Trial Outcomes & Findings for Study Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease. (NCT NCT00298363)
NCT ID: NCT00298363
Last Updated: 2013-04-25
Results Overview
Tolerability failure was defined as permanent discontinuation of study drug due to a treatment-emergent adverse event (AE), including any subject who temporarily discontinued study drug due to an AE and did not restart. Results are expressed as proportions of participants who experience tolerability failure using the Kaplan-Meier (KM) method of estimation.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
Baseline to Week 168
Results posted on
2013-04-25
Participant Flow
Of the 112 participants randomized, 43 were in Taiwan or Singapore, 43 were in Europe (Turkey, Spain, Germany, Greece, Poland, Italy, or France), and 26 were in the US or Canada. The first participant was screened on 04 April 2006, and the last participant was randomized on 03 January 2008. Last participant observation date was 12 April 2011.
196 participants screened; 112 randomized and treated (full analysis set; randomized analysis set). Subjects without adequate decrease in HBV DNA at Week 8 could start open-label FTC/TDF. Subjects with virologic breakthrough or HBV DNA levels \> 400 copies/mL at ≥ 24 weeks could have received other therapy that may have included open-label FTC/TDF.
Participant milestones
| Measure |
Tenofovir DF
Participants in this group were randomized to receive double-blind (DB) TDF 300 mg + FTC)/TDF placebo + ETV placebo at baseline, and may have been unblinded (due to either lack of adequate decrease of HBV DNA or virologic breakthrough) and switched to open-label (OL) FTC/TDF (this study enrolled participants with decompensated liver disease, and early intervention strategies were provided if profound viral suppression was not achieved quickly).
|
FTC/TDF
Participants in this group were randomized to receive DB FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline, and may have been unblinded (due to either lack of adequate decrease of HBV DNA or virologic breakthrough) and switched to OL FTC/TDF.
|
Entecavir
Participants in this group were randomized to receive DB ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline, and may have been unblinded (due to either lack of adequate decrease of HBV DNA or virologic breakthrough) and switched to OL FTC/TDF.
|
|---|---|---|---|
|
Overall Study
STARTED
|
45
|
45
|
22
|
|
Overall Study
COMPLETED
|
28
|
37
|
16
|
|
Overall Study
NOT COMPLETED
|
17
|
8
|
6
|
Reasons for withdrawal
| Measure |
Tenofovir DF
Participants in this group were randomized to receive double-blind (DB) TDF 300 mg + FTC)/TDF placebo + ETV placebo at baseline, and may have been unblinded (due to either lack of adequate decrease of HBV DNA or virologic breakthrough) and switched to open-label (OL) FTC/TDF (this study enrolled participants with decompensated liver disease, and early intervention strategies were provided if profound viral suppression was not achieved quickly).
|
FTC/TDF
Participants in this group were randomized to receive DB FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline, and may have been unblinded (due to either lack of adequate decrease of HBV DNA or virologic breakthrough) and switched to OL FTC/TDF.
|
Entecavir
Participants in this group were randomized to receive DB ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline, and may have been unblinded (due to either lack of adequate decrease of HBV DNA or virologic breakthrough) and switched to OL FTC/TDF.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
|
Overall Study
Physician Decision
|
4
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
3
|
|
Overall Study
Adverse Event
|
5
|
2
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
3
|
0
|
Baseline Characteristics
Study Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease.
Baseline characteristics by cohort
| Measure |
Tenofovir DF
n=45 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=45 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
Entecavir
n=22 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
53 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
49 years
STANDARD_DEVIATION 10.1 • n=7 Participants
|
52 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
51 years
STANDARD_DEVIATION 10.0 • n=4 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
94 Participants
n=4 Participants
|
|
Region of Enrollment
France
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
14 participants
n=4 Participants
|
|
Region of Enrollment
Taiwan
|
13 participants
n=5 Participants
|
16 participants
n=7 Participants
|
9 participants
n=5 Participants
|
38 participants
n=4 Participants
|
|
Region of Enrollment
Greece
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
4 participants
n=5 Participants
|
7 participants
n=7 Participants
|
1 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
2 participants
n=5 Participants
|
6 participants
n=7 Participants
|
2 participants
n=5 Participants
|
10 participants
n=4 Participants
|
|
Region of Enrollment
Singapore
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
Turkey
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
2 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race
Asian
|
23 participants
n=5 Participants
|
24 participants
n=7 Participants
|
13 participants
n=5 Participants
|
60 participants
n=4 Participants
|
|
Race
Black
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race
Other
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Race
White
|
19 participants
n=5 Participants
|
20 participants
n=7 Participants
|
8 participants
n=5 Participants
|
47 participants
n=4 Participants
|
|
Ethnicity
Hispanic or Latino
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Ethnicity
Not Hispanic or Latino
|
39 participants
n=5 Participants
|
39 participants
n=7 Participants
|
21 participants
n=5 Participants
|
99 participants
n=4 Participants
|
|
Ethnicity
Not Permitted
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
1 participants
n=5 Participants
|
10 participants
n=4 Participants
|
|
Weight
|
78.1 kg
STANDARD_DEVIATION 17.02 • n=5 Participants
|
74.4 kg
STANDARD_DEVIATION 15.41 • n=7 Participants
|
77.3 kg
STANDARD_DEVIATION 16.64 • n=5 Participants
|
76.5 kg
STANDARD_DEVIATION 16.26 • n=4 Participants
|
|
Height
|
168.3 cm
STANDARD_DEVIATION 7.98 • n=5 Participants
|
168.4 cm
STANDARD_DEVIATION 8.47 • n=7 Participants
|
167.1 cm
STANDARD_DEVIATION 8.39 • n=5 Participants
|
168.1 cm
STANDARD_DEVIATION 8.20 • n=4 Participants
|
|
BMI
|
27.6 kg/m^2
STANDARD_DEVIATION 5.67 • n=5 Participants
|
26.2 kg/m^2
STANDARD_DEVIATION 5.07 • n=7 Participants
|
27.6 kg/m^2
STANDARD_DEVIATION 5.27 • n=5 Participants
|
27.0 kg/m^2
STANDARD_DEVIATION 5.35 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 168Population: Full analysis set (all randomized subjects who received at least one dose of study drug)
Tolerability failure was defined as permanent discontinuation of study drug due to a treatment-emergent adverse event (AE), including any subject who temporarily discontinued study drug due to an AE and did not restart. Results are expressed as proportions of participants who experience tolerability failure using the Kaplan-Meier (KM) method of estimation.
Outcome measures
| Measure |
Tenofovir DF
n=45 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=45 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=90 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=22 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percent Probability of Tolerability Failure
|
18 percent probability (KM estimate)
Interval 5.8 to 30.6
|
4 percent probability (KM estimate)
Interval 0.0 to 10.4
|
11 percent probability (KM estimate)
Interval 4.1 to 17.7
|
14 percent probability (KM estimate)
Interval 0.0 to 29.5
|
PRIMARY outcome
Timeframe: Baseline to Week 168Population: Full analysis set
Results are expressed as proportions of participants who experience a confirmed increase in serum creatinine of ≥ 0.5 mg/dL from baseline or a confirmed serum phosphorus level \< 2.0 mg/dL using the KM method of estimation.
Outcome measures
| Measure |
Tenofovir DF
n=45 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=45 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=90 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=22 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL
|
15 percent probability (KM estimate)
Interval 3.9 to 25.9
|
14 percent probability (KM estimate)
Interval 3.6 to 24.4
|
14 percent probability (KM estimate)
Interval 6.8 to 22.0
|
10 percent probability (KM estimate)
Interval 0.0 to 22.8
|
SECONDARY outcome
Timeframe: Baseline to 48 weeksPopulation: Participants with HBV DNA measurements at Week 48 were included in this analysis.
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 48 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Outcome measures
| Measure |
Tenofovir DF
n=36 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=38 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=18 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=92 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline
|
-2.93 log_10 copies/mL
Interval -3.84 to -2.18
|
-3.45 log_10 copies/mL
Interval -4.73 to -2.02
|
-3.61 log_10 copies/mL
Interval -4.51 to -1.31
|
-3.19 log_10 copies/mL
Interval -4.52 to -2.08
|
SECONDARY outcome
Timeframe: Baseline to 96 weeksPopulation: Full analysis set; data collected for participants who underwent liver transplant prior to Week 96 were excluded.
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 96 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Outcome measures
| Measure |
Tenofovir DF
n=34 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=35 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=16 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=85 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline
|
-3.06 log_10 copies/mL
Interval -4.17 to -2.18
|
-4.06 log_10 copies/mL
Interval -4.97 to -2.38
|
-3.32 log_10 copies/mL
Interval -4.82 to -1.26
|
-3.40 log_10 copies/mL
Interval -4.81 to -2.14
|
SECONDARY outcome
Timeframe: Baseline to 144 weeksPopulation: Full analysis set; data collected for participants who underwent liver transplant prior to Week 144 were excluded.
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 144 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Outcome measures
| Measure |
Tenofovir DF
n=28 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=34 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=15 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=77 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline
|
-3.07 log _10 copies/mL
Interval -4.36 to -2.0
|
-3.82 log _10 copies/mL
Interval -4.99 to -2.06
|
-3.76 log _10 copies/mL
Interval -5.0 to -1.33
|
-3.49 log _10 copies/mL
Interval -4.91 to -2.05
|
SECONDARY outcome
Timeframe: Baseline to 168 weeksPopulation: Full analysis set; data collected for participants who underwent liver transplant prior to Week 168 were excluded.
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 168 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Outcome measures
| Measure |
Tenofovir DF
n=26 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=31 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=15 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=72 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline
|
-3.16 log_10 copies/mL
Interval -4.57 to -1.97
|
-4.06 log_10 copies/mL
Interval -5.15 to -2.42
|
-3.77 log_10 copies/mL
Interval -5.02 to -1.33
|
-3.66 log_10 copies/mL
Interval -4.99 to -2.1
|
SECONDARY outcome
Timeframe: Week 48Population: Full analysis set; noncompleters/switch = failure analysis (participants who did not complete treatment or changed from double-blind to open-label treatment up to the time point were considered as failing to meet efficacy response criteria \[defined as not achieving viral suppression of \< 400 copies/mL\]).
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 48 was summarized.
Outcome measures
| Measure |
Tenofovir DF
n=44 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=41 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=22 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=107 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
|
70.5 percentage of participants
|
87.8 percentage of participants
|
72.7 percentage of participants
|
77.6 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Full analysis set; noncompleters/switch = failure
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 96 was summarized.
Outcome measures
| Measure |
Tenofovir DF
n=44 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=39 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=104 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96
|
59.1 percentage of participants
|
79.5 percentage of participants
|
57.1 percentage of participants
|
66.3 percentage of participants
|
SECONDARY outcome
Timeframe: Week 144Population: Full analysis set; noncompleters/switch = failure
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 144 was summarized.
Outcome measures
| Measure |
Tenofovir DF
n=44 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=40 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=105 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144
|
50.0 percentage of participants
|
77.5 percentage of participants
|
52.4 percentage of participants
|
61.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 168Population: Full analysis set; noncompleters/switch = failure
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 168 was summarized.
Outcome measures
| Measure |
Tenofovir DF
n=42 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=37 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=100 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
|
50.0 percentage of participants
|
75.7 percentage of participants
|
52.4 percentage of participants
|
60.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Biochemically evaluable analysis set (subjects in full analysis set with abnormal baseline alanine aminotransferase \[ALT\] values); noncompleters/switch = failure
Normalized ALT is defined as having a baseline ALT value \> the upper limit of the normal range (ULN), and a decrease in ALT value to ≤ ULN at the given time point.
Outcome measures
| Measure |
Tenofovir DF
n=26 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=25 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=17 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=68 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48
|
46.2 percentage of participants
|
64.0 percentage of participants
|
41.2 percentage of participants
|
51.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: Biochemically evaluable analysis set; noncompleters/switch = failure
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Outcome measures
| Measure |
Tenofovir DF
n=26 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=24 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=16 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=66 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96
|
50.0 percentage of participants
|
58.3 percentage of participants
|
31.3 percentage of participants
|
48.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 144Population: Biochemically evaluable analysis set; noncompleters/switch = failure
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Outcome measures
| Measure |
Tenofovir DF
n=26 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=25 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=16 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=67 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144
|
34.6 percentage of participants
|
64.0 percentage of participants
|
37.5 percentage of participants
|
46.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: Biochemically evaluable analysis set; noncompleters/switch = failure
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Outcome measures
| Measure |
Tenofovir DF
n=24 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=25 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=16 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=65 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168
|
29.2 percentage of participants
|
60.0 percentage of participants
|
37.5 percentage of participants
|
43.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=43 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=38 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=22 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=103 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48
|
0.0 percentage of participants
|
2.6 percentage of participants
|
0.0 percentage of participants
|
1.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: Full analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=43 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=38 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=20 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=101 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 144Population: Full analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=43 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=40 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=104 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144
|
0.0 percentage of participants
|
2.5 percentage of participants
|
0.0 percentage of participants
|
1.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: Full analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=41 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=36 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=98 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168
|
2.4 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: CPT evaluable analysis set (subjects with CPT scores ≥ 7 at baseline; because the minimum CPT score was 5, only these subjects were evaluable for analyses of ≥ 2-point decrease in CPT score); noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=27 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=25 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=12 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=64 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48
|
25.9 percentage of participants
|
48.0 percentage of participants
|
41.7 percentage of participants
|
37.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: CPT evaluable analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=26 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=25 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=10 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=61 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96
|
23.1 percentage of participants
|
52.0 percentage of participants
|
50.0 percentage of participants
|
39.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 144Population: CPT evaluable analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=27 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=27 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=11 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=65 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144
|
25.9 percentage of participants
|
51.9 percentage of participants
|
45.5 percentage of participants
|
40.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: CPT evaluable analysis set; noncompleters/switch = failure
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Outcome measures
| Measure |
Tenofovir DF
n=25 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=24 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=11 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=60 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168
|
24.0 percentage of participants
|
45.8 percentage of participants
|
45.5 percentage of participants
|
36.7 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Subjects in the full analysis set with an available score at the visit
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Outcome measures
| Measure |
Tenofovir DF
n=35 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=35 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=19 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=89 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48
|
-2.0 units on a scale
Interval -3.0 to 0.0
|
-2.0 units on a scale
Interval -4.0 to 0.0
|
-2.0 units on a scale
Interval -4.0 to -1.0
|
-2.0 units on a scale
Interval -3.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: Subjects in the full analysis set with an available score at the visit
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Outcome measures
| Measure |
Tenofovir DF
n=33 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=33 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=15 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=81 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median Change in MELD Score From Baseline at Week 96
|
-2.0 units on a scale
Interval -3.0 to 1.0
|
-3.0 units on a scale
Interval -4.0 to 0.0
|
-3.0 units on a scale
Interval -4.0 to -1.0
|
-2.0 units on a scale
Interval -4.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Week 144Population: Subjects in the full analysis set with an available score at the visit
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Outcome measures
| Measure |
Tenofovir DF
n=28 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=34 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=15 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=77 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median Change in MELD Score From Baseline at Week 144
|
-2.0 units on a scale
Interval -3.5 to -0.5
|
-1.5 units on a scale
Interval -6.0 to 0.0
|
-2.0 units on a scale
Interval -5.0 to -1.0
|
-2.0 units on a scale
Interval -4.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: Subjects in the full analysis set with an available score at the visit
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Outcome measures
| Measure |
Tenofovir DF
n=25 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=30 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=15 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=70 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Median Change in MELD Score From Baseline at Week 168
|
-2.0 units on a scale
Interval -4.0 to -1.0
|
-2.0 units on a scale
Interval -4.0 to 0.0
|
-2.0 units on a scale
Interval -5.0 to 0.0
|
-2.0 units on a scale
Interval -4.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Serologically evaluable analysis set (subjects in full analysis set with positive hepatitis B early antigen \[HBeAg\] at baseline); noncompleters/switch = failure
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=14 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=15 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=7 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=36 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Loss
|
21.4 percentage of participants
|
26.7 percentage of participants
|
0.0 percentage of participants
|
19.4 percentage of participants
|
|
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Seroconversion
|
21.4 percentage of participants
|
13.3 percentage of participants
|
0.0 percentage of participants
|
13.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: Serologically evaluable analysis set; noncompleters/switch = failure
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=14 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=15 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=6 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=35 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Loss
|
14.3 percentage of participants
|
33.3 percentage of participants
|
0.0 percentage of participants
|
20.0 percentage of participants
|
|
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Seroconversion
|
14.3 percentage of participants
|
13.3 percentage of participants
|
0.0 percentage of participants
|
11.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 144Population: Serologically evaluable analysis set; noncompleters/switch = failure
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=14 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=15 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=6 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=35 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Loss
|
14.3 percentage of participants
|
33.3 percentage of participants
|
16.7 percentage of participants
|
22.9 percentage of participants
|
|
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Seroconversion
|
14.3 percentage of participants
|
13.3 percentage of participants
|
0.0 percentage of participants
|
11.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: Serologically evaluable analysis set; noncompleters/switch = failure
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=13 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=14 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=6 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=33 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Seroconversion
|
23.1 percentage of participants
|
21.4 percentage of participants
|
0.0 percentage of participants
|
18.2 percentage of participants
|
|
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline)
HBeAg Loss
|
23.1 percentage of participants
|
35.7 percentage of participants
|
16.7 percentage of participants
|
27.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full analysis set; noncompleters/switch = failure
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=43 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=41 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=22 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=106 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48
HBsAg Loss
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48
HBsAg Seroconversion
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: Full analysis set; noncompleters/switch = failure
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=44 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=39 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=104 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96
HBsAg Seroconversion
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96
HBsAg Loss
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 144Population: Full analysis set; noncompleters/switch = failure
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=43 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=38 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=102 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144
HBsAg Seroconversion
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144
HBsAg Loss
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: Full analysis set; noncompleters/switch = failure
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Outcome measures
| Measure |
Tenofovir DF
n=41 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=36 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=21 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=98 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168
HBsAg Loss
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168
HBsAg Seroconversion
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 168Population: Liver transplantation analysis set
Outcome measures
| Measure |
Tenofovir DF
n=3 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=7 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=1 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
n=11 Participants
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results
|
NA Days
No participant in this category experienced Hepatitis B Recurrence.
|
NA Days
No participant in this category experienced Hepatitis B Recurrence.
|
NA Days
No participant in this category experienced Hepatitis B Recurrence.
|
NA Days
No participant in this category experienced Hepatitis B Recurrence.
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 168Population: Participants in the full analysis set with ADV resistance mutation at baseline were included in this analysis.
ADV resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation.
Outcome measures
| Measure |
Tenofovir DF
n=1 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=1 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
|
100 percentage of participants
|
100 percentage of participants
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 168Population: Patients in the full analysis set with LAM resistance mutation at baseline were included in this analysis.
LAM resistance mutations are defined as the presence of the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
Outcome measures
| Measure |
Tenofovir DF
n=5 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
n=8 Participants
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
n=3 Participants
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
|
100 percentage of participants
|
100 percentage of participants
|
100 percentage of participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 168Population: Participants in the full analysis set with both ADV and LAM resistance mutations at baseline were included in this analysis.
ADV resistance mutation + LAM resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation, and the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
Outcome measures
| Measure |
Tenofovir DF
n=2 Participants
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline
|
FTC/TDF
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline
|
TDF or FTC/TDF
Participants in this group include all participants who received TDF or FTC/TDF during the study.
|
Entecavir
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline
|
|---|---|---|---|---|
|
Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
|
50 percentage of participants
|
—
|
—
|
—
|
Adverse Events
Double Blind TDF
Serious events: 21 serious events
Other events: 41 other events
Deaths: 0 deaths
Double Blind FTC/TDF
Serious events: 25 serious events
Other events: 44 other events
Deaths: 0 deaths
Double Blind ETV
Serious events: 11 serious events
Other events: 20 other events
Deaths: 0 deaths
Open Label FTC/TDF
Serious events: 4 serious events
Other events: 9 other events
Deaths: 0 deaths
All TDF
Serious events: 50 serious events
Other events: 89 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Double Blind TDF
n=45 participants at risk
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo
|
Double Blind FTC/TDF
n=45 participants at risk
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo
|
Double Blind ETV
n=22 participants at risk
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo
|
Open Label FTC/TDF
n=12 participants at risk
Participants in this group were randomized to receive TDF, FTC/TDF, or ETV at the beginning of the study, but switched to open label FTC/TDF during the study.
|
All TDF
n=93 participants at risk
Participants in this group received a TDF-containing treatment (all double-blind TDF, FTC/TDF, or open-label FTC/TDF) during the study.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Ascites
|
6.7%
3/45
|
6.7%
3/45
|
4.5%
1/22
|
8.3%
1/12
|
7.5%
7/93
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
3/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
6.7%
3/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
4.4%
2/45
|
4.4%
2/45
|
4.5%
1/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Gastrointestinal disorders
Abdominal distension
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Gastric varices haemorrhage
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Haematemesis
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Inguinal hernia
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Inguinal hernia, obstructive
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Melaena
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Nausea
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Pancreatitis acute
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Gastrointestinal motility disorder
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
4.4%
2/45
|
11.1%
5/45
|
9.1%
2/22
|
0.00%
0/12
|
7.5%
7/93
|
|
Hepatobiliary disorders
Hepatorenal syndrome
|
2.2%
1/45
|
4.4%
2/45
|
0.00%
0/22
|
0.00%
0/12
|
3.2%
3/93
|
|
Hepatobiliary disorders
Chronic hepatic failure
|
2.2%
1/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
2.2%
2/93
|
|
Hepatobiliary disorders
Hepatic failure
|
2.2%
1/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
2.2%
2/93
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Hepatic lesion
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Porcelain gallbladder
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Peritonitis bacterial
|
4.4%
2/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
5.4%
5/93
|
|
Infections and infestations
Sepsis
|
2.2%
1/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/45
|
4.4%
2/45
|
0.00%
0/22
|
0.00%
0/12
|
2.2%
2/93
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Anal abscess
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Laryngitis
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Pneumococcal sepsis
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Pneumonia
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Infections and infestations
Scrotal abscess
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Subcutaneous abscess
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Infections and infestations
Cellulitis
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Infections and infestations
Hepatitis B
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Infections and infestations
Septic shock
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Infections and infestations
Wound infection
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
17.8%
8/45
|
6.7%
3/45
|
9.1%
2/22
|
8.3%
1/12
|
12.9%
12/93
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Nervous system disorders
Hepatic encephalopathy
|
6.7%
3/45
|
2.2%
1/45
|
9.1%
2/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Nervous system disorders
Encephalopathy
|
2.2%
1/45
|
4.4%
2/45
|
0.00%
0/22
|
0.00%
0/12
|
3.2%
3/93
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Nervous system disorders
Cerebrospinal fluid rhinorrhoea
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Nervous system disorders
Basal ganglia haemorrhage
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Nervous system disorders
Headache
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Injury, poisoning and procedural complications
Allergic transfusion reaction
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Device failure
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Thermal burn
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Traumatic spinal cord compression
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
General disorders
Pyrexia
|
2.2%
1/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
2.2%
2/93
|
|
General disorders
Asthenia
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
General disorders
Generalized oedema
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
General disorders
Oedema
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Renal and urinary disorders
Calculus Ureteric
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Renal and urinary disorders
Renal aneurysm
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Renal and urinary disorders
Renal failure
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Respiratory, thoracic and mediastinal disorders
Nasal disorder
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Immune system disorders
Contrast media allergy
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Immune system disorders
Liver transplant rejection
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Psychiatric disorders
Mental status change
|
4.4%
2/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
2.2%
2/93
|
|
Psychiatric disorders
Schizophreniform disorder
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Vascular disorders
Hypotension
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Vascular disorders
Aortic dissection
|
0.00%
0/45
|
0.00%
0/45
|
4.5%
1/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Investigations
Creatinine renal clearance decreased
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Metabolism and nutrition disorders
Fluid overload
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Reproductive system and breast disorders
Postmenopausal hemorrhage
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
0.00%
0/12
|
1.1%
1/93
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
2.2%
1/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
2.2%
2/93
|
Other adverse events
| Measure |
Double Blind TDF
n=45 participants at risk
Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo
|
Double Blind FTC/TDF
n=45 participants at risk
Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo
|
Double Blind ETV
n=22 participants at risk
Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo
|
Open Label FTC/TDF
n=12 participants at risk
Participants in this group were randomized to receive TDF, FTC/TDF, or ETV at the beginning of the study, but switched to open label FTC/TDF during the study.
|
All TDF
n=93 participants at risk
Participants in this group received a TDF-containing treatment (all double-blind TDF, FTC/TDF, or open-label FTC/TDF) during the study.
|
|---|---|---|---|---|---|
|
General disorders
Pyrexia
|
13.3%
6/45
|
11.1%
5/45
|
18.2%
4/22
|
0.00%
0/12
|
11.8%
11/93
|
|
General disorders
Asthenia
|
11.1%
5/45
|
4.4%
2/45
|
9.1%
2/22
|
0.00%
0/12
|
7.5%
7/93
|
|
General disorders
Fatigue
|
4.4%
2/45
|
4.4%
2/45
|
9.1%
2/22
|
0.00%
0/12
|
4.3%
4/93
|
|
General disorders
Chest pain
|
2.2%
1/45
|
0.00%
0/45
|
4.5%
1/22
|
8.3%
1/12
|
2.2%
2/93
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.9%
4/45
|
11.1%
5/45
|
9.1%
2/22
|
0.00%
0/12
|
9.7%
9/93
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
5/45
|
6.7%
3/45
|
4.5%
1/22
|
0.00%
0/12
|
8.6%
8/93
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
5/45
|
4.4%
2/45
|
0.00%
0/22
|
0.00%
0/12
|
7.5%
7/93
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
3/45
|
2.2%
1/45
|
9.1%
2/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.2%
1/45
|
6.7%
3/45
|
4.5%
1/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.2%
1/45
|
4.4%
2/45
|
4.5%
1/22
|
8.3%
1/12
|
4.3%
4/93
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Nervous system disorders
Headache
|
8.9%
4/45
|
6.7%
3/45
|
22.7%
5/22
|
8.3%
1/12
|
8.6%
8/93
|
|
Nervous system disorders
Dizziness
|
13.3%
6/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
9.7%
9/93
|
|
Nervous system disorders
Hepatic encephalopathy
|
11.1%
5/45
|
4.4%
2/45
|
13.6%
3/22
|
0.00%
0/12
|
7.5%
7/93
|
|
Gastrointestinal disorders
Abdominal pain upper
|
20.0%
9/45
|
15.6%
7/45
|
9.1%
2/22
|
16.7%
2/12
|
19.4%
18/93
|
|
Gastrointestinal disorders
Ascites
|
17.8%
8/45
|
8.9%
4/45
|
27.3%
6/22
|
8.3%
1/12
|
14.0%
13/93
|
|
Gastrointestinal disorders
Abdominal pain
|
13.3%
6/45
|
8.9%
4/45
|
13.6%
3/22
|
8.3%
1/12
|
11.8%
11/93
|
|
Gastrointestinal disorders
Nausea
|
20.0%
9/45
|
6.7%
3/45
|
4.5%
1/22
|
0.00%
0/12
|
12.9%
12/93
|
|
Gastrointestinal disorders
Abdominal distension
|
11.1%
5/45
|
8.9%
4/45
|
9.1%
2/22
|
8.3%
1/12
|
10.8%
10/93
|
|
Gastrointestinal disorders
Vomiting
|
13.3%
6/45
|
4.4%
2/45
|
9.1%
2/22
|
8.3%
1/12
|
9.7%
9/93
|
|
Gastrointestinal disorders
Dyspepsia
|
2.2%
1/45
|
13.3%
6/45
|
4.5%
1/22
|
8.3%
1/12
|
8.6%
8/93
|
|
Gastrointestinal disorders
Diarrhoea
|
8.9%
4/45
|
2.2%
1/45
|
22.7%
5/22
|
8.3%
1/12
|
5.4%
5/93
|
|
Gastrointestinal disorders
Constipation
|
6.7%
3/45
|
6.7%
3/45
|
4.5%
1/22
|
0.00%
0/12
|
6.5%
6/93
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
4.4%
2/45
|
6.7%
3/45
|
4.5%
1/22
|
0.00%
0/12
|
5.4%
5/93
|
|
Gastrointestinal disorders
Inguinal hernia
|
6.7%
3/45
|
4.4%
2/45
|
0.00%
0/22
|
0.00%
0/12
|
5.4%
5/93
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
6.7%
3/45
|
2.2%
1/45
|
4.5%
1/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/45
|
4.4%
2/45
|
9.1%
2/22
|
0.00%
0/12
|
2.2%
2/93
|
|
Gastrointestinal disorders
Gastritis
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
16.7%
2/12
|
3.2%
3/93
|
|
Gastrointestinal disorders
Haemorrhoids
|
2.2%
1/45
|
2.2%
1/45
|
0.00%
0/22
|
8.3%
1/12
|
3.2%
3/93
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Infections and infestations
Nasopharyngitis
|
11.1%
5/45
|
15.6%
7/45
|
4.5%
1/22
|
0.00%
0/12
|
12.9%
12/93
|
|
Infections and infestations
Upper respiratory tract infection
|
8.9%
4/45
|
8.9%
4/45
|
9.1%
2/22
|
16.7%
2/12
|
9.7%
9/93
|
|
Infections and infestations
Urinary tract infection
|
8.9%
4/45
|
4.4%
2/45
|
4.5%
1/22
|
8.3%
1/12
|
7.5%
7/93
|
|
Infections and infestations
Bronchitis
|
6.7%
3/45
|
2.2%
1/45
|
9.1%
2/22
|
8.3%
1/12
|
5.4%
5/93
|
|
Infections and infestations
Peritonitis bacterial
|
4.4%
2/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
5.4%
5/93
|
|
Infections and infestations
Sepsis
|
4.4%
2/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
5.4%
5/93
|
|
Infections and infestations
Influenza
|
2.2%
1/45
|
4.4%
2/45
|
0.00%
0/22
|
8.3%
1/12
|
4.3%
4/93
|
|
Infections and infestations
Rhinitis
|
0.00%
0/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
3.2%
3/93
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Infections and infestations
Wound infection
|
0.00%
0/45
|
0.00%
0/45
|
9.1%
2/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
4.4%
2/45
|
11.1%
5/45
|
9.1%
2/22
|
0.00%
0/12
|
7.5%
7/93
|
|
Hepatobiliary disorders
Cholelithiasis
|
4.4%
2/45
|
8.9%
4/45
|
0.00%
0/22
|
0.00%
0/12
|
6.5%
6/93
|
|
Hepatobiliary disorders
Jaundice
|
2.2%
1/45
|
6.7%
3/45
|
4.5%
1/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Hepatobiliary disorders
Hepatic steatosis
|
2.2%
1/45
|
2.2%
1/45
|
0.00%
0/22
|
16.7%
2/12
|
4.3%
4/93
|
|
Hepatobiliary disorders
Portal hypertension
|
4.4%
2/45
|
2.2%
1/45
|
0.00%
0/22
|
8.3%
1/12
|
4.3%
4/93
|
|
Hepatobiliary disorders
Hepatomegaly
|
4.4%
2/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
3.2%
3/93
|
|
Hepatobiliary disorders
Gallbladder polyp
|
0.00%
0/45
|
0.00%
0/45
|
9.1%
2/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
General disorders
Oedema peripheral
|
17.8%
8/45
|
6.7%
3/45
|
22.7%
5/22
|
0.00%
0/12
|
11.8%
11/93
|
|
Nervous system disorders
Encephalopathy
|
6.7%
3/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
6.5%
6/93
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
15.6%
7/45
|
13.3%
6/45
|
9.1%
2/22
|
0.00%
0/12
|
14.0%
13/93
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.9%
4/45
|
11.1%
5/45
|
4.5%
1/22
|
8.3%
1/12
|
10.8%
10/93
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Skin and subcutaneous tissue disorders
Scar pain
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
11.1%
5/45
|
4.4%
2/45
|
9.1%
2/22
|
8.3%
1/12
|
8.6%
8/93
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/45
|
8.9%
4/45
|
13.6%
3/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.7%
3/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
3.2%
3/93
|
|
Metabolism and nutrition disorders
Iron deficiency
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Psychiatric disorders
Insomnia
|
20.0%
9/45
|
8.9%
4/45
|
18.2%
4/22
|
8.3%
1/12
|
15.1%
14/93
|
|
Psychiatric disorders
Depression
|
4.4%
2/45
|
2.2%
1/45
|
4.5%
1/22
|
8.3%
1/12
|
4.3%
4/93
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
8.3%
1/12
|
2.2%
2/93
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.4%
2/45
|
8.9%
4/45
|
18.2%
4/22
|
16.7%
2/12
|
8.6%
8/93
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
2.2%
1/45
|
6.7%
3/45
|
0.00%
0/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.2%
1/45
|
2.2%
1/45
|
0.00%
0/22
|
8.3%
1/12
|
3.2%
3/93
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructrive pulmonary disease
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Respiratory, thoracic and mediastinal disorders
Nasal disorder
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Blood and lymphatic system disorders
Anaemia
|
4.4%
2/45
|
13.3%
6/45
|
9.1%
2/22
|
0.00%
0/12
|
8.6%
8/93
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.7%
3/45
|
6.7%
3/45
|
9.1%
2/22
|
0.00%
0/12
|
6.5%
6/93
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/45
|
0.00%
0/45
|
9.1%
2/22
|
0.00%
0/12
|
0.00%
0/93
|
|
Investigations
Cardiac murmur
|
4.4%
2/45
|
2.2%
1/45
|
0.00%
0/22
|
8.3%
1/12
|
4.3%
4/93
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
17.8%
8/45
|
6.7%
3/45
|
9.1%
2/22
|
8.3%
1/12
|
12.9%
12/93
|
|
Renal and urinary disorders
Renal failure
|
4.4%
2/45
|
0.00%
0/45
|
4.5%
1/22
|
8.3%
1/12
|
3.2%
3/93
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/45
|
2.2%
1/45
|
4.5%
1/22
|
8.3%
1/12
|
2.2%
2/93
|
|
Renal and urinary disorders
Calculus Ureteric
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/22
|
8.3%
1/12
|
2.2%
2/93
|
|
Renal and urinary disorders
Nephrolithiasis
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
2.2%
2/93
|
|
Renal and urinary disorders
Micturition disorder
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Vascular disorders
Hypertension
|
2.2%
1/45
|
11.1%
5/45
|
0.00%
0/22
|
8.3%
1/12
|
7.5%
7/93
|
|
Vascular disorders
Hypotension
|
8.9%
4/45
|
0.00%
0/45
|
0.00%
0/22
|
0.00%
0/12
|
4.3%
4/93
|
|
Reproductive system and breast disorders
Gynaecomastia
|
4.4%
2/45
|
6.7%
3/45
|
4.5%
1/22
|
8.3%
1/12
|
6.5%
6/93
|
|
Ear and labyrinth disorders
Vertigo
|
4.4%
2/45
|
0.00%
0/45
|
9.1%
2/22
|
8.3%
1/12
|
3.2%
3/93
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
|
Immune system disorders
Seasonal allergy
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
2.2%
2/93
|
|
Investigations
Creatinine renal clearance increased
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/22
|
8.3%
1/12
|
1.1%
1/93
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER