Trial Outcomes & Findings for Comparison of Entecavir to Adefovir in Chronic Hepatitis B Virus (HBV) Patients With Hepatic Decompensation (NCT NCT00065507)
NCT ID: NCT00065507
Last Updated: 2013-06-24
Results Overview
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.
COMPLETED
PHASE3
195 participants
Baseline, Week 24
2013-06-24
Participant Flow
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).
Participant milestones
| Measure |
Entecavir (ETV) 1.0 mg
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
Tablets, Oral, 10 mg once daily
|
|---|---|---|
|
Overall Study
STARTED
|
100
|
91
|
|
Overall Study
Treated (As-Randomized Population)
|
100
|
91
|
|
Overall Study
Treated (As-Treated Population)
|
102
|
89
|
|
Overall Study
Treated, Wk 48 (As-Treated Population)
|
102
|
89
|
|
Overall Study
Treated, 24-Week Follow-Up Population
|
25
|
28
|
|
Overall Study
COMPLETED
|
71
|
62
|
|
Overall Study
NOT COMPLETED
|
29
|
29
|
Reasons for withdrawal
| Measure |
Entecavir (ETV) 1.0 mg
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
Tablets, Oral, 10 mg once daily
|
|---|---|---|
|
Overall Study
Death
|
16
|
17
|
|
Overall Study
Adverse Event
|
4
|
3
|
|
Overall Study
Lack of Efficacy
|
0
|
6
|
|
Overall Study
Poor/Non-compliance
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
|
Overall Study
Subject Withdrew Consent
|
2
|
1
|
|
Overall Study
Subject No Longer Meets Study Criteria
|
1
|
0
|
Baseline Characteristics
Comparison of Entecavir to Adefovir in Chronic Hepatitis B Virus (HBV) Patients With Hepatic Decompensation
Baseline characteristics by cohort
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Total
n=191 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race/Ethnicity, Customized
White
|
35 participants
n=5 Participants
|
28 participants
n=7 Participants
|
63 participants
n=5 Participants
|
|
Age Continuous
|
51 years
STANDARD_DEVIATION 12 • n=5 Participants
|
53 years
STANDARD_DEVIATION 11 • n=7 Participants
|
52 years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
78 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
55 participants
n=5 Participants
|
49 participants
n=7 Participants
|
104 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
5 participants
n=5 Participants
|
9 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
9 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
Philippines
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Region of Enrollment
Hong Kong
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Greece
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
10 participants
n=5 Participants
|
9 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Indonesia
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
India
|
15 participants
n=5 Participants
|
14 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
13 participants
n=5 Participants
|
13 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
France
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Child-Pugh Class
Class A
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Child-Pugh Class
Class B
|
63 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
124 Participants
n=5 Participants
|
|
Child-Pugh Class
Class C
|
30 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Alanine Aminotransferase (ALT)
|
99.2 U/L
STANDARD_DEVIATION 111.23 • n=5 Participants
|
100.0 U/L
STANDARD_DEVIATION 81.68 • n=7 Participants
|
99.6 U/L
STANDARD_DEVIATION 98.01 • n=5 Participants
|
|
Child-Pugh Score
|
8.81 units on a scale
STANDARD_DEVIATION 1.98 • n=5 Participants
|
8.35 units on a scale
STANDARD_DEVIATION 1.82 • n=7 Participants
|
8.59 units on a scale
STANDARD_DEVIATION 1.91 • n=5 Participants
|
|
HBV DNA by PCR
|
7.53 log10 copies/mL
STANDARD_DEVIATION 1.829 • n=5 Participants
|
8.16 log10 copies/mL
STANDARD_DEVIATION 2.179 • n=7 Participants
|
7.83 log10 copies/mL
STANDARD_DEVIATION 2.023 • n=5 Participants
|
|
Mayo End-Stage Liver Disease (MELD) score
|
17.07 units on a scale
STANDARD_DEVIATION 5.00 • n=5 Participants
|
15.30 units on a scale
STANDARD_DEVIATION 4.61 • n=7 Participants
|
16.23 units on a scale
STANDARD_DEVIATION 4.89 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=76 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=73 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 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 0.200
|
-3.40 log10 copies/mL
Standard Error 0.255
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: 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.
Mean change from baseline in HBV DNA by PCR at Week 48, adjusted for baseline HBV DNA and LVDr Status.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=69 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=61 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Change From Baseline in HBV DNA by PCR at Week 48
|
-4.66 log10 copies/mL
Standard Error 0.204
|
-3.90 log10 copies/mL
Standard Error 0.353
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: Treated Subjects - As-Randomized population, responders only (non-completer=failure).
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24
|
49 participants
|
15 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 48Population: Treated Subjects - As-Randomized population, responders only (non-completer=failure).
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48
|
57 Participants
|
18 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24, Week 48Population: 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.
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
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=78 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=71 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - 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
|
46 Participants
|
28 Participants
|
—
|
—
|
|
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
|
33 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48Population: 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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - 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
|
3 Participants
|
1 Participants
|
—
|
—
|
|
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
|
6 Participants
|
—
|
—
|
|
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
|
11 Participants
|
—
|
—
|
|
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
|
16 Participants
|
—
|
—
|
|
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
|
24 Participants
|
—
|
—
|
|
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
|
34 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: 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.
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).
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Week 4
|
14 Participants
|
11 Participants
|
—
|
—
|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Baseline
|
0 Participants
|
0 Participants
|
—
|
—
|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Week 8
|
23 Participants
|
10 Participants
|
—
|
—
|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Week 12
|
22 Participants
|
11 Participants
|
—
|
—
|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Week 24
|
32 Participants
|
22 Participants
|
—
|
—
|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Week 36
|
35 Participants
|
19 Participants
|
—
|
—
|
|
>=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
Week 48
|
35 Participants
|
25 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48Population: 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.
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).
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
Baseline
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
Week 4
|
66 Participants
|
67 Participants
|
—
|
—
|
|
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
Week 8
|
67 Participants
|
62 Participants
|
—
|
—
|
|
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
Week 12
|
68 Participants
|
62 Participants
|
—
|
—
|
|
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
Week 24
|
66 Participants
|
65 Participants
|
—
|
—
|
|
Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
Week 48
|
61 Participants
|
61 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: 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.
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).
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 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 0.20
|
-0.7 units on a scale
Standard Error 0.18
|
—
|
—
|
|
Change From Baseline in Child-Pugh Score Through Week 48
Baseline Value (n=100, n=91)
|
8.8 units on a scale
Standard Error 0.20
|
8.4 units on a scale
Standard Error 0.19
|
—
|
—
|
|
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
|
-0.3 units on a scale
Standard Error 0.14
|
—
|
—
|
|
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
|
-0.3 units on a scale
Standard Error 0.17
|
—
|
—
|
|
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
|
-0.3 units on a scale
Standard Error 0.15
|
—
|
—
|
|
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
|
-0.9 units on a scale
Standard Error 0.18
|
—
|
—
|
|
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
|
-1.3 units on a scale
Standard Error 0.19
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24, Week 48Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=93 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=81 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48
Week 24
|
25 Participants
|
22 Participants
|
—
|
—
|
|
Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48
Week 48
|
35 Participants
|
29 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - 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)
|
17.1 units on a scale
Standard Error 0.50
|
15.3 units on a scale
Standard Error 0.48
|
—
|
—
|
|
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
|
0.1 units on a scale
Standard Error 0.25
|
—
|
—
|
|
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
|
-0.4 units on a scale
Standard Error 0.34
|
—
|
—
|
|
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
|
-0.9 units on a scale
Standard Error 0.32
|
—
|
—
|
|
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
|
-0.9 units on a scale
Standard Error 0.46
|
—
|
—
|
|
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
|
-1.2 units on a scale
Standard Error 0.48
|
—
|
—
|
|
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
|
-1.7 units on a scale
Standard Error 0.50
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Improvement or No Worsening in MELD Score Through Week 48
Baseline
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Improvement or No Worsening in MELD Score Through Week 48
Week 4
|
58 Participants
|
51 Participants
|
—
|
—
|
|
Improvement or No Worsening in MELD Score Through Week 48
Week 8
|
63 Participants
|
52 Participants
|
—
|
—
|
|
Improvement or No Worsening in MELD Score Through Week 48
Week 12
|
67 Participants
|
60 Participants
|
—
|
—
|
|
Improvement or No Worsening in MELD Score Through Week 48
Week 24
|
62 Participants
|
51 Participants
|
—
|
—
|
|
Improvement or No Worsening in MELD Score Through Week 48
Week 48
|
53 Participants
|
47 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24, Week 48Population: This endpoint was not analyzed due to lack of complete data at 48 Weeks, but will be assessed at future time points.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 24, Week 48Population: This endpoint was not analyzed due to lack of complete data at 48 Weeks, but will be assessed at future time points.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: Treated participants - as randomized; n=number of participants with value at baseline and given timepoint.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Change From Baseline in Albumin Through Week 48
Baseline Value (n=100; n=91)
|
3.00 g/dL
Standard Error 0.55
|
3.10 g/dL
Standard Error 0.067
|
—
|
—
|
|
Change From Baseline in Albumin Through Week 48
Change at Week 4 (n=98; n=88)
|
-0.04 g/dL
Standard Error 0.032
|
-0.01 g/dL
Standard Error 0.033
|
—
|
—
|
|
Change From Baseline in Albumin Through Week 48
Change at Week 8 (n=92; n=82)
|
0.01 g/dL
Standard Error 0.034
|
-0.03 g/dL
Standard Error 0.037
|
—
|
—
|
|
Change From Baseline in Albumin Through Week 48
Change at Week 12 (n=88; n=80)
|
0.05 g/dL
Standard Error 0.039
|
0.03 g/dL
Standard Error 0.037
|
—
|
—
|
|
Change From Baseline in Albumin Through Week 48
Change at Week 24 (n=81; n=77)
|
0.26 g/dL
Standard Error 0.056
|
0.20 g/dL
Standard Error 0.048
|
—
|
—
|
|
Change From Baseline in Albumin Through Week 48
Change at Week 36 (n=76; n=70)
|
0.36 g/dL
Standard Error 0.062
|
0.25 g/dL
Standard Error 0.052
|
—
|
—
|
|
Change From Baseline in Albumin Through Week 48
Change at Week 48 (n=72; n=63)
|
0.49 g/dL
Standard Error 0.061
|
0.34 g/dL
Standard Error 0.057
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Mean Change From Baseline in Prothrombin Time Through Week 48
Baseline Value (n=100; n=91)
|
16.28 seconds
Standard Error 0.234
|
15.35 seconds
Standard Error 0.196
|
—
|
—
|
|
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
|
0.03 seconds
Standard Error 0.114
|
—
|
—
|
|
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
|
0.06 seconds
Standard Error 0.161
|
—
|
—
|
|
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
|
-0.05 seconds
Standard Error 0.162
|
—
|
—
|
|
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
|
-0.18 seconds
Standard Error 0.205
|
—
|
—
|
|
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
|
-0.52 seconds
Standard Error 0.197
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=100 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 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
|
2.50 mg/dL
Standard Error 0.214
|
—
|
—
|
|
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
|
0.21 mg/dL
Standard Error 0.172
|
—
|
—
|
|
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
|
-0.17 mg/dL
Standard Error 0.094
|
—
|
—
|
|
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
|
-0.28 mg/dL
Standard Error 0.109
|
—
|
—
|
|
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
|
-0.14 mg/dL
Standard Error 0.227
|
—
|
—
|
|
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
|
-0.09 mg/dL
Standard Error 0.298
|
—
|
—
|
|
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
|
-0.10 mg/dL
Standard Error 0.450
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=97 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=91 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 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
|
93.31 10*9 c/L
Standard Error 4.947
|
—
|
—
|
|
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
|
-2.14 10*9 c/L
Standard Error 2.553
|
—
|
—
|
|
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
|
3.88 10*9 c/L
Standard Error 2.923
|
—
|
—
|
|
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
|
-0.81 10*9 c/L
Standard Error 2.814
|
—
|
—
|
|
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
|
-2.89 10*9 c/L
Standard Error 3.205
|
—
|
—
|
|
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
|
1.32 10*9 c/L
Standard Error 3.188
|
—
|
—
|
|
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
|
3.05 10*9 c/L
Standard Error 3.570
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: Treated subjects (as randomized). Excludes subjects with normal albumin at Baseline. Non-completer = failure.
Number of participants who achieved normalization of albumin (\>= 1 x lower limit of normal \[LLN\]), a measure of liver function, at specific timepoints.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=82 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=69 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Participants Achieving Albumin Normalization Through Week 48
Baseline
|
0 participants
|
0 participants
|
—
|
—
|
|
Participants Achieving Albumin Normalization Through Week 48
Week 4
|
2 participants
|
7 participants
|
—
|
—
|
|
Participants Achieving Albumin Normalization Through Week 48
Week 8
|
9 participants
|
6 participants
|
—
|
—
|
|
Participants Achieving Albumin Normalization Through Week 48
Week 12
|
6 participants
|
11 participants
|
—
|
—
|
|
Participants Achieving Albumin Normalization Through Week 48
Week 24
|
20 participants
|
14 participants
|
—
|
—
|
|
Participants Achieving Albumin Normalization Through Week 48
Week 36
|
29 participants
|
14 participants
|
—
|
—
|
|
Participants Achieving Albumin Normalization Through Week 48
Week 48
|
32 participants
|
20 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week4, Week 8, Week 12, Week 24, Week 36, Week 48Population: Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
Number of participants who achieved normalization of prothrombin time (\<= 1 x ULN), a measure of liver function, at specific timepoints.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=95 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=82 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Baseline
|
0 participants
|
0 participants
|
—
|
—
|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Week 4
|
3 participants
|
4 participants
|
—
|
—
|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Week 8
|
5 participants
|
4 participants
|
—
|
—
|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Week 12
|
4 participants
|
3 participants
|
—
|
—
|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Week 24
|
9 participants
|
6 participants
|
—
|
—
|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Week 36
|
10 participants
|
5 participants
|
—
|
—
|
|
Participants Achieving Prothrombin Time Normalization Through Week 48
Week 48
|
8 participants
|
7 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
Number of participants who achieved normalization of total bilirubin (\<= 1 x ULN), a measure of liver function, at specific timepoints.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=75 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=65 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Baseline
|
0 participants
|
0 participants
|
—
|
—
|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Week 4
|
4 participants
|
9 participants
|
—
|
—
|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Week 8
|
10 participants
|
9 participants
|
—
|
—
|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Week 12
|
8 participants
|
9 participants
|
—
|
—
|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Week 24
|
12 participants
|
10 participants
|
—
|
—
|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Week 36
|
9 participants
|
17 participants
|
—
|
—
|
|
Participants Achieving Total Bilirubin Normalization Through Week 48
Week 48
|
15 participants
|
18 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48Population: Treated subjects - as-randomized. Excludes participants with normal prothrombin time at baseline. Non-completer = failure.
Number of participants who achieved normalization of platelet count (\>= 1 x lower limit of normal \[LLN\]), a measure of liver function, at specific timepoints.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=85 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=76 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Participants Achieving Platelet Count Normalization Through Week 48
Baseline
|
0 participants
|
0 participants
|
—
|
—
|
|
Participants Achieving Platelet Count Normalization Through Week 48
Week 4
|
3 participants
|
4 participants
|
—
|
—
|
|
Participants Achieving Platelet Count Normalization Through Week 48
Week 8
|
3 participants
|
5 participants
|
—
|
—
|
|
Participants Achieving Platelet Count Normalization Through Week 48
Week 12
|
7 participants
|
3 participants
|
—
|
—
|
|
Participants Achieving Platelet Count Normalization Through Week 48
Week 24
|
2 participants
|
2 participants
|
—
|
—
|
|
Participants Achieving Platelet Count Normalization Through Week 48
Week 36
|
5 participants
|
2 participants
|
—
|
—
|
|
Participants Achieving Platelet Count Normalization Through Week 48
Week 48
|
6 participants
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 48Population: 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.
HCC-free survival was analyzed using life tables. Measured values show the number of HCC events among treated participants at given time points.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=102 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=89 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 0-4 (n=102; n=89)
|
2 HCC events
|
3 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 4-8 (n=99; n=86)
|
5 HCC events
|
5 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 8-12 (n=96; n=83)
|
10 HCC events
|
6 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 12-16 (n=90; n=80)
|
11 HCC events
|
9 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 16-20 (n=87; n=77)
|
11 HCC events
|
11 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 20-24 (n=86; n=75)
|
16 HCC events
|
14 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 24-28 (n=81; n=71)
|
17 HCC events
|
15 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 28-32 (n=78; n=70)
|
17 HCC events
|
17 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 32-36 (n=77; n=66)
|
17 HCC events
|
18 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 36-40 (n=77; n=64)
|
19 HCC events
|
20 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 40-44 (n=73; n=62)
|
21 HCC events
|
20 HCC events
|
—
|
—
|
|
Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
Weeks 44-48 (n=71; n=62)
|
24 HCC events
|
22 HCC events
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=102 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=89 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - 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
|
91 participants
|
86 participants
|
—
|
—
|
|
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
|
42 participants
|
—
|
—
|
|
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
|
59 participants
|
—
|
—
|
|
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
|
29 participants
|
—
|
—
|
|
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
|
18 participants
|
—
|
—
|
|
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
|
5 participants
|
—
|
—
|
|
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
|
21 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=102 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=89 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
n=102 Participants
|
Cumulative - Adefovir (ADV) 10 mg
n=89 Participants
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Hemoglobin
|
8 participants
|
8 participants
|
11 participants
|
10 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
International Normalized Ratio
|
30 participants
|
22 participants
|
40 participants
|
32 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Platelet Count
|
20 participants
|
21 participants
|
25 participants
|
24 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Prothrombin Time
|
20 participants
|
7 participants
|
25 participants
|
11 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Bicarbonate, Low
|
3 participants
|
4 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Chloride, Serum, Low
|
2 participants
|
2 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Bicarbonate/Carbon Dioxide, Low
|
3 participants
|
4 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Potassium, Serum, High
|
1 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Sodium, Serum
|
6 participants
|
3 participants
|
6 participants
|
5 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Sodium, Serum, Low
|
6 participants
|
3 participants
|
6 participants
|
5 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Lipase, Total (colorimetric assay)
|
17 participants
|
18 participants
|
23 participants
|
25 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Alanine Aminotransferase (ALT)
|
3 participants
|
1 participants
|
5 participants
|
4 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Albumin
|
9 participants
|
3 participants
|
9 participants
|
3 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Alkaline Phosphatase (ALP)
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Aspartate Aminotransferase (AST)
|
7 participants
|
3 participants
|
9 participants
|
7 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Bilirubin, Total
|
19 participants
|
18 participants
|
24 participants
|
25 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
G-Glutamyl Transferase (GGT)
|
1 participants
|
6 participants
|
9 participants
|
10 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Glucose, Fasting Serum, High
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Creatinine
|
1 participants
|
0 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Phosphorus, inorganic
|
0 participants
|
4 participants
|
0 participants
|
6 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Blood, urine
|
13 participants
|
13 participants
|
18 participants
|
22 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Glucose, urine
|
11 participants
|
11 participants
|
17 participants
|
13 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Protein, urine
|
1 participants
|
2 participants
|
2 participants
|
4 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Neutrophils (relative)
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Neutrophils + Bands (relative)
|
2 participants
|
4 participants
|
4 participants
|
8 participants
|
|
Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
Neutrophils (absolute)
|
2 participants
|
3 participants
|
5 participants
|
7 participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=102 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=89 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment
ALT flares
|
2 participants
|
1 participants
|
—
|
—
|
|
Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment
ALT flares, no clinical events/lab abnormalities
|
1 participants
|
0 participants
|
—
|
—
|
|
Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment
ALT flares, with clinical events/lab abnormalities
|
1 participants
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
Data includes type of malignant neoplasm.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=102 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=89 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
Any Adverse Events
|
14 participants
|
18 participants
|
—
|
—
|
|
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
Hepatic Neoplasm, Malignant
|
12 participants
|
18 participants
|
—
|
—
|
|
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
Basal Cell Carcinoma
|
1 participants
|
0 participants
|
—
|
—
|
|
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
Lymph Node Cancer, Metastatic
|
1 participants
|
0 participants
|
—
|
—
|
|
Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
Hepatic Mass
|
1 participants
|
0 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Entecavir (ETV) 1.0 mg
n=102 Participants
Tablets, Oral, 1 mg once daily
|
Adefovir (ADV) 10 mg
n=89 Participants
Tablets, Oral, 10 mg once daily
|
Cumulative - Entecavir (ETV) 1.0 mg
|
Cumulative - Adefovir (ADV) 10 mg
|
|---|---|---|---|---|
|
Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up
Liver Transplant: Yes
|
11 participants
|
3 participants
|
—
|
—
|
|
Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up
Liver Transplant: No
|
91 participants
|
86 participants
|
—
|
—
|
Adverse Events
ADEFOVIR
ENTECAVIR
Serious adverse events
| Measure |
ADEFOVIR
n=89 participants at risk
|
ENTECAVIR
n=102 participants at risk
|
|---|---|---|
|
Eye disorders
CATARACT
|
0.00%
0/89
|
0.98%
1/102
|
|
Investigations
HAEMOGLOBIN DECREASED
|
1.1%
1/89
|
0.00%
0/102
|
|
Investigations
BLOOD ALBUMIN DECREASED
|
2.2%
2/89
|
2.0%
2/102
|
|
Investigations
HEPATIC ENZYME INCREASED
|
1.1%
1/89
|
0.98%
1/102
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
6.7%
6/89
|
7.8%
8/102
|
|
Investigations
PROTHROMBIN TIME ABNORMAL
|
2.2%
2/89
|
2.9%
3/102
|
|
Investigations
BLOOD CREATININE INCREASED
|
1.1%
1/89
|
0.00%
0/102
|
|
Investigations
PROTHROMBIN TIME PROLONGED
|
14.6%
13/89
|
13.7%
14/102
|
|
Investigations
BLOOD BICARBONATE DECREASED
|
0.00%
0/89
|
2.0%
2/102
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
3.4%
3/89
|
2.9%
3/102
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
1.1%
1/89
|
0.00%
0/102
|
|
Investigations
INTERNATIONAL NORMALISED RATIO ABNORMAL
|
1.1%
1/89
|
2.0%
2/102
|
|
Investigations
INTERNATIONAL NORMALISED RATIO INCREASED
|
5.6%
5/89
|
4.9%
5/102
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
1.1%
1/89
|
0.98%
1/102
|
|
Cardiac disorders
VENTRICULAR TACHYCARDIA
|
1.1%
1/89
|
0.00%
0/102
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.00%
0/89
|
0.98%
1/102
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
2.2%
2/89
|
0.00%
0/102
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
2.2%
2/89
|
0.00%
0/102
|
|
Vascular disorders
BLEEDING VARICOSE VEIN
|
1.1%
1/89
|
0.98%
1/102
|
|
Vascular disorders
CARDIOVASCULAR INSUFFICIENCY
|
0.00%
0/89
|
0.98%
1/102
|
|
Social circumstances
ALCOHOL USE
|
1.1%
1/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
JAUNDICE
|
1.1%
1/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
CHOLANGITIS
|
2.2%
2/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
HEPATIC MASS
|
0.00%
0/89
|
0.98%
1/102
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.00%
0/89
|
2.0%
2/102
|
|
Hepatobiliary disorders
LIVER DISORDER
|
1.1%
1/89
|
0.98%
1/102
|
|
Hepatobiliary disorders
HEPATIC FAILURE
|
2.2%
2/89
|
9.8%
10/102
|
|
Hepatobiliary disorders
HEPATIC CIRRHOSIS
|
3.4%
3/89
|
2.9%
3/102
|
|
Hepatobiliary disorders
BILE DUCT STENOSIS
|
1.1%
1/89
|
0.98%
1/102
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.00%
0/89
|
0.98%
1/102
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
2.2%
2/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
PORTAL HYPERTENSION
|
1.1%
1/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
HEPATORENAL SYNDROME
|
3.4%
3/89
|
2.9%
3/102
|
|
Hepatobiliary disorders
ACUTE HEPATIC FAILURE
|
1.1%
1/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
HEPATITIS CHOLESTATIC
|
0.00%
0/89
|
0.98%
1/102
|
|
Hepatobiliary disorders
CHRONIC HEPATIC FAILURE
|
0.00%
0/89
|
2.0%
2/102
|
|
Hepatobiliary disorders
HEPATIC ARTERY THROMBOSIS
|
1.1%
1/89
|
0.00%
0/102
|
|
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
|
2.2%
2/89
|
2.0%
2/102
|
|
Immune system disorders
TRANSPLANT REJECTION
|
0.00%
0/89
|
0.98%
1/102
|
|
Immune system disorders
LIVER TRANSPLANT REJECTION
|
0.00%
0/89
|
0.98%
1/102
|
|
Nervous system disorders
COMA HEPATIC
|
0.00%
0/89
|
0.98%
1/102
|
|
Nervous system disorders
HYDROCEPHALUS
|
1.1%
1/89
|
0.00%
0/102
|
|
Nervous system disorders
ENCEPHALOPATHY
|
3.4%
3/89
|
2.0%
2/102
|
|
Nervous system disorders
SENSORY DISTURBANCE
|
0.00%
0/89
|
0.98%
1/102
|
|
Nervous system disorders
HEPATIC ENCEPHALOPATHY
|
10.1%
9/89
|
9.8%
10/102
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
1.1%
1/89
|
0.00%
0/102
|
|
Nervous system disorders
SUBARACHNOID HAEMORRHAGE
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
ASCITES
|
4.5%
4/89
|
3.9%
4/102
|
|
Gastrointestinal disorders
MELAENA
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
VOMITING
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
CONSTIPATION
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
HAEMATEMESIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.00%
0/89
|
2.0%
2/102
|
|
Gastrointestinal disorders
GASTRIC ULCER
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
1.1%
1/89
|
2.0%
2/102
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/89
|
2.0%
2/102
|
|
Gastrointestinal disorders
ABDOMINAL HERNIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
ANAL HAEMORRHAGE
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
LEUKOPLAKIA ORAL
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
RECTAL HAEMORRHAGE
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
GASTRITIS ALCOHOLIC
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
VARICES OESOPHAGEAL
|
0.00%
0/89
|
2.0%
2/102
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
GASTRIC ULCER HAEMORRHAGE
|
0.00%
0/89
|
0.98%
1/102
|
|
Gastrointestinal disorders
DUODENAL ULCER HAEMORRHAGE
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
GASTRIC VARICES HAEMORRHAGE
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
4.5%
4/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
OESOPHAGEAL VARICES HAEMORRHAGE
|
2.2%
2/89
|
3.9%
4/102
|
|
Gastrointestinal disorders
PORTAL HYPERTENSIVE GASTROPATHY
|
1.1%
1/89
|
0.00%
0/102
|
|
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
|
3.4%
3/89
|
3.9%
4/102
|
|
Gastrointestinal disorders
DIVERTICULUM INTESTINAL HAEMORRHAGIC
|
0.00%
0/89
|
0.98%
1/102
|
|
Ear and labyrinth disorders
OTOTOXICITY
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
SEPSIS
|
3.4%
3/89
|
4.9%
5/102
|
|
Infections and infestations
PNEUMONIA
|
2.2%
2/89
|
2.9%
3/102
|
|
Infections and infestations
UROSEPSIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
BRONCHITIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
CELLULITIS
|
1.1%
1/89
|
2.9%
3/102
|
|
Infections and infestations
BACTERAEMIA
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
HEPATITIS B
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
ANAL ABSCESS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
SEPTIC SHOCK
|
1.1%
1/89
|
3.9%
4/102
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/89
|
2.0%
2/102
|
|
Infections and infestations
SCROTAL INFECTION
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
ESCHERICHIA SEPSIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
TESTICULAR ABSCESS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
PERINEPHRIC ABSCESS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
NECROTISING FASCIITIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
PERITONITIS BACTERIAL
|
6.7%
6/89
|
5.9%
6/102
|
|
Infections and infestations
PULMONARY TUBERCULOSIS
|
2.2%
2/89
|
0.00%
0/102
|
|
Infections and infestations
CHOLECYSTITIS INFECTIVE
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
ESCHERICHIA BACTERAEMIA
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
URINARY TRACT INFECTION
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
PHARYNGITIS STREPTOCOCCAL
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
STREPTOCOCCAL BACTERAEMIA
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
GASTRIC ULCER HELICOBACTER
|
1.1%
1/89
|
0.00%
0/102
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
ESCHERICHIA URINARY TRACT INFECTION
|
0.00%
0/89
|
0.98%
1/102
|
|
Infections and infestations
BETA HAEMOLYTIC STREPTOCOCCAL INFECTION
|
0.00%
0/89
|
0.98%
1/102
|
|
Renal and urinary disorders
ANURIA
|
1.1%
1/89
|
0.00%
0/102
|
|
Renal and urinary disorders
OLIGURIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Renal and urinary disorders
CALCULUS BLADDER
|
1.1%
1/89
|
0.00%
0/102
|
|
Renal and urinary disorders
RENAL IMPAIRMENT
|
1.1%
1/89
|
0.98%
1/102
|
|
Surgical and medical procedures
CHOLECYSTECTOMY
|
1.1%
1/89
|
0.00%
0/102
|
|
Surgical and medical procedures
LIVER TRANSPLANT
|
0.00%
0/89
|
6.9%
7/102
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
1.1%
1/89
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
2.2%
2/89
|
2.9%
3/102
|
|
Metabolism and nutrition disorders
FLUID OVERLOAD
|
1.1%
1/89
|
0.00%
0/102
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
1.1%
1/89
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
ELECTROLYTE IMBALANCE
|
1.1%
1/89
|
0.98%
1/102
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
1.1%
1/89
|
0.98%
1/102
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
1.1%
1/89
|
0.00%
0/102
|
|
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Congenital, familial and genetic disorders
EXOMPHALOS
|
0.00%
0/89
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
OVERDOSE
|
1.1%
1/89
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
RADIUS FRACTURE
|
1.1%
1/89
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
INCISIONAL HERNIA
|
1.1%
1/89
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
TESTICULAR INJURY
|
0.00%
0/89
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
FOREIGN BODY TRAUMA
|
1.1%
1/89
|
0.00%
0/102
|
|
Musculoskeletal and connective tissue disorders
FASCIITIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
0.00%
0/89
|
0.98%
1/102
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
1.1%
1/89
|
0.00%
0/102
|
|
Musculoskeletal and connective tissue disorders
SPINAL COLUMN STENOSIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
HYDROTHORAX
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
3.4%
3/89
|
2.0%
2/102
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
HEPATIC HYDROTHORAX
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.00%
0/89
|
0.98%
1/102
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME
|
0.00%
0/89
|
0.98%
1/102
|
|
General disorders
DEATH
|
0.00%
0/89
|
2.0%
2/102
|
|
General disorders
PYREXIA
|
3.4%
3/89
|
2.0%
2/102
|
|
General disorders
ASTHENIA
|
0.00%
0/89
|
0.98%
1/102
|
|
General disorders
CHEST PAIN
|
1.1%
1/89
|
0.00%
0/102
|
|
General disorders
SUDDEN DEATH
|
0.00%
0/89
|
0.98%
1/102
|
|
General disorders
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
|
0.00%
0/89
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC NEOPLASM MALIGNANT
|
16.9%
15/89
|
11.8%
12/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LYMPH NODE CANCER METASTATIC
|
0.00%
0/89
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC NEOPLASM MALIGNANT RECURRENT
|
0.00%
0/89
|
0.98%
1/102
|
Other adverse events
| Measure |
ADEFOVIR
n=89 participants at risk
|
ENTECAVIR
n=102 participants at risk
|
|---|---|---|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
15.7%
14/89
|
18.6%
19/102
|
|
Renal and urinary disorders
HAEMATURIA
|
7.9%
7/89
|
0.98%
1/102
|
|
Vascular disorders
HYPERTENSION
|
4.5%
4/89
|
9.8%
10/102
|
|
Psychiatric disorders
INSOMNIA
|
9.0%
8/89
|
8.8%
9/102
|
|
Nervous system disorders
HEADACHE
|
20.2%
18/89
|
6.9%
7/102
|
|
Nervous system disorders
DIZZINESS
|
10.1%
9/89
|
8.8%
9/102
|
|
Nervous system disorders
ENCEPHALOPATHY
|
1.1%
1/89
|
6.9%
7/102
|
|
Gastrointestinal disorders
NAUSEA
|
4.5%
4/89
|
10.8%
11/102
|
|
Gastrointestinal disorders
ASCITES
|
15.7%
14/89
|
13.7%
14/102
|
|
Gastrointestinal disorders
VOMITING
|
9.0%
8/89
|
11.8%
12/102
|
|
Gastrointestinal disorders
DIARRHOEA
|
20.2%
18/89
|
14.7%
15/102
|
|
Gastrointestinal disorders
DYSPEPSIA
|
6.7%
6/89
|
9.8%
10/102
|
|
Gastrointestinal disorders
TOOTHACHE
|
6.7%
6/89
|
2.9%
3/102
|
|
Gastrointestinal disorders
CONSTIPATION
|
6.7%
6/89
|
8.8%
9/102
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
13.5%
12/89
|
13.7%
14/102
|
|
Gastrointestinal disorders
DUODENAL ULCER
|
7.9%
7/89
|
2.9%
3/102
|
|
Gastrointestinal disorders
GINGIVAL BLEEDING
|
2.2%
2/89
|
5.9%
6/102
|
|
Gastrointestinal disorders
VARICES OESOPHAGEAL
|
6.7%
6/89
|
3.9%
4/102
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
7.9%
7/89
|
6.9%
7/102
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
10.1%
9/89
|
11.8%
12/102
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
5.6%
5/89
|
2.9%
3/102
|
|
Infections and infestations
INFLUENZA
|
5.6%
5/89
|
7.8%
8/102
|
|
Infections and infestations
PNEUMONIA
|
2.2%
2/89
|
6.9%
7/102
|
|
Infections and infestations
CELLULITIS
|
5.6%
5/89
|
2.0%
2/102
|
|
Infections and infestations
NASOPHARYNGITIS
|
10.1%
9/89
|
7.8%
8/102
|
|
Infections and infestations
URINARY TRACT INFECTION
|
6.7%
6/89
|
6.9%
7/102
|
|
Metabolism and nutrition disorders
ANOREXIA
|
5.6%
5/89
|
3.9%
4/102
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
5.6%
5/89
|
4.9%
5/102
|
|
Blood and lymphatic system disorders
ANAEMIA
|
5.6%
5/89
|
5.9%
6/102
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
5.6%
5/89
|
6.9%
7/102
|
|
Reproductive system and breast disorders
GYNAECOMASTIA
|
2.2%
2/89
|
9.8%
10/102
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
10.1%
9/89
|
7.8%
8/102
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
7.9%
7/89
|
3.9%
4/102
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
5.6%
5/89
|
8.8%
9/102
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
16.9%
15/89
|
16.7%
17/102
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
7.9%
7/89
|
4.9%
5/102
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
5.6%
5/89
|
8.8%
9/102
|
|
General disorders
FATIGUE
|
14.6%
13/89
|
12.7%
13/102
|
|
General disorders
PYREXIA
|
18.0%
16/89
|
19.6%
20/102
|
|
General disorders
ASTHENIA
|
7.9%
7/89
|
6.9%
7/102
|
|
General disorders
CHEST PAIN
|
5.6%
5/89
|
4.9%
5/102
|
|
General disorders
OEDEMA PERIPHERAL
|
23.6%
21/89
|
17.6%
18/102
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER