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A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B

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ClinicalTrials.gov Identifier: NCT00116805
Recruitment Status : Completed
First Posted : July 1, 2005
Results First Posted : May 19, 2010
Last Update Posted : March 9, 2017
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Hepatitis B
Interventions Drug: TDF
Drug: ADV
Drug: TDF placebo
Drug: ADV placebo
Drug: FTC/TDF
Enrollment 266

Recruitment Details Participants were enrolled at study sites in North America, Europe, and Australia/New Zealand. The first participant was screened on 09 June 2005. The last study visit occurred on 28 January 2016.
Pre-assignment Details 603 participants were screened.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description Tenofovir disoproxil fumarate (TDF) 300 mg plus placebo to match adefovir dipivoxil (ADV) (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Period Title: Double-blind Period Through Week 48
Started 176 90
Completed 165 85
Not Completed 11 5
Reason Not Completed
Lost to Follow-up             6             2
Protocol Violation             1             1
Withdrew Consent             4             2
Period Title: Open-label Period Weeks 49 - 96
Started 154 [1] 84 [2]
Completed 144 83
Not Completed 10 1
Reason Not Completed
Investigator's Discretion             1             0
Lost to Follow-up             2             0
Protocol Violation             2             0
Safety, Tolerability, or Efficacy Reason             1             0
Seroconversion             2             0
Withdrew Consent             2             1
[1]
11 participants completed 48 weeks but did not continue on study.
[2]
1 participant completed 48 weeks but did not continue on study.
Period Title: Open-label Period Weeks 97 - 144
Started 144 83
Completed 133 74
Not Completed 11 9
Reason Not Completed
Completed Study             1             0
Investigator's Discretion             2             0
Lost to Follow-up             5             2
Protocol Violation             0             1
Seroconversion             2             3
Withdrew Consent             1             3
Period Title: Open-label Period Weeks 145 - 192
Started 133 74
Completed 123 68
Not Completed 10 6
Reason Not Completed
Completed Study             1             1
Investigator's Discretion             2             0
Lost to Follow-up             3             1
Protocol Violation             1             0
Safety, Tolerability, or Efficacy Reason             0             1
Seroconversion             0             1
Withdrew Consent             3             2
Period Title: Open-label Period Weeks 193 - 240
Started 123 68
Completed 110 64
Not Completed 13 4
Reason Not Completed
Completed Study             0             1
Investigator's Discretion             1             0
Lost to Follow-up             3             0
Safety, Tolerability, or Efficacy Reason             2             2
Withdrew Consent             7             1
Period Title: Open-label Period Weeks 241 - 288
Started 110 64
Completed 104 64
Not Completed 6 0
Reason Not Completed
Safety, Tolerability, or Efficacy Reason             2             0
Withdrew Consent             4             0
Period Title: Open-label Period Weeks 289 - 336
Started 104 64
Completed 98 57
Not Completed 6 7
Reason Not Completed
Completed Study             0             1
Investigator's Discretion             3             2
Lost to Follow-up             1             1
Protocol Violation             0             1
Safety, Tolerability, or Efficacy Reason             0             1
Study Site Discontinued             0             1
Withdrew Consent             2             0
Period Title: Open-label Period Weeks 337 - 384
Started 98 57
Completed 90 56
Not Completed 8 1
Reason Not Completed
Completed Study             1             0
Investigator's Discretion             1             0
Lost to Follow-up             2             0
Protocol Violation             1             0
Withdrew Consent             3             1
Period Title: Open-label Period Weeks 385 - 432
Started 59 [1] 30 [2]
Completed 57 30
Not Completed 2 0
Reason Not Completed
Investigator’s Discretion             1             0
Withdrew Consent             1             0
[1]
31 participants completed 384 weeks but did not continue on study.
[2]
26 participants completed 384 weeks but did not continue on study.
Period Title: Open-label Period Weeks 433 - 480
Started 57 29 [1]
Completed 53 29
Not Completed 4 0
Reason Not Completed
Investigator’s Discretion             1             0
Withdrew Consent             3             0
[1]
1 participant completed 432 weeks but did not continue on study.
Arm/Group Title TDF-TDF ADV-TDF Total
Hide Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. Total of all reporting groups
Overall Number of Baseline Participants 176 90 266
Hide Baseline Analysis Population Description
Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 90 participants 266 participants
<=18 years
3
   1.7%
1
   1.1%
4
   1.5%
Between 18 and 65 years
173
  98.3%
89
  98.9%
262
  98.5%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 90 participants 266 participants
34  (11.3) 34  (12.2) 34  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 90 participants 266 participants
Female
57
  32.4%
26
  28.9%
83
  31.2%
Male
119
  67.6%
64
  71.1%
183
  68.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants 90 participants 266 participants
United States 30 14 44
Greece 1 2 3
Spain 7 2 9
Turkey 10 4 14
Italy 0 1 1
United Kingdom 6 1 7
France 11 3 14
Czech Republic 3 5 8
Canada 17 10 27
Poland 16 8 24
Australia 22 6 28
Bulgaria 17 11 28
Germany 20 8 28
Netherlands 6 4 10
New Zealand 10 11 21
Baseline Alanine Aminotransferase (ALT) above the Upper Limit of the Normal (ULN) Range   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants 90 participants 266 participants
Yes 169 90 259
No 7 0 7
[1]
Measure Description: The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Prior Lamivudine or FTC Treatment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants 90 participants 266 participants
Yes 8 1 9
No 168 89 257
Baseline Hepatitis B Deoxyribonucleic Acid (HBV DNA)  
Mean (Standard Deviation)
Unit of measure:  Log10 copies/mL
Number Analyzed 176 participants 90 participants 266 participants
8.64  (1.076) 8.88  (0.930) 8.72  (1.033)
Baseline Knodell Necroinflammatory Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 176 participants 90 participants 266 participants
8.3  (2.11) 8.5  (2.07) 8.4  (2.09)
[1]
Measure Description: Based on Knodell numerical scoring of liver biopsy specimens. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges 0 (best) to 14 (worst).
1.Primary Outcome
Title Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48
Hide Description

Complete response was a composite endpoint defined as histological response and HBV DNA < 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.

A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.

Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV 10 mg
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Unit of Measure: percentage of participants
66.5 12.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments With a sample size of 160 subjects in the TDF group and 80 subjects in the ADV group, a two group large-sample normal approximation test of proportions with a one-sided 0.025 significance level would have 95% power to reject the null hypothesis that the TDF treatment was inferior to the ADV treatment (the difference in proportions was less than -0.080) in favor of the alternative hypothesis that the TDF treatment was not inferior.
Statistical Test of Hypothesis P-Value <0.001
Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted (baseline ALT ≤ 4 x upper limit of the normal range [ULN] or > 4 x ULN) difference is 0.
Method Z-test
Comments 2-sided 95% confidence interval (CI), stratified by baseline ALT was used to evaluate difference between groups in proportion of complete responders.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 54.1
Confidence Interval (2-Sided) 95%
44.6 to 63.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.8
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Unit of Measure: percentage of participants
76.1 13.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference in zero.
Method Z-test
Comments Difference, standard error of the difference, and the CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 63.1
Confidence Interval (2-Sided) 95%
53.8 to 72.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Hide Description [Not Specified]
Time Frame Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data included for participants who discontinued study unless the discontinuation was unrelated to protocol criteria.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 165 86
Measure Type: Number
Unit of Measure: percentage of participants
77.6 77.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.801
Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference is zero.
Method Z-test
Comments Two-sided 95% CIs, stratified by baseline ALT (baseline ALT ≤ 4 x ULN or > 4 x ULN), were used to evaluate treatment group differences.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-12.0 to 9.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.4
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
Hide Description [Not Specified]
Time Frame Weeks 144, 192, 240, 288, 336, and 384
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized and Treated Analysis Set. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 166 88
Measure Type: Number
Unit of Measure: percentage of participants
Week 144 Number Analyzed 166 participants 88 participants
71.7 70.5
Week 192 Number Analyzed 165 participants 88 participants
67.9 71.6
Week 240 Number Analyzed 164 participants 86 participants
63.4 66.3
Week 288 Number Analyzed 163 participants 88 participants
61.3 64.8
Week 336 Number Analyzed 160 participants 87 participants
59.4 62.1
Week 384 Number Analyzed 155 participants 86 participants
56.1 60.5
5.Secondary Outcome
Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480
Hide Description [Not Specified]
Time Frame Weeks 432 and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added emtricitabine to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 57 29
Measure Type: Number
Unit of Measure: percentage of participants
Week 432 Number Analyzed 57 participants 28 participants
93.0 100.0
Week 480 Number Analyzed 51 participants 29 participants
98.0 96.6
6.Secondary Outcome
Title Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Hide Description [Not Specified]
Time Frame Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period..
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 160 85
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Week 48 Number Analyzed 160 participants 85 participants
-6.17  (1.067) -3.93  (1.728)
Week 96 Number Analyzed 144 participants 80 participants
-6.26  (1.137) -6.38  (1.184)
Week 144 Number Analyzed 131 participants 72 participants
-6.32  (1.098) -6.31  (1.407)
Week 192 Number Analyzed 117 participants 67 participants
-6.30  (1.203) -6.49  (1.028)
Week 240 Number Analyzed 105 participants 60 participants
-6.22  (1.217) -6.45  (0.986)
Week 288 Number Analyzed 101 participants 62 participants
-6.27  (1.248) -6.49  (1.003)
Week 336 Number Analyzed 94 participants 57 participants
-6.35  (1.208) -6.46  (1.017)
Week 384 Number Analyzed 83 participants 55 participants
-6.38  (1.167) -6.28  (1.450)
Week 432 Number Analyzed 57 participants 28 participants
-6.13  (1.306) -6.45  (1.008)
Week 480 Number Analyzed 51 participants 29 participants
-6.18  (1.300) -6.37  (1.159)
7.Secondary Outcome
Title Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Hide Description [Not Specified]
Time Frame Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 144 80
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Week 96 Number Analyzed 144 participants 80 participants
-0.10  (0.422) -2.43  (1.724)
Week 144 Number Analyzed 131 participants 72 participants
-0.19  (0.475) -2.27  (1.866)
Week 192 Number Analyzed 117 participants 67 participants
-0.20  (0.565) -2.41  (1.662)
Week 240 Number Analyzed 105 participants 60 participants
-0.14  (0.706) -2.49  (1.599)
Week 288 Number Analyzed 101 participants 62 participants
-0.18  (0.762) -2.62  (1.679)
Week 336 Number Analyzed 94 participants 57 participants
-0.25  (0.618) -2.59  (1.622)
Week 384 Number Analyzed 83 participants 55 participants
-0.29  (0.643) -2.34  (1.821)
Week 432 Number Analyzed 57 participants 28 participants
-0.13  (0.854) -2.32  (1.694)
Week 480 Number Analyzed 51 participants 29 participants
-0.24  (0.630) -2.16  (1.882)
8.Secondary Outcome
Title Percentage of Participants With Histological Response at Week 48
Hide Description Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Unit of Measure: percentage of participants
Yes 74.4 67.8
No 25.6 32.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.320
Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference in zero. Difference, standard error of the difference, and the CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 5.8
Confidence Interval (2-Sided) 95%
-5.6 to 17.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.8
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With Histological Response at Week 240
Hide Description Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Time Frame Baseline; Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 76 48
Measure Type: Number
Unit of Measure: percentage of participants
Yes 88.2 89.6
No 11.8 10.4
10.Secondary Outcome
Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
Hide Description The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with measurements at Baseline and Week 48 were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 157 79
Mean (Standard Deviation)
Unit of Measure: units on a scale
Knodell Necroinflammatory Score -3.6  (2.30) -3.2  (2.35)
Ishak Necroinflammatory Score -2.7  (1.70) -2.6  (1.94)
11.Secondary Outcome
Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
Hide Description The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Time Frame Baseline; Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 76 48
Mean (Standard Deviation)
Unit of Measure: units on a scale
Knodell Necroinflammatory Score -4.8  (2.34) -5.1  (2.43)
Ishak Necroinflammatory Score -4.1  (2.14) -4.5  (2.32)
12.Secondary Outcome
Title Ranked Assessment of Necroinflammation and Fibrosis at Week 48
Hide Description Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Unit of Measure: percentage of participants
Improvement - Necroinflammation 81.3 78.9
No Change - Necroinflammation 4.5 3.3
Worsening - Necroinflammation 3.4 5.6
Missing Data - Necroinflammation 10.8 12.2
Improvement - Fibrosis 19.9 20.0
No Change - Fibrosis 63.6 61.1
Worsening - Fibrosis 5.1 6.7
Missing Data - Fibrosis 11.4 12.2
13.Secondary Outcome
Title Ranked Assessment of Necroinflammation and Fibrosis at Week 240
Hide Description Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Time Frame Baseline; Week 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 76 48
Measure Type: Number
Unit of Measure: percentage of participants
Improvement - Necroinflammation 96.1 97.9
No Change - Necroinflammation 3.9 2.1
Worsening - Necroinflammation 0 0
Improvement - Fibrosis 56.6 58.3
No Change - Fibrosis 39.5 39.6
Worsening - Fibrosis 3.9 2.1
14.Secondary Outcome
Title Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
Hide Description ALT normalization was defined as ALT > upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline were analyzed; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 169 90
Measure Type: Number
Unit of Measure: percentage of participants
68.0 54.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments P-value corresponds to a Z-test. Statistical tests were not adjusted for baseline ALT stratum.
Method Z-test
Comments Difference, standard error of the difference, and CI are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 13.6
Confidence Interval (2-Sided) 95%
1.1 to 26.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.4
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With ALT Normalization at Week 96
Hide Description ALT normalization was defined as ALT > ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time Frame Baseline; Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 158 86
Measure Type: Number
Unit of Measure: percentage of participants
65.2 74.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.100
Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero.
Method Z-test
Comments Difference, standard error of the difference, and CI are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value -9.8
Confidence Interval (2-Sided) 95%
-21.5 to 1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.0
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
Hide Description ALT normalization was defined as ALT > ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time Frame Baseline; Weeks 144, 192, 240, 288, 336, and 384
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline and available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 161 87
Measure Type: Number
Unit of Measure: percentage of participants
Week 144 Number Analyzed 161 participants 87 participants
60.2 67.8
Week 192 Number Analyzed 161 participants 85 participants
59.6 69.4
Week 240 Number Analyzed 156 participants 85 participants
50.0 65.9
Week 288 Number Analyzed 158 participants 87 participants
51.3 70.1
Week 336 Number Analyzed 156 participants 84 participants
46.2 67.9
Week 384 Number Analyzed 154 participants 82 participants
52.6 67.1
17.Secondary Outcome
Title Percentage of Participants With ALT Normalization at Weeks 432 and 480
Hide Description ALT normalization was defined as ALT > ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time Frame Baseline; Weeks 432 and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline and with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 54 29
Measure Type: Number
Unit of Measure: percentage of participants
Week 432 Number Analyzed 54 participants 28 participants
79.6 78.6
Week 480 Number Analyzed 48 participants 29 participants
75.0 82.8
18.Secondary Outcome
Title Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Hide Description [Not Specified]
Time Frame Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 160 84
Mean (Standard Deviation)
Unit of Measure: U/L
Week 48 Number Analyzed 160 participants 84 participants
-107.2  (109.44) -106.1  (118.90)
Week 96 Number Analyzed 141 participants 81 participants
-107.8  (108.07) -120.4  (138.03)
Week 144 Number Analyzed 131 participants 72 participants
-100.7  (105.96) -126.2  (150.46)
Week 192 Number Analyzed 119 participants 67 participants
-101.4  (108.63) -139.6  (137.95)
Week 240 Number Analyzed 102 participants 62 participants
-95.9  (117.03) -134.8  (135.59)
Week 288 Number Analyzed 100 participants 62 participants
-102.3  (111.68) -130.9  (123.08)
Week 336 Number Analyzed 95 participants 57 participants
-101.9  (112.72) -132.3  (125.81)
Week 384 Number Analyzed 85 participants 54 participants
-108.1  (118.05) -133.7  (128.57)
Week 432 Number Analyzed 57 participants 28 participants
-105.0  (139.61) -162.1  (157.83)
Week 480 Number Analyzed 51 participants 29 participants
-92.3  (83.56) -157.5  (159.96)
19.Secondary Outcome
Title Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Hide Description [Not Specified]
Time Frame Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 141 81
Mean (Standard Deviation)
Unit of Measure: U/L
Week 96 Number Analyzed 141 participants 81 participants
-2.0  (17.94) -6.9  (59.64)
Week 144 Number Analyzed 131 participants 72 participants
-0.4  (21.94) -0.7  (82.70)
Week 192 Number Analyzed 119 participants 67 participants
-1.3  (19.57) -7.8  (27.07)
Week 240 Number Analyzed 102 participants 62 participants
3.7  (32.48) -8.1  (22.92)
Week 288 Number Analyzed 100 participants 62 participants
-1.6  (19.91) -10.3  (25.26)
Week 336 Number Analyzed 95 participants 57 participants
-1.2  (19.72) -9.3  (22.69)
Week 384 Number Analyzed 85 participants 54 participants
-4.4  (24.87) -6.9  (31.76)
Week 432 Number Analyzed 57 participants 28 participants
-4.3  (24.27) -11.6  (27.09)
Week 480 Number Analyzed 51 participants 29 participants
-5.5  (19.28) -7.1  (39.76)
20.Secondary Outcome
Title Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
Hide Description HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 48. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 48.
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 153 80
Measure Type: Number
Unit of Measure: percentage of participants
HBeAg Loss 22.2 17.5
HBeAg Seroconversion 20.9 17.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to HBeAg loss.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.245
Comments P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
Method Z-test
Comments Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-4.2 to 16.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to HBeAg seroconversion.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.363
Comments P-value for HBeAg seroconversion corresponds to Z-test of the null hypothesis that stratum-adjusted difference is zero.
Method Z-test
Comments Difference, standard error of difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
-5.5 to 14.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.2
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
Hide Description HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 96. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 96.
Time Frame Baseline; Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 158 82
Measure Type: Number
Unit of Measure: percentage of participants
HBeAg Loss 25.9 25.6
Seroconversion to Anti-HBe 22.8 22.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to HBeAg loss.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.963
Comments P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
Method Z-test
Comments Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-11.3 to 11.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to seroconversion to anti-HBe.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.904
Comments P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
Method Z-test
Comments Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or >4 x ULN).
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-10.4 to 11.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.6
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48
Hide Description HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48.
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with available data were analyzed.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 158 82
Measure Type: Number
Unit of Measure: percentage of participants
HBsAg Loss 3.2 0
HBsAg Seroconversion 1.3 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to HBsAg loss.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero. Difference, standard error of the difference, and confidence interval (CI) are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
1.9 to 19.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to HBsAg seroconversion.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.148
Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero. Difference, standard error of the difference, and confidence interval (CI) are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
-1.5 to 10.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.0
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
Hide Description HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
Time Frame Baseline; Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 171 86
Measure Type: Number
Unit of Measure: percentage of participants
HBsAg Loss 5.3 5.8
Anti-HBs Seroconversion 4.1 4.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to HBsAg loss.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.757
Comments P-value above for HBsAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero. Difference, standard error of the difference, and CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-4.8 to 6.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
Comments This information pertains to seroconversion to anti-HBs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.733
Comments P-value above corresponds to Z-test of the null hypothesis that stratum-adjusted difference is zero. Difference, standard error of the difference, and CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-4.2 to 5.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.6
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Hide Description HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
Time Frame Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 174 89
Measure Type: Number
Unit of Measure: percentage of participants
HBsAg Loss - Week 144 Number Analyzed 173 participants 88 participants
7.5 8.0
Anti-HBs Seroconversion - Week 144 Number Analyzed 173 participants 88 participants
5.2 6.8
HBsAg Loss - Week 192 Number Analyzed 171 participants 89 participants
9.4 7.9
Anti-HBs Seroconversion - Week 192 Number Analyzed 171 participants 89 participants
6.4 6.7
HBsAg Loss - Week 240 Number Analyzed 174 participants 88 participants
9.2 8.0
Anti-HBs Seroconversion - Week 240 Number Analyzed 174 participants 88 participants
6.3 8.0
HBsAg Loss - Week 288 Number Analyzed 173 participants 88 participants
9.2 8.0
Anti-HBs Seroconversion - Week 288 Number Analyzed 173 participants 88 participants
6.4 8.0
HBsAg Loss - Week 336 Number Analyzed 174 participants 89 participants
10.3 7.9
Anti-HBs Seroconversion - Week 336 Number Analyzed 174 participants 89 participants
7.5 7.9
HBsAg Loss - Week 384 Number Analyzed 173 participants 89 participants
11.0 9.0
Anti-HBs Seroconversion - Week 384 Number Analyzed 173 participants 89 participants
8.1 7.9
HBsAg Loss - Week 432 Number Analyzed 174 participants 88 participants
10.9 10.2
Anti-HBs Seroconversion - Week 432 Number Analyzed 172 participants 87 participants
7.6 8.0
HBsAg Loss - Week 480 Number Analyzed 174 participants 89 participants
10.9 10.1
Anti-HBs Seroconversion - Week 480 Number Analyzed 174 participants 89 participants
8.0 7.9
25.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.
Time Frame Baseline; Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF ADV-TDF
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Unit of Measure: participants
Participants evaluated 31 75
Changes at conserved sites in HBV polymerase 2 8
Changes at polymorphic sites in HBV polymerase 13 17
No genotypic changes (wild-type virus) 7 43
Unable to be genotyped 9 7
26.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 49 to 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 48 (ie, entered the open-label phase) were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 154 15 84 13
Measure Type: Number
Unit of Measure: participants
Participants evaluated 18 13 16 10
Changes at conserved sites in HBV polymerase 2 0 2 3
Changes at polymorphic sites in HBV polymerase 3 1 1 2
No genotypic changes (wild-type virus) 10 5 12 3
Unable to be genotyped 3 7 1 2
27.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 97 to 144
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 96 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 126 17 69 13
Measure Type: Number
Unit of Measure: participants
Participants evaluated 2 7 5 5
Changes at conserved sites in HBV polymerase 1 2 2 0
Changes at polymorphic sites in HBV polymerase 0 3 3 0
No genotypic changes (wild-type virus) 1 2 0 3
Unable to be genotyped 0 0 0 1
28.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 145 to 192
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 144 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 115 15 61 10
Measure Type: Number
Unit of Measure: participants
Participants evaluated 2 5 1 1
Changes at conserved sites in HBV polymerase 0 0 0 0
Changes at polymorphic sites in HBV polymerase 1 0 1 1
No genotypic changes (wild-type virus) 0 1 0 0
Unable to be genotyped 1 3 0 0
29.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 193 to 240
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 192 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 103 13 55 12
Measure Type: Number
Unit of Measure: participants
Participants evaluated 3 3 0 1
Changes at conserved sites in HBV polymerase 0 0 0 1
Changes at polymorphic sites in HBV polymerase 2 0 0 0
No genotypic changes (wild-type virus) 1 2 0 0
Unable to be genotyped 0 1 0 0
30.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 241 to 288
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 240 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 92 11 52 12
Measure Type: Number
Unit of Measure: participants
Participants evaluated 3 0 0 0
Changes at conserved sites in HBV polymerase 0 0 0 0
Changes at polymorphic sites in HBV polymerase 0 0 0 0
No genotypic changes (wild-type virus) 2 0 0 0
Unable to be genotyped 1 0 0 0
31.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 289 to 336
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 288 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 93 12 53 12
Measure Type: Number
Unit of Measure: participants
Participants evaluated 1 0 1 0
Changes at conserved sites in HBV polymerase 0 0 0 0
Changes at polymorphic sites in HBV polymerase 0 0 0 0
No genotypic changes (wild-type virus) 0 0 1 0
Unable to be genotyped 1 0 0 0
32.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 337 to 384
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 336 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 87 12 50 10
Measure Type: Number
Unit of Measure: participants
Participants evaluated 1 0 2 2
Changes at conserved sites in HBV polymerase 0 0 1 0
Changes at polymorphic sites in HBV polymerase 0 0 1 1
No genotypic changes (wild-type virus) 0 0 0 1
Unable to be genotyped 1 0 0 0
33.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 385 to 432
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 384 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 49 10 26 4
Measure Type: Number
Unit of Measure: participants
Participants evaluated 1 3 0 1
Changes at conserved sites in HBV polymerase 0 0 0 0
Changes at polymorphic sites in HBV polymerase 1 0 0 0
No genotypic changes (wild-type virus) 0 3 0 1
Unable to be genotyped 0 0 0 0
34.Secondary Outcome
Title Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)
Hide Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time Frame Baseline; Weeks 433 to 480
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Randomized and Treated Analysis Set who continued on the study after Week 432 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
Hide Arm/Group Description:
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.
ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Overall Number of Participants Analyzed 47 10 26 3
Measure Type: Number
Unit of Measure: participants
Participants evaluated 0 3 1 0
Changes at conserved sites in HBV polymerase 0 0 0 0
Changes at polymorphic sites in HBV polymerase 0 1 0 0
No genotypic changes (wild-type virus) 0 2 1 0
Unable to be genotyped 0 0 0 0
Time Frame Baseline to Week 480
Adverse Event Reporting Description Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
 
Arm/Group Title Double-Blind TDF Double-Blind ADV Open-Label TDF
Hide Arm/Group Description

Adverse events this reporting group include those occurring in the TDF-TDF group during the double-blind period only (baseline to Week 48).

TDF 300 mg plus placebo to match ADV (double-blind period).

Adverse events this reporting group include those occurring in the ADV-TDF group during the double-blind period only (baseline to Week 48).

ADV 10 mg plus placebo to match TDF (double-blind period).

Adverse events for this reporting group include those occurring during the open-label TDF 300 mg period (Week 49 up to Week 480), regardless of which group they were randomized to in the double-blind period.

TDF 300 mg + ADV placebo or ADV 10 mg + TDF placebo (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.

All-Cause Mortality
Double-Blind TDF Double-Blind ADV Open-Label TDF
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Double-Blind TDF Double-Blind ADV Open-Label TDF
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/176 (8.52%)   7/90 (7.78%)   41/238 (17.23%) 
Blood and lymphatic system disorders       
Thrombocytopenia  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Angina pectoris  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Ischaemic cardiomyopathy  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Myocarditis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Congenital, familial and genetic disorders       
Congenital anomaly in offspring  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Gastrointestinal disorders       
Inguinal hernia  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
General disorders       
Chest pain  1  0/176 (0.00%)  1/90 (1.11%)  1/238 (0.42%) 
Hepatobiliary disorders       
Cholecystitis chronic  1  0/176 (0.00%)  1/90 (1.11%)  0/238 (0.00%) 
Cholelithiasis  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Hepatitis  1  1/176 (0.57%)  0/90 (0.00%)  1/238 (0.42%) 
Infections and infestations       
Abscess soft tissue  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Diverticulitis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Epididymitis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Gastroenteritis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Groin abscess  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Hepatitis B  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Orchitis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Respiratory tract infection  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Sepsis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Skin infection  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Urinary tract infection  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Injury, poisoning and procedural complications       
Arthropod bite  1  0/176 (0.00%)  1/90 (1.11%)  0/238 (0.00%) 
Lower limb fracture  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Procedural dizziness  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Skull fracture  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Subdural haematoma  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Ulna fracture  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  6/176 (3.41%)  4/90 (4.44%)  6/238 (2.52%) 
Aspartate aminotransferase increased  1  2/176 (1.14%)  1/90 (1.11%)  2/238 (0.84%) 
Blood creatine phosphokinase increased  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Glucose urine present  1  0/176 (0.00%)  0/90 (0.00%)  2/238 (0.84%) 
Metabolism and nutrition disorders       
Diabetes mellitus inadequate control  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain  1  0/176 (0.00%)  1/90 (1.11%)  0/238 (0.00%) 
Osteoarthritis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Osteoporosis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Synovial cyst  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Colon adenoma  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Hepatic cancer  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Hepatic cancer metastatic  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Hepatic neoplasm  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Hepatocellular carcinoma  1  0/176 (0.00%)  0/90 (0.00%)  2/238 (0.84%) 
Hodgkin's disease  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Lung cancer metastatic  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Lymphoma  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Prostate cancer  1  0/176 (0.00%)  0/90 (0.00%)  2/238 (0.84%) 
Tonsillar neoplasm  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Nervous system disorders       
Diabetic neuropathy  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Facial spasm  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Seizure  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Subarachnoid haemorrhage  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Transient ischaemic attack  1  0/176 (0.00%)  0/90 (0.00%)  2/238 (0.84%) 
Psychiatric disorders       
Drug dependence  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Renal and urinary disorders       
Calculus ureteric  1  0/176 (0.00%)  0/90 (0.00%)  3/238 (1.26%) 
Tubulointerstitial nephritis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Reproductive system and breast disorders       
Ovarian cyst ruptured  1  1/176 (0.57%)  0/90 (0.00%)  0/238 (0.00%) 
Surgical and medical procedures       
Abortion induced  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Vascular disorders       
Thrombosis  1  0/176 (0.00%)  0/90 (0.00%)  1/238 (0.42%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Double-Blind TDF Double-Blind ADV Open-Label TDF
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   97/176 (55.11%)   49/90 (54.44%)   165/238 (69.33%) 
Gastrointestinal disorders       
Abdominal pain  1  6/176 (3.41%)  3/90 (3.33%)  22/238 (9.24%) 
Abdominal pain upper  1  15/176 (8.52%)  4/90 (4.44%)  25/238 (10.50%) 
Diarrhoea  1  12/176 (6.82%)  3/90 (3.33%)  12/238 (5.04%) 
Nausea  1  26/176 (14.77%)  1/90 (1.11%)  9/238 (3.78%) 
General disorders       
Fatigue  1  22/176 (12.50%)  8/90 (8.89%)  20/238 (8.40%) 
Influenza like illness  1  9/176 (5.11%)  3/90 (3.33%)  14/238 (5.88%) 
Immune system disorders       
Seasonal allergy  1  4/176 (2.27%)  1/90 (1.11%)  17/238 (7.14%) 
Infections and infestations       
Bronchitis  1  2/176 (1.14%)  4/90 (4.44%)  13/238 (5.46%) 
Influenza  1  8/176 (4.55%)  5/90 (5.56%)  25/238 (10.50%) 
Nasopharyngitis  1  22/176 (12.50%)  13/90 (14.44%)  43/238 (18.07%) 
Upper respiratory tract infection  1  7/176 (3.98%)  6/90 (6.67%)  21/238 (8.82%) 
Investigations       
Creatinine renal clearance decreased  1  1/176 (0.57%)  1/90 (1.11%)  12/238 (5.04%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  5/176 (2.84%)  6/90 (6.67%)  17/238 (7.14%) 
Back pain  1  13/176 (7.39%)  3/90 (3.33%)  18/238 (7.56%) 
Musculoskeletal pain  1  2/176 (1.14%)  3/90 (3.33%)  15/238 (6.30%) 
Myalgia  1  8/176 (4.55%)  5/90 (5.56%)  11/238 (4.62%) 
Nervous system disorders       
Dizziness  1  12/176 (6.82%)  2/90 (2.22%)  11/238 (4.62%) 
Headache  1  31/176 (17.61%)  14/90 (15.56%)  30/238 (12.61%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  10/176 (5.68%)  5/90 (5.56%)  30/238 (12.61%) 
Oropharyngeal pain  1  8/176 (4.55%)  5/90 (5.56%)  18/238 (7.56%) 
Vascular disorders       
Hypertension  1  3/176 (1.70%)  1/90 (1.11%)  24/238 (10.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institution and investigator may publish or present the results of the trial generated there with prior written consent of Gilead; or 2 years after the trial has ended at all institutions. Proposed publications/target venue must go to Gilead 30 days (manuscripts) or 15 days (abstracts/presentations) prior. Any Gilead confidential information in the document(s) must be deleted, or if requested publication delayed for up to 45 days to permit Gilead to obtain intellectual property protection.
Results Point of Contact
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
Publications of Results:
Corsa A, Liu Y, Flaherty JF, Marcellin P, Miller M, Kitrinos KM. No Detectable Resistance to Tenofovir Disoproxil Fumarate (TDF) in HBeAg+ and HBeAg- Patients With Chronic Hepatitis B (CHB) After Eight Years of Treatment [Abstract 1707]. The 65th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting (AASLD); 2014 08-10 November; Boston MA.
Marcellin P, Gane EJ, Flisiak R, Trinh HN, Petersen J, Gurel S, et al. Long Term Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B Infection is Safe and Well Tolerated and Associated with Durable Virologic Response with no Detectable Resistance: 8 Year Results from Two Phase 3 Trials [Abstract]. 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2014 November 7-11; Boston, MA.
Gane EJ, Marcellin P, Sievert W, Trinh HN, Shiffman ML, Washington MK, et al. Five years of Treatment with Tenofovir DF for Chronic Hepatitis B Infection in Asian Patients is Associated with Sustained Viral Suppression and Significant Regression of Histological Fibrosis and Cirrhosis [Poster Number 1429]. 62nd Annual Meeting of the American Association for the Study of Liver Diseases; 2011 November 4-8; San Francisco, California.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00116805     History of Changes
Other Study ID Numbers: GS-US-174-0103
2004-005120-41 ( EudraCT Number )
First Submitted: June 30, 2005
First Posted: July 1, 2005
Results First Submitted: February 11, 2010
Results First Posted: May 19, 2010
Last Update Posted: March 9, 2017