/Group Description
    Measure Participants 102 89 102 89
    Hemoglobin
    8
    8%
    8
    8.8%
    11
    5.8%
    10
    NaN
    International Normalized Ratio
    30
    30%
    22
    24.2%
    40
    20.9%
    32
    NaN
    Platelet Count
    20
    20%
    21
    23.1%
    25
    13.1%
    24
    NaN
    Prothrombin Time
    20
    20%
    7
    7.7%
    25
    13.1%
    11
    NaN
    Bicarbonate, Low
    3
    3%
    4
    4.4%
    4
    2.1%
    4
    NaN
    Chloride, Serum, Low
    2
    2%
    2
    2.2%
    2
    1%
    2
    NaN
    Bicarbonate/Carbon Dioxide, Low
    3
    3%
    4
    4.4%
    4
    2.1%
    4
    NaN
    Potassium, Serum, High
    1
    1%
    0
    0%
    1
    0.5%
    0
    NaN
    Sodium, Serum
    6
    6%
    3
    3.3%
    6
    3.1%
    5
    NaN
    Sodium, Serum, Low
    6
    6%
    3
    3.3%
    6
    3.1%
    5
    NaN
    Lipase, Total (colorimetric assay)
    17
    17%
    18
    19.8%
    23
    12%
    25
    NaN
    Alanine Aminotransferase (ALT)
    3
    3%
    1
    1.1%
    5
    2.6%
    4
    NaN
    Albumin
    9
    9%
    3
    3.3%
    9
    4.7%
    3
    NaN
    Alkaline Phosphatase (ALP)
    0
    0%
    1
    1.1%
    1
    0.5%
    1
    NaN
    Aspartate Aminotransferase (AST)
    7
    7%
    3
    3.3%
    9
    4.7%
    7
    NaN
    Bilirubin, Total
    19
    19%
    18
    19.8%
    24
    12.6%
    25
    NaN
    G-Glutamyl Transferase (GGT)
    1
    1%
    6
    6.6%
    9
    4.7%
    10
    NaN
    Glucose, Fasting Serum, High
    0
    0%
    0
    0%
    1
    0.5%
    0
    NaN
    Creatinine
    1
    1%
    0
    0%
    2
    1%
    0
    NaN
    Phosphorus, inorganic
    0
    0%
    4
    4.4%
    0
    0%
    6
    NaN
    Blood, urine
    13
    13%
    13
    14.3%
    18
    9.4%
    22
    NaN
    Glucose, urine
    11
    11%
    11
    12.1%
    17
    8.9%
    13
    NaN
    Protein, urine
    1
    1%
    2
    2.2%
    2
    1%
    4
    NaN
    Neutrophils (relative)
    0
    0%
    1
    1.1%
    0
    0%
    1
    NaN
    Neutrophils + Bands (relative)
    2
    2%
    4
    4.4%
    4
    2.1%
    8
    NaN
    Neutrophils (absolute)
    2
    2%
    3
    3.3%
    5
    2.6%
    7
    NaN
    26. Secondary Outcome
    Title Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment
    Description ALT flare=ALT > 2 x baseline and > 10 x upper limit of normal (ULN) by clinical laboratory evaluation. Table includes number of participants with selected clinical events and/or laboratory abnormalities during ALT flares. Selected clinical events during ALT flares=ascites, hepatic encephalopathy, jaundice, bacterial peritonitis. Selected Laboratory abnormalities during ALT flares=international normalized ratio > 1.5 or prothrombin time >= 1.2 x ULN and total bilirubin >2.5 mg/dL and > 1 mg/dL increase from baseline.
    Time Frame On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date.

    Outcome Measure Data

    Analysis Population Description
    Treated participants - as treated. The on-treatment safety data set contains data from all randomized subjects treated with at least 1 dose of study therapy, ETV or ADV. Treatment group for safety data set is based on actual treatment received.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 102 89
    ALT flares
    2
    2%
    1
    1.1%
    ALT flares, no clinical events/lab abnormalities
    1
    1%
    0
    0%
    ALT flares, with clinical events/lab abnormalities
    1
    1%
    1
    1.1%
    27. Secondary Outcome
    Title Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
    Description Data includes type of malignant neoplasm.
    Time Frame On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.

    Outcome Measure Data

    Analysis Population Description
    The on-treatment safety data set contains data from all randomized subjects treated with at least 1 dose of study therapy, ETV or ADV. Treatment group for safety data set is based on actual treatment received.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 102 89
    Any Adverse Events
    14
    14%
    18
    19.8%
    Hepatic Neoplasm, Malignant
    12
    12%
    18
    19.8%
    Basal Cell Carcinoma
    1
    1%
    0
    0%
    Lymph Node Cancer, Metastatic
    1
    1%
    0
    0%
    Hepatic Mass
    1
    1%
    0
    0%
    28. Secondary Outcome
    Title Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up
    Description
    Time Frame On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.

    Outcome Measure Data

    Analysis Population Description
    The on-treatment safety data set contains data from all randomized subjects treated with at least 1 dose of study therapy, ETV or ADV. Treatment group for safety data set is based on actual treatment received.
    Arm/Group Title Entecavir (ETV) 1.0 mg Adefovir (ADV) 10 mg
    Arm/Group Description Tablets, Oral, 1 mg once daily Tablets, Oral, 10 mg once daily
    Measure Participants 102 89
    Liver Transplant: Yes
    11
    11%
    3
    3.3%
    Liver Transplant: No
    91
    91%
    86
    94.5%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title ADEFOVIR ENTECAVIR
    Arm/Group Description
    All Cause Mortality
    ADEFOVIR ENTECAVIR
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    ADEFOVIR ENTECAVIR
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 59/89 (66.3%) 70/102 (68.6%)
    Blood and lymphatic system disorders
    ANAEMIA 0/89 (0%) 1/102 (1%)
    THROMBOCYTOPENIA 1/89 (1.1%) 1/102 (1%)
    Cardiac disorders
    PERICARDIAL EFFUSION 1/89 (1.1%) 1/102 (1%)
    VENTRICULAR TACHYCARDIA 1/89 (1.1%) 0/102 (0%)
    CARDIO-RESPIRATORY ARREST 0/89 (0%) 1/102 (1%)
    CARDIAC FAILURE CONGESTIVE 2/89 (2.2%) 0/102 (0%)
    ACUTE MYOCARDIAL INFARCTION 2/89 (2.2%) 0/102 (0%)
    Congenital, familial and genetic disorders
    EXOMPHALOS 0/89 (0%) 1/102 (1%)
    Ear and labyrinth disorders
    OTOTOXICITY 1/89 (1.1%) 0/102 (0%)
    Eye disorders
    CATARACT 0/89 (0%) 1/102 (1%)
    Gastrointestinal disorders
    ASCITES 4/89 (4.5%) 4/102 (3.9%)
    MELAENA 0/89 (0%) 1/102 (1%)
    VOMITING 1/89 (1.1%) 0/102 (0%)
    DIARRHOEA 0/89 (0%) 1/102 (1%)
    CONSTIPATION 1/89 (1.1%) 0/102 (0%)
    HAEMATEMESIS 0/89 (0%) 1/102 (1%)
    PANCREATITIS 0/89 (0%) 2/102 (2%)
    GASTRIC ULCER 0/89 (0%) 1/102 (1%)
    ABDOMINAL PAIN 1/89 (1.1%) 2/102 (2%)
    INGUINAL HERNIA 0/89 (0%) 2/102 (2%)
    ABDOMINAL HERNIA 0/89 (0%) 1/102 (1%)
    ANAL HAEMORRHAGE 0/89 (0%) 1/102 (1%)
    LEUKOPLAKIA ORAL 1/89 (1.1%) 0/102 (0%)
    RECTAL HAEMORRHAGE 1/89 (1.1%) 0/102 (0%)
    GASTRITIS ALCOHOLIC 1/89 (1.1%) 0/102 (0%)
    VARICES OESOPHAGEAL 0/89 (0%) 2/102 (2%)
    ABDOMINAL DISTENSION 0/89 (0%) 1/102 (1%)
    GASTRIC ULCER HAEMORRHAGE 0/89 (0%) 1/102 (1%)
    DUODENAL ULCER HAEMORRHAGE 1/89 (1.1%) 0/102 (0%)
    GASTRIC VARICES HAEMORRHAGE 1/89 (1.1%) 0/102 (0%)
    GASTROINTESTINAL HAEMORRHAGE 4/89 (4.5%) 0/102 (0%)
    OESOPHAGEAL VARICES HAEMORRHAGE 2/89 (2.2%) 4/102 (3.9%)
    PORTAL HYPERTENSIVE GASTROPATHY 1/89 (1.1%) 0/102 (0%)
    UPPER GASTROINTESTINAL HAEMORRHAGE 3/89 (3.4%) 4/102 (3.9%)
    DIVERTICULUM INTESTINAL HAEMORRHAGIC 0/89 (0%) 1/102 (1%)
    General disorders
    DEATH 0/89 (0%) 2/102 (2%)
    PYREXIA 3/89 (3.4%) 2/102 (2%)
    ASTHENIA 0/89 (0%) 1/102 (1%)
    CHEST PAIN 1/89 (1.1%) 0/102 (0%)
    SUDDEN DEATH 0/89 (0%) 1/102 (1%)
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME 0/89 (0%) 1/102 (1%)
    Hepatobiliary disorders
    JAUNDICE 1/89 (1.1%) 0/102 (0%)
    CHOLANGITIS 2/89 (2.2%) 0/102 (0%)
    HEPATIC MASS 0/89 (0%) 1/102 (1%)
    CHOLECYSTITIS 0/89 (0%) 1/102 (1%)
    CHOLELITHIASIS 0/89 (0%) 2/102 (2%)
    LIVER DISORDER 1/89 (1.1%) 1/102 (1%)
    HEPATIC FAILURE 2/89 (2.2%) 10/102 (9.8%)
    HEPATIC CIRRHOSIS 3/89 (3.4%) 3/102 (2.9%)
    BILE DUCT STENOSIS 1/89 (1.1%) 1/102 (1%)
    CHOLECYSTITIS ACUTE 0/89 (0%) 1/102 (1%)
    HYPERBILIRUBINAEMIA 2/89 (2.2%) 0/102 (0%)
    PORTAL HYPERTENSION 1/89 (1.1%) 0/102 (0%)
    HEPATORENAL SYNDROME 3/89 (3.4%) 3/102 (2.9%)
    ACUTE HEPATIC FAILURE 1/89 (1.1%) 0/102 (0%)
    HEPATITIS CHOLESTATIC 0/89 (0%) 1/102 (1%)
    CHRONIC HEPATIC FAILURE 0/89 (0%) 2/102 (2%)
    HEPATIC ARTERY THROMBOSIS 1/89 (1.1%) 0/102 (0%)
    HEPATIC FUNCTION ABNORMAL 2/89 (2.2%) 2/102 (2%)
    Immune system disorders
    TRANSPLANT REJECTION 0/89 (0%) 1/102 (1%)
    LIVER TRANSPLANT REJECTION 0/89 (0%) 1/102 (1%)
    Infections and infestations
    SEPSIS 3/89 (3.4%) 5/102 (4.9%)
    PNEUMONIA 2/89 (2.2%) 3/102 (2.9%)
    UROSEPSIS 0/89 (0%) 1/102 (1%)
    BRONCHITIS 0/89 (0%) 1/102 (1%)
    CELLULITIS 1/89 (1.1%) 3/102 (2.9%)
    BACTERAEMIA 1/89 (1.1%) 0/102 (0%)
    HEPATITIS B 1/89 (1.1%) 0/102 (0%)
    ANAL ABSCESS 0/89 (0%) 1/102 (1%)
    SEPTIC SHOCK 1/89 (1.1%) 4/102 (3.9%)
    GASTROENTERITIS 0/89 (0%) 2/102 (2%)
    SCROTAL INFECTION 1/89 (1.1%) 0/102 (0%)
    ESCHERICHIA SEPSIS 0/89 (0%) 1/102 (1%)
    TESTICULAR ABSCESS 0/89 (0%) 1/102 (1%)
    PERINEPHRIC ABSCESS 0/89 (0%) 1/102 (1%)
    NECROTISING FASCIITIS 0/89 (0%) 1/102 (1%)
    PERITONITIS BACTERIAL 6/89 (6.7%) 6/102 (5.9%)
    PULMONARY TUBERCULOSIS 2/89 (2.2%) 0/102 (0%)
    CHOLECYSTITIS INFECTIVE 0/89 (0%) 1/102 (1%)
    ESCHERICHIA BACTERAEMIA 1/89 (1.1%) 0/102 (0%)
    URINARY TRACT INFECTION 1/89 (1.1%) 0/102 (0%)
    PHARYNGITIS STREPTOCOCCAL 1/89 (1.1%) 0/102 (0%)
    STREPTOCOCCAL BACTERAEMIA 1/89 (1.1%) 0/102 (0%)
    GASTRIC ULCER HELICOBACTER 1/89 (1.1%) 0/102 (0%)
    LOWER RESPIRATORY TRACT INFECTION 0/89 (0%) 1/102 (1%)
    ESCHERICHIA URINARY TRACT INFECTION 0/89 (0%) 1/102 (1%)
    BETA HAEMOLYTIC STREPTOCOCCAL INFECTION 0/89 (0%) 1/102 (1%)
    Injury, poisoning and procedural complications
    OVERDOSE 1/89 (1.1%) 1/102 (1%)
    RADIUS FRACTURE 1/89 (1.1%) 0/102 (0%)
    INCISIONAL HERNIA 1/89 (1.1%) 1/102 (1%)
    TESTICULAR INJURY 0/89 (0%) 1/102 (1%)
    FOREIGN BODY TRAUMA 1/89 (1.1%) 0/102 (0%)
    Investigations
    HAEMOGLOBIN DECREASED 1/89 (1.1%) 0/102 (0%)
    BLOOD ALBUMIN DECREASED 2/89 (2.2%) 2/102 (2%)
    HEPATIC ENZYME INCREASED 1/89 (1.1%) 1/102 (1%)
    BLOOD BILIRUBIN INCREASED 6/89 (6.7%) 8/102 (7.8%)
    PROTHROMBIN TIME ABNORMAL 2/89 (2.2%) 3/102 (2.9%)
    BLOOD CREATININE INCREASED 1/89 (1.1%) 0/102 (0%)
    PROTHROMBIN TIME PROLONGED 13/89 (14.6%) 14/102 (13.7%)
    BLOOD BICARBONATE DECREASED 0/89 (0%) 2/102 (2%)
    ALANINE AMINOTRANSFERASE INCREASED 3/89 (3.4%) 3/102 (2.9%)
    ASPARTATE AMINOTRANSFERASE INCREASED 1/89 (1.1%) 0/102 (0%)
    INTERNATIONAL NORMALISED RATIO ABNORMAL 1/89 (1.1%) 2/102 (2%)
    INTERNATIONAL NORMALISED RATIO INCREASED 5/89 (5.6%) 5/102 (4.9%)
    Metabolism and nutrition disorders
    DEHYDRATION 1/89 (1.1%) 1/102 (1%)
    HYPOKALAEMIA 0/89 (0%) 1/102 (1%)
    HYPERKALAEMIA 0/89 (0%) 1/102 (1%)
    HYPONATRAEMIA 2/89 (2.2%) 3/102 (2.9%)
    FLUID OVERLOAD 1/89 (1.1%) 0/102 (0%)
    HYPOALBUMINAEMIA 0/89 (0%) 1/102 (1%)
    DIABETES MELLITUS 1/89 (1.1%) 1/102 (1%)
    ELECTROLYTE IMBALANCE 1/89 (1.1%) 1/102 (1%)
    Musculoskeletal and connective tissue disorders
    FASCIITIS 0/89 (0%) 1/102 (1%)
    MUSCLE SPASMS 0/89 (0%) 1/102 (1%)
    OSTEOARTHRITIS 1/89 (1.1%) 0/102 (0%)
    SPINAL COLUMN STENOSIS 0/89 (0%) 1/102 (1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    HEPATIC NEOPLASM MALIGNANT 15/89 (16.9%) 12/102 (11.8%)
    LYMPH NODE CANCER METASTATIC 0/89 (0%) 1/102 (1%)
    HEPATIC NEOPLASM MALIGNANT RECURRENT 0/89 (0%) 1/102 (1%)
    Nervous system disorders
    COMA HEPATIC 0/89 (0%) 1/102 (1%)
    HYDROCEPHALUS 1/89 (1.1%) 0/102 (0%)
    ENCEPHALOPATHY 3/89 (3.4%) 2/102 (2%)
    SENSORY DISTURBANCE 0/89 (0%) 1/102 (1%)
    HEPATIC ENCEPHALOPATHY 9/89 (10.1%) 10/102 (9.8%)
    CEREBROVASCULAR ACCIDENT 1/89 (1.1%) 0/102 (0%)
    SUBARACHNOID HAEMORRHAGE 1/89 (1.1%) 0/102 (0%)
    Renal and urinary disorders
    ANURIA 1/89 (1.1%) 0/102 (0%)
    OLIGURIA 0/89 (0%) 1/102 (1%)
    CALCULUS BLADDER 1/89 (1.1%) 0/102 (0%)
    RENAL IMPAIRMENT 1/89 (1.1%) 1/102 (1%)
    Reproductive system and breast disorders
    UTERINE HAEMORRHAGE 1/89 (1.1%) 0/102 (0%)
    BENIGN PROSTATIC HYPERPLASIA 0/89 (0%) 1/102 (1%)
    Respiratory, thoracic and mediastinal disorders
    HYPOXIA 0/89 (0%) 1/102 (1%)
    DYSPNOEA 0/89 (0%) 1/102 (1%)
    HAEMOPTYSIS 0/89 (0%) 1/102 (1%)
    HYDROTHORAX 0/89 (0%) 1/102 (1%)
    PLEURAL EFFUSION 3/89 (3.4%) 2/102 (2%)
    PULMONARY OEDEMA 0/89 (0%) 1/102 (1%)
    HEPATIC HYDROTHORAX 0/89 (0%) 1/102 (1%)
    RESPIRATORY FAILURE 0/89 (0%) 1/102 (1%)
    PNEUMONIA ASPIRATION 0/89 (0%) 1/102 (1%)
    ACUTE RESPIRATORY FAILURE 0/89 (0%) 1/102 (1%)
    ACUTE RESPIRATORY DISTRESS SYNDROME 0/89 (0%) 1/102 (1%)
    Social circumstances
    ALCOHOL USE 1/89 (1.1%) 0/102 (0%)
    Surgical and medical procedures
    CHOLECYSTECTOMY 1/89 (1.1%) 0/102 (0%)
    LIVER TRANSPLANT 0/89 (0%) 7/102 (6.9%)
    Vascular disorders
    BLEEDING VARICOSE VEIN 1/89 (1.1%) 1/102 (1%)
    CARDIOVASCULAR INSUFFICIENCY 0/89 (0%) 1/102 (1%)
    Other (Not Including Serious) Adverse Events
    ADEFOVIR ENTECAVIR
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 76/89 (85.4%) 77/102 (75.5%)
    Blood and lymphatic system disorders
    ANAEMIA 5/89 (5.6%) 6/102 (5.9%)
    Gastrointestinal disorders
    NAUSEA 4/89 (4.5%) 11/102 (10.8%)
    ASCITES 14/89 (15.7%) 14/102 (13.7%)
    VOMITING 8/89 (9%) 12/102 (11.8%)
    DIARRHOEA 18/89 (20.2%) 15/102 (14.7%)
    DYSPEPSIA 6/89 (6.7%) 10/102 (9.8%)
    TOOTHACHE 6/89 (6.7%) 3/102 (2.9%)
    CONSTIPATION 6/89 (6.7%) 9/102 (8.8%)
    ABDOMINAL PAIN 12/89 (13.5%) 14/102 (13.7%)
    DUODENAL ULCER 7/89 (7.9%) 3/102 (2.9%)
    GINGIVAL BLEEDING 2/89 (2.2%) 6/102 (5.9%)
    VARICES OESOPHAGEAL 6/89 (6.7%) 4/102 (3.9%)
    ABDOMINAL DISTENSION 7/89 (7.9%) 7/102 (6.9%)
    ABDOMINAL PAIN UPPER 9/89 (10.1%) 12/102 (11.8%)
    GASTROOESOPHAGEAL REFLUX DISEASE 5/89 (5.6%) 3/102 (2.9%)
    General disorders
    FATIGUE 13/89 (14.6%) 13/102 (12.7%)
    PYREXIA 16/89 (18%) 20/102 (19.6%)
    ASTHENIA 7/89 (7.9%) 7/102 (6.9%)
    CHEST PAIN 5/89 (5.6%) 5/102 (4.9%)
    OEDEMA PERIPHERAL 21/89 (23.6%) 18/102 (17.6%)
    Infections and infestations
    INFLUENZA 5/89 (5.6%) 8/102 (7.8%)
    PNEUMONIA 2/89 (2.2%) 7/102 (6.9%)
    CELLULITIS 5/89 (5.6%) 2/102 (2%)
    NASOPHARYNGITIS 9/89 (10.1%) 8/102 (7.8%)
    URINARY TRACT INFECTION 6/89 (6.7%) 7/102 (6.9%)
    UPPER RESPIRATORY TRACT INFECTION 14/89 (15.7%) 19/102 (18.6%)
    Metabolism and nutrition disorders
    ANOREXIA 5/89 (5.6%) 4/102 (3.9%)
    DIABETES MELLITUS 5/89 (5.6%) 5/102 (4.9%)
    Musculoskeletal and connective tissue disorders
    BACK PAIN 9/89 (10.1%) 8/102 (7.8%)
    ARTHRALGIA 7/89 (7.9%) 4/102 (3.9%)
    MUSCLE SPASMS 5/89 (5.6%) 9/102 (8.8%)
    Nervous system disorders
    HEADACHE 18/89 (20.2%) 7/102 (6.9%)
    DIZZINESS 9/89 (10.1%) 9/102 (8.8%)
    ENCEPHALOPATHY 1/89 (1.1%) 7/102 (6.9%)
    Psychiatric disorders
    INSOMNIA 8/89 (9%) 9/102 (8.8%)
    Renal and urinary disorders
    HAEMATURIA 7/89 (7.9%) 1/102 (1%)
    Reproductive system and breast disorders
    GYNAECOMASTIA 2/89 (2.2%) 10/102 (9.8%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 15/89 (16.9%) 17/102 (16.7%)
    DYSPNOEA 7/89 (7.9%) 5/102 (4.9%)
    EPISTAXIS 5/89 (5.6%) 9/102 (8.8%)
    Skin and subcutaneous tissue disorders
    PRURITUS 5/89 (5.6%) 7/102 (6.9%)
    Vascular disorders
    HYPERTENSION 4/89 (4.5%) 10/102 (9.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title BMS Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00065507
    Other Study ID Numbers:
    • AI463-048
    First Posted:
    Jul 29, 2003
    Last Update Posted:
    Jun 24, 2013
    Last Verified:
    Jun 1, 2013