Hepatitis B
Conditions
Keywords
hepatic decompensation
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.
Interventions
DRUGEntecavir (ETV)
Tablets, Oral, 1 mg once daily, 96 weeks from the time the last patient is randomized
DRUGAdefovir (ADV)
Tablets, Oral, 10 mg, once daily, 96 weeks from the time the last patient is randomized
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24 | Week 24 | — |
| Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48 | Week 48 | — |
| 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 |
| 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 | — |
| >=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). |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. | — |
| 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. |
Countries
Brazil, Canada, France, Greece, Hong Kong, India, Indonesia, Philippines, Poland, Russia, Singapore, South Africa, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Entecavir (ETV) 1.0 mg Tablets, Oral, 1 mg once daily | 100 |
| Adefovir (ADV) 10 mg Tablets, Oral, 10 mg once daily | 91 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Death | 16 | 17 |
| Overall Study | Lack of Efficacy | 0 | 6 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Poor/Non-compliance | 3 | 2 |
| Overall Study | Subject No Longer Meets Study Criteria | 1 | 0 |
| Overall Study | Subject Withdrew Consent | 2 | 1 |
Baseline characteristics
| Characteristic | Adefovir (ADV) 10 mg | Entecavir (ETV) 1.0 mg | Total |
|---|---|---|---|
| Age Continuous | 53 years STANDARD_DEVIATION 11 | 51 years STANDARD_DEVIATION 12 | 52 years STANDARD_DEVIATION 11 |
| Alanine Aminotransferase (ALT) | 100.0 U/L STANDARD_DEVIATION 81.68 | 99.2 U/L STANDARD_DEVIATION 111.23 | 99.6 U/L STANDARD_DEVIATION 98.01 |
| Child-Pugh Class Class A | 10 Participants | 7 Participants | 17 Participants |
| Child-Pugh Class Class B | 61 Participants | 63 Participants | 124 Participants |
| Child-Pugh Class Class C | 20 Participants | 30 Participants | 50 Participants |
| Child-Pugh Score | 8.35 units on a scale STANDARD_DEVIATION 1.82 | 8.81 units on a scale STANDARD_DEVIATION 1.98 | 8.59 units on a scale STANDARD_DEVIATION 1.91 |
| HBV DNA by PCR | 8.16 log10 copies/mL STANDARD_DEVIATION 2.179 | 7.53 log10 copies/mL STANDARD_DEVIATION 1.829 | 7.83 log10 copies/mL STANDARD_DEVIATION 2.023 |
| Mayo End-Stage Liver Disease (MELD) score | 15.30 units on a scale STANDARD_DEVIATION 4.61 | 17.07 units on a scale STANDARD_DEVIATION 5 | 16.23 units on a scale STANDARD_DEVIATION 4.89 |
| Race/Ethnicity, Customized Asian | 49 participants | 55 participants | 104 participants |
| Race/Ethnicity, Customized Black/African American | 5 participants | 5 participants | 10 participants |
| Race/Ethnicity, Customized Other | 9 participants | 5 participants | 14 participants |
| Race/Ethnicity, Customized White | 28 participants | 35 participants | 63 participants |
| Region of Enrollment Brazil | 13 participants | 13 participants | 26 participants |
| Region of Enrollment Canada | 3 participants | 5 participants | 8 participants |
| Region of Enrollment France | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Greece | 5 participants | 8 participants | 13 participants |
| Region of Enrollment Hong Kong | 5 participants | 5 participants | 10 participants |
| Region of Enrollment India | 14 participants | 15 participants | 29 participants |
| Region of Enrollment Indonesia | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Philippines | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Poland | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Russian Federation | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Singapore | 5 participants | 3 participants | 8 participants |
| Region of Enrollment South Africa | 4 participants | 3 participants | 7 participants |
| Region of Enrollment Taiwan | 11 participants | 11 participants | 22 participants |
| Region of Enrollment Thailand | 9 participants | 10 participants | 19 participants |
| Region of Enrollment Turkey | 1 participants | 3 participants | 4 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 9 participants | 12 participants | 21 participants |
| Sex: Female, Male Female | 27 Participants | 22 Participants | 49 Participants |
| Sex: Female, Male Male | 64 Participants | 78 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 76 / 89 | 77 / 102 |
| serious Total, serious adverse events | 59 / 89 | 70 / 102 |
Outcome results
Primary
Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at 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.
Time frame: Baseline, Week 24
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24 | -4.48 log10 copies/mL | Standard Error 0.2 |
| Adefovir (ADV) 10 mg | Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24 | -3.40 log10 copies/mL | Standard Error 0.255 |
p-value: <0.000195% CI: [-2.3, -1.18]Regression, Linear
Secondary
>=2-Point Reduction 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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 8 | 23 Participants |
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 24 | 32 Participants |
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 4 | 14 Participants |
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 36 | 35 Participants |
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 12 | 22 Participants |
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 48 | 35 Participants |
| Entecavir (ETV) 1.0 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Baseline | 0 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 48 | 25 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Baseline | 0 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 4 | 11 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 8 | 10 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 12 | 11 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 24 | 22 Participants |
| Adefovir (ADV) 10 mg | >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48 | Week 36 | 19 Participants |
Secondary
Change From Baseline in Albumin Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: Treated participants - as randomized; n=number of participants with value at baseline and given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 8 (n=92; n=82) | 0.01 g/dL | Standard Error 0.034 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 24 (n=81; n=77) | 0.26 g/dL | Standard Error 0.056 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 4 (n=98; n=88) | -0.04 g/dL | Standard Error 0.032 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 36 (n=76; n=70) | 0.36 g/dL | Standard Error 0.062 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 12 (n=88; n=80) | 0.05 g/dL | Standard Error 0.039 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 48 (n=72; n=63) | 0.49 g/dL | Standard Error 0.061 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Albumin Through Week 48 | Baseline Value (n=100; n=91) | 3.00 g/dL | Standard Error 0.55 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 48 (n=72; n=63) | 0.34 g/dL | Standard Error 0.057 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Baseline Value (n=100; n=91) | 3.10 g/dL | Standard Error 0.067 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 4 (n=98; n=88) | -0.01 g/dL | Standard Error 0.033 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 8 (n=92; n=82) | -0.03 g/dL | Standard Error 0.037 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 12 (n=88; n=80) | 0.03 g/dL | Standard Error 0.037 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 24 (n=81; n=77) | 0.20 g/dL | Standard Error 0.048 |
| Adefovir (ADV) 10 mg | Change From Baseline in Albumin Through Week 48 | Change at Week 36 (n=76; n=70) | 0.25 g/dL | Standard Error 0.052 |
Secondary
Change From Baseline in Child-Pugh Score Through 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).
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 12 (n=87; n=80) | -0.6 units on a scale | Standard Error 0.18 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Baseline Value (n=100, n=91) | 8.8 units on a scale | Standard Error 0.2 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 24 (n=80; n=77) | -1.2 units on a scale | Standard Error 0.2 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 8 (n=90; n=79) | -0.4 units on a scale | Standard Error 0.18 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 36 (n=75; n=70) | -1.6 units on a scale | Standard Error 0.25 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 48 (n=72; n=64) | -1.7 units on a scale | Standard Error 0.26 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 4 (n=90; n=85) | -0.4 units on a scale | Standard Error 0.14 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 48 (n=72; n=64) | -1.3 units on a scale | Standard Error 0.19 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Baseline Value (n=100, n=91) | 8.4 units on a scale | Standard Error 0.19 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 4 (n=90; n=85) | -0.3 units on a scale | Standard Error 0.14 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 8 (n=90; n=79) | -0.3 units on a scale | Standard Error 0.17 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 12 (n=87; n=80) | -0.3 units on a scale | Standard Error 0.15 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 24 (n=80; n=77) | -0.7 units on a scale | Standard Error 0.18 |
| Adefovir (ADV) 10 mg | Change From Baseline in Child-Pugh Score Through Week 48 | Change at Week 36 (n=75; n=70) | -0.9 units on a scale | Standard Error 0.18 |
Secondary
Change From Baseline in HBV DNA by PCR at Week 48
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Change From Baseline in HBV DNA by PCR at Week 48 | -4.66 log10 copies/mL | Standard Error 0.204 |
| Adefovir (ADV) 10 mg | Change From Baseline in HBV DNA by PCR at Week 48 | -3.90 log10 copies/mL | Standard Error 0.353 |
p-value: <0.000195% CI: [-1.85, -0.96]Regression, Linear
Secondary
Change From Baseline in Platelet Count Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 8 (n=82; n=76) | 3.55 10*9 c/L | Standard Error 3.063 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 24 (n=77; n=76) | 2.47 10*9 c/L | Standard Error 2.556 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 4 (n=90; n=85) | -0.93 10*9 c/L | Standard Error 2.064 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 36 (n=72; n=69) | 6.56 10*9 c/L | Standard Error 3.534 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 12 (n=85; n=79) | 4.36 10*9 c/L | Standard Error 2.837 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 48 (n=68; n=63) | 10.19 10*9 c/L | Standard Error 4.956 |
| Entecavir (ETV) 1.0 mg | Change From Baseline in Platelet Count Through Week 48 | Baseline Value (n=97; n=91) | 87.32 10*9 c/L | Standard Error 4.771 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 48 (n=68; n=63) | 3.05 10*9 c/L | Standard Error 3.57 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Baseline Value (n=97; n=91) | 93.31 10*9 c/L | Standard Error 4.947 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 4 (n=90; n=85) | -2.14 10*9 c/L | Standard Error 2.553 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 8 (n=82; n=76) | 3.88 10*9 c/L | Standard Error 2.923 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 12 (n=85; n=79) | -0.81 10*9 c/L | Standard Error 2.814 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 24 (n=77; n=76) | -2.89 10*9 c/L | Standard Error 3.205 |
| Adefovir (ADV) 10 mg | Change From Baseline in Platelet Count Through Week 48 | Change at Week 36 (n=72; n=69) | 1.32 10*9 c/L | Standard Error 3.188 |
Secondary
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
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.
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | 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 | SAEs | 70 participants |
| Entecavir (ETV) 1.0 mg | 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 | HCC | 12 participants |
| Entecavir (ETV) 1.0 mg | 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 | Grade 3/4 AEs | 55 participants |
| Entecavir (ETV) 1.0 mg | 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 | Discontinuations due to AEs | 7 participants |
| Entecavir (ETV) 1.0 mg | 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 | Deaths | 23 participants |
| Entecavir (ETV) 1.0 mg | 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 | Confirmed creatinine increase >= 0.5 mg/dL | 17 participants |
| Entecavir (ETV) 1.0 mg | 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 | Any AE | 91 participants |
| Adefovir (ADV) 10 mg | 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 | Confirmed creatinine increase >= 0.5 mg/dL | 21 participants |
| Adefovir (ADV) 10 mg | 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 | Any AE | 86 participants |
| Adefovir (ADV) 10 mg | 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 | Grade 3/4 AEs | 42 participants |
| Adefovir (ADV) 10 mg | 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 | SAEs | 59 participants |
| Adefovir (ADV) 10 mg | 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 | Deaths | 29 participants |
| Adefovir (ADV) 10 mg | 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 | HCC | 18 participants |
| Adefovir (ADV) 10 mg | 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 | Discontinuations due to AEs | 5 participants |
Secondary
Improvement or No Worsening in MELD Score Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Improvement or No Worsening in MELD Score Through Week 48 | Baseline | 0 Participants |
| Entecavir (ETV) 1.0 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 4 | 58 Participants |
| Entecavir (ETV) 1.0 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 8 | 63 Participants |
| Entecavir (ETV) 1.0 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 12 | 67 Participants |
| Entecavir (ETV) 1.0 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 24 | 62 Participants |
| Entecavir (ETV) 1.0 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 48 | 53 Participants |
| Adefovir (ADV) 10 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 24 | 51 Participants |
| Adefovir (ADV) 10 mg | Improvement or No Worsening in MELD Score Through Week 48 | Baseline | 0 Participants |
| Adefovir (ADV) 10 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 12 | 60 Participants |
| Adefovir (ADV) 10 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 4 | 51 Participants |
| Adefovir (ADV) 10 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 48 | 47 Participants |
| Adefovir (ADV) 10 mg | Improvement or No Worsening in MELD Score Through Week 48 | Week 8 | 52 Participants |
Secondary
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 8 (n=90; n=79) | -0.8 units on a scale | Standard Error 0.35 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 24 (n=80; n=77) | -2.0 units on a scale | Standard Error 0.45 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 4 (n=97; n=87) | -0.1 units on a scale | Standard Error 0.38 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 36 (n=75; n=70) | -2.3 units on a scale | Standard Error 0.57 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 12 (n=88; n=80) | -1.2 units on a scale | Standard Error 0.41 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 48 (n=72; n=62) | -2.6 units on a scale | Standard Error 0.62 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Baseline Value (n=100; n=91) | 17.1 units on a scale | Standard Error 0.5 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 48 (n=72; n=62) | -1.7 units on a scale | Standard Error 0.5 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Baseline Value (n=100; n=91) | 15.3 units on a scale | Standard Error 0.48 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 4 (n=97; n=87) | 0.1 units on a scale | Standard Error 0.25 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 8 (n=90; n=79) | -0.4 units on a scale | Standard Error 0.34 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 12 (n=88; n=80) | -0.9 units on a scale | Standard Error 0.32 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 24 (n=80; n=77) | -0.9 units on a scale | Standard Error 0.46 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48 | Week 36 (n=75; n=70) | -1.2 units on a scale | Standard Error 0.48 |
Comparison: Covariate adjusted model for MELD score at Week 24p-value: 0.5195% CI: [-1.63, 0.82]Regression, Linear
Comparison: Covariate adjusted model for MELD score at Week 48p-value: <0.000195% CI: [-1.08, 1.88]Regression, Linear
Secondary
Mean Change From Baseline in Prothrombin Time Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Baseline Value (n=100; n=91) | 16.28 seconds | Standard Error 0.234 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 4 (n=98; n=87) | -0.08 seconds | Standard Error 0.156 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 8 (n=91; n=79) | -0.10 seconds | Standard Error 0.158 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 12 (n=88; n=80) | -0.29 seconds | Standard Error 0.153 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 24 (n=80; n=77) | -0.75 seconds | Standard Error 0.216 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 48 (n=72; n=63) | -0.99 seconds | Standard Error 0.288 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 24 (n=80; n=77) | -0.18 seconds | Standard Error 0.205 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Baseline Value (n=100; n=91) | 15.35 seconds | Standard Error 0.196 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 12 (n=88; n=80) | -0.05 seconds | Standard Error 0.162 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 4 (n=98; n=87) | 0.03 seconds | Standard Error 0.114 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 48 (n=72; n=63) | -0.52 seconds | Standard Error 0.197 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Prothrombin Time Through Week 48 | Change at Week 8 (n=91; n=79) | 0.06 seconds | Standard Error 0.161 |
Secondary
Mean Change From Baseline in Total Bilirubin Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 8 (n=92; n=82) | 0.11 mg/dL | Standard Error 0.376 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 24 (n=81; n=77) | -0.41 mg/dL | Standard Error 0.154 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 4 (n=98; n=88) | -0.06 mg/dL | Standard Error 0.154 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 36 (n=76; n=70) | -0.36 mg/dL | Standard Error 0.329 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 12 (n=88;l n=80) | -0.20 mg/dL | Standard Error 0.193 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 48 (n=72; n=63) | -0.61 mg/dL | Standard Error 0.233 |
| Entecavir (ETV) 1.0 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Baseline Value (n=100; n=91) | 2.80 mg/dL | Standard Error 0.207 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 48 (n=72; n=63) | -0.10 mg/dL | Standard Error 0.45 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Baseline Value (n=100; n=91) | 2.50 mg/dL | Standard Error 0.214 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 4 (n=98; n=88) | 0.21 mg/dL | Standard Error 0.172 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 8 (n=92; n=82) | -0.17 mg/dL | Standard Error 0.094 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 12 (n=88;l n=80) | -0.28 mg/dL | Standard Error 0.109 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 24 (n=81; n=77) | -0.14 mg/dL | Standard Error 0.227 |
| Adefovir (ADV) 10 mg | Mean Change From Baseline in Total Bilirubin Through Week 48 | Change at Week 36 (n=76; n=70) | -0.09 mg/dL | Standard Error 0.298 |
Secondary
Mean Changes From Baseline in Quality of Life, as Measured by EuroQol-5D (EQ-5D) at Weeks 24 and 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.
Time frame: Baseline, Week 24, Week 48
Population: This endpoint was not analyzed due to lack of complete data at 48 Weeks, but will be assessed at future time points.
Secondary
Mean Changes From Baseline in Quality of Life as Measured by the Short Form 36 (SF-36)
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
Population: This endpoint was not analyzed due to lack of complete data at 48 Weeks, but will be assessed at future time points.
Secondary
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through 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.
Time frame: Week 48
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 16-20 (n=87; n=77) | 11 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 4-8 (n=99; n=86) | 5 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 20-24 (n=86; n=75) | 16 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 28-32 (n=78; n=70) | 17 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 32-36 (n=77; n=66) | 17 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 8-12 (n=96; n=83) | 10 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 36-40 (n=77; n=64) | 19 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 0-4 (n=102; n=89) | 2 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 40-44 (n=73; n=62) | 21 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 12-16 (n=90; n=80) | 11 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 44-48 (n=71; n=62) | 24 HCC events |
| Entecavir (ETV) 1.0 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 24-28 (n=81; n=71) | 17 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 44-48 (n=71; n=62) | 22 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 24-28 (n=81; n=71) | 15 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 0-4 (n=102; n=89) | 3 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 4-8 (n=99; n=86) | 5 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 8-12 (n=96; n=83) | 6 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 12-16 (n=90; n=80) | 9 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 16-20 (n=87; n=77) | 11 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 28-32 (n=78; n=70) | 17 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 32-36 (n=77; n=66) | 18 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 36-40 (n=77; n=64) | 20 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 40-44 (n=73; n=62) | 20 HCC events |
| Adefovir (ADV) 10 mg | Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48 | Weeks 20-24 (n=86; n=75) | 14 HCC events |
Comparison: treatment comparison of HCC-free survival at Week 48p-value: 0.295% CI: [0.46, 1.18]Regression, Cox
Secondary
Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 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
Time frame: Week 24, Week 48
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48 | Week 24 | 46 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48 | Week 48 | 49 Participants |
| Adefovir (ADV) 10 mg | Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48 | Week 24 | 28 Participants |
| Adefovir (ADV) 10 mg | Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48 | Week 48 | 33 Participants |
Comparison: Week 24 treatment differencep-value: 0.019395% CI: [3.7, 34.6]Cochran-Mantel-Haenszel
Comparison: Week 48 treatment differencep-value: 0.042595% CI: [0.9, 32]Cochran-Mantel-Haenszel
Secondary
Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up
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.
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up | Liver Transplant: Yes | 11 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up | Liver Transplant: No | 91 participants |
| Adefovir (ADV) 10 mg | Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up | Liver Transplant: Yes | 3 participants |
| Adefovir (ADV) 10 mg | Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up | Liver Transplant: No | 86 participants |
Secondary
Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment
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.
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment | ALT flares | 2 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment | ALT flares, no clinical events/lab abnormalities | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment | ALT flares, with clinical events/lab abnormalities | 1 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment | ALT flares | 1 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment | ALT flares, no clinical events/lab abnormalities | 0 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment | ALT flares, with clinical events/lab abnormalities | 1 participants |
Secondary
Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24
Time frame: Week 24
Population: Treated Subjects - As-Randomized population, responders only (non-completer=failure).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24 | 49 participants |
| Adefovir (ADV) 10 mg | Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24 | 15 participants |
p-value: <0.000195% CI: [20.2, 45.2]Cochran-Mantel-Haenszel
Secondary
Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48
Time frame: Week 48
Population: Treated Subjects - As-Randomized population, responders only (non-completer=failure).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48 | 57 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48 | 18 Participants |
p-value: <0.000195% CI: [24.8, 50.3]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Improvement in Child-Pugh Class at Week 24 and 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.
Time frame: Week 24, Week 48
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48 | Week 24 | 25 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48 | Week 48 | 35 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48 | Week 24 | 22 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48 | Week 48 | 29 Participants |
Secondary
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to 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).
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Baseline | 0 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 4 | 66 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 8 | 67 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 12 | 68 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 24 | 66 Participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 48 | 61 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 24 | 65 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Baseline | 0 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 12 | 62 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 4 | 67 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 48 | 61 Participants |
| Adefovir (ADV) 10 mg | Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48 | Week 8 | 62 Participants |
Secondary
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
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.
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Hepatic Neoplasm, Malignant | 12 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Lymph Node Cancer, Metastatic | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Basal Cell Carcinoma | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Hepatic Mass | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Any Adverse Events | 14 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Hepatic Mass | 0 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Any Adverse Events | 18 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Hepatic Neoplasm, Malignant | 18 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Basal Cell Carcinoma | 0 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period | Lymph Node Cancer, Metastatic | 0 participants |
Secondary
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
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.
Population: As-treated population (all randomized subjects treated with at least 1 dose of study therapy, ETV or ADV, based on actual treatment received).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate, Low | 3 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alkaline Phosphatase (ALP) | 0 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Creatinine | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Protein, urine | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Chloride, Serum, Low | 2 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, Fasting Serum, High | 0 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Albumin | 9 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | G-Glutamyl Transferase (GGT) | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate/Carbon Dioxide, Low | 3 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Aspartate Aminotransferase (AST) | 7 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Platelet Count | 20 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, urine | 11 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Potassium, Serum, High | 1 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils + Bands (relative) | 2 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Phosphorus, inorganic | 0 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (absolute) | 2 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum | 6 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (relative) | 0 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Hemoglobin | 8 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Blood, urine | 13 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum, Low | 6 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Prothrombin Time | 20 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alanine Aminotransferase (ALT) | 3 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bilirubin, Total | 19 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Lipase, Total (colorimetric assay) | 17 participants |
| Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | International Normalized Ratio | 30 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Lipase, Total (colorimetric assay) | 18 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alanine Aminotransferase (ALT) | 1 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (absolute) | 3 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, Fasting Serum, High | 0 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Albumin | 3 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alkaline Phosphatase (ALP) | 1 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Aspartate Aminotransferase (AST) | 3 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | International Normalized Ratio | 22 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bilirubin, Total | 18 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | G-Glutamyl Transferase (GGT) | 6 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (relative) | 1 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Platelet Count | 21 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Prothrombin Time | 7 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Protein, urine | 2 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate, Low | 4 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Chloride, Serum, Low | 2 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, urine | 11 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate/Carbon Dioxide, Low | 4 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils + Bands (relative) | 4 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Potassium, Serum, High | 0 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Blood, urine | 13 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum | 3 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum, Low | 3 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Hemoglobin | 8 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Phosphorus, inorganic | 4 participants |
| Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Creatinine | 0 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Protein, urine | 2 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Creatinine | 2 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Hemoglobin | 11 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | International Normalized Ratio | 40 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Platelet Count | 25 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Prothrombin Time | 25 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate, Low | 4 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Chloride, Serum, Low | 2 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate/Carbon Dioxide, Low | 4 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Potassium, Serum, High | 1 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum | 6 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum, Low | 6 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alanine Aminotransferase (ALT) | 5 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Albumin | 9 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alkaline Phosphatase (ALP) | 1 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Aspartate Aminotransferase (AST) | 9 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bilirubin, Total | 24 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | G-Glutamyl Transferase (GGT) | 9 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, Fasting Serum, High | 1 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Phosphorus, inorganic | 0 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Blood, urine | 18 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, urine | 17 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Lipase, Total (colorimetric assay) | 23 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (relative) | 0 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils + Bands (relative) | 4 participants |
| Cumulative - Entecavir (ETV) 1.0 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (absolute) | 5 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Creatinine | 0 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Phosphorus, inorganic | 6 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum | 5 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Potassium, Serum, High | 0 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (absolute) | 7 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Blood, urine | 22 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate/Carbon Dioxide, Low | 4 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Chloride, Serum, Low | 2 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils + Bands (relative) | 8 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, urine | 13 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bicarbonate, Low | 4 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Prothrombin Time | 11 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Aspartate Aminotransferase (AST) | 7 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Protein, urine | 4 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Platelet Count | 24 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | International Normalized Ratio | 32 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Albumin | 3 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Bilirubin, Total | 25 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Neutrophils (relative) | 1 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | G-Glutamyl Transferase (GGT) | 10 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alkaline Phosphatase (ALP) | 1 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Alanine Aminotransferase (ALT) | 4 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Hemoglobin | 10 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Glucose, Fasting Serum, High | 0 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Lipase, Total (colorimetric assay) | 25 participants |
| Cumulative - Adefovir (ADV) 10 mg | Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data | Sodium, Serum, Low | 5 participants |
Secondary
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
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | 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 | 3 Participants |
| Entecavir (ETV) 1.0 mg | 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 | Week 4 | 23 Participants |
| Entecavir (ETV) 1.0 mg | 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 | Week 8 | 34 Participants |
| Entecavir (ETV) 1.0 mg | 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 | Week 12 | 37 Participants |
| Entecavir (ETV) 1.0 mg | 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 | Week 24 | 49 Participants |
| Entecavir (ETV) 1.0 mg | 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 | Week 48 | 57 Participants |
| Adefovir (ADV) 10 mg | 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 | Week 24 | 24 Participants |
| Adefovir (ADV) 10 mg | 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 | 1 Participants |
| Adefovir (ADV) 10 mg | 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 | Week 12 | 16 Participants |
| Adefovir (ADV) 10 mg | 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 | Week 4 | 6 Participants |
| Adefovir (ADV) 10 mg | 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 | Week 48 | 34 Participants |
| Adefovir (ADV) 10 mg | 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 | Week 8 | 11 Participants |
Secondary
Participants Achieving Albumin Normalization Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: Treated subjects (as randomized). Excludes subjects with normal albumin at Baseline. Non-completer = failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 8 | 9 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 24 | 20 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 4 | 2 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 36 | 29 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 12 | 6 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 48 | 32 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Albumin Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 48 | 20 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 4 | 7 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 8 | 6 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 12 | 11 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 24 | 14 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Albumin Normalization Through Week 48 | Week 36 | 14 participants |
Comparison: Difference estimate ETV - ADV at Week 4895% CI: [-4.5, 25.2]
Secondary
Participants Achieving Platelet Count Normalization Through 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.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Population: Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 8 | 3 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 24 | 2 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 4 | 3 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 36 | 5 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 12 | 7 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 48 | 6 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 48 | 1 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 4 | 4 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 8 | 5 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 12 | 3 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 24 | 2 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Platelet Count Normalization Through Week 48 | Week 36 | 2 participants |
Comparison: Difference Estimate at Week 4895% CI: [-0.3, 11.7]
Secondary
Participants Achieving Prothrombin Time Normalization Through Week 48
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
Population: Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 8 | 5 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 24 | 9 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 4 | 3 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 36 | 10 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 12 | 4 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 48 | 8 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 48 | 7 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 4 | 4 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 8 | 4 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 12 | 3 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 24 | 6 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Prothrombin Time Normalization Through Week 48 | Week 36 | 5 participants |
Comparison: Difference Estimate at Week 4895% CI: [-8.7, 8]
Secondary
Participants Achieving Total Bilirubin Normalization Through Week 48
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
Population: Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 8 | 10 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 24 | 12 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 4 | 4 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 36 | 9 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 12 | 8 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 48 | 15 participants |
| Entecavir (ETV) 1.0 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 48 | 18 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Baseline | 0 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 4 | 9 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 8 | 9 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 12 | 9 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 24 | 10 participants |
| Adefovir (ADV) 10 mg | Participants Achieving Total Bilirubin Normalization Through Week 48 | Week 36 | 17 participants |
Comparison: Difference Estimate at Week 4895% CI: [-21.3, 6.9]