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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00116805
First received: June 30, 2005
Last updated: March 30, 2015
Last verified: March 2015
Results First Received: February 11, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Chronic Hepatitis B
Interventions: Drug: TDF
Drug: ADV
Drug: TDF placebo
Drug: ADV placebo
Drug: FTC/TDF

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
There were 90 enrolling sites in 15 countries. The first participant was screened on 09 June 2005, and the last participant was randomized on 15 June 2006. The last participant observation for the primary endpoint analysis (Week 48) was 11 May 2007. The last participant observation for the Week 384 analysis was 22 October 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Participant Flow for 8 periods

Period 1:   Double-blind Period Through Week 48
    TDF-TDF     ADV-TDF  
STARTED     176     90  
COMPLETED     165     85  
NOT COMPLETED     11     5  
Lost to Follow-up                 6                 2  
Protocol Violation                 1                 1  
Withdrew Consent                 4                 2  

Period 2:   Open-label Period Weeks 49 - 96
    TDF-TDF     ADV-TDF  
STARTED     154 [1]   84 [2]
COMPLETED     144     83  
NOT COMPLETED     10     1  
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 3:   Open-label Period Weeks 97 - 144
    TDF-TDF     ADV-TDF  
STARTED     144     83  
COMPLETED     133     74  
NOT COMPLETED     11     9  
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 4:   Open-label Period Weeks 145 - 192
    TDF-TDF     ADV-TDF  
STARTED     133     74  
COMPLETED     123     68  
NOT COMPLETED     10     6  
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 5:   Open-label Period Weeks 193 - 240
    TDF-TDF     ADV-TDF  
STARTED     123     68  
COMPLETED     110     64  
NOT COMPLETED     13     4  
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 6:   Open-label Period Weeks 241 - 288
    TDF-TDF     ADV-TDF  
STARTED     110     64  
COMPLETED     104     64  
NOT COMPLETED     6     0  
Safety, Tolerability, or Efficacy Reason                 2                 0  
Withdrew Consent                 4                 0  

Period 7:   Open-label Period Weeks 289 - 336
    TDF-TDF     ADV-TDF  
STARTED     104     64  
COMPLETED     98     57  
NOT COMPLETED     6     7  
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 8:   Open-label Period Weeks 337 - 384
    TDF-TDF     ADV-TDF  
STARTED     98     57  
COMPLETED     90     56  
NOT COMPLETED     8     1  
Completed Study                 1                 0  
Investigator's Discretion                 1                 0  
Lost to Follow-up                 2                 0  
Protocol Violation                 1                 0  
Withdrew Consent                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication.

Reporting Groups
  Description
TDF-TDF 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-TDF 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 Total of all reporting groups

Baseline Measures
    TDF-TDF     ADV-TDF     Total  
Number of Participants  
[units: participants]
  176     90     266  
Age  
[units: participants]
     
<=18 years     3     1     4  
Between 18 and 65 years     173     89     262  
>=65 years     0     0     0  
Age  
[units: years]
Mean (Standard Deviation)
  34  (11.3)     34  (12.2)     34  (11.6)  
Gender  
[units: participants]
     
Female     57     26     83  
Male     119     64     183  
Region of Enrollment  
[units: 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]
[units: participants]
     
Yes     169     90     259  
No     7     0     7  
Prior Lamivudine or FTC Treatment  
[units: participants]
     
Yes     8     1     9  
No     168     89     257  
Baseline Hepatitis B Deoxyribonucleic Acid (HBV DNA)  
[units: log10 copies/mL]
Mean (Standard Deviation)
  8.64  (1.076)     8.88  (0.930)     8.72  (1.033)  
Baseline Knodell Necroinflammatory Score [2]
[units: units on a scale]
Mean (Standard Deviation)
  8.3  (2.11)     8.5  (2.07)     8.4  (2.09)  
[1] 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.
[2] 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).



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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   [ Time Frame: Baseline; Week 48 ]

Measure Type Primary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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 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.

Measured Values
    TDF-TDF     ADV 10 mg  
Number of Participants Analyzed  
[units: participants]
  176     90  
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  
[units: percentage of participants]
  66.5     12.2  


Statistical Analysis 1 for 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
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Z-test
P Value [4] <0.001
Difference in proportions [5] 54.1
Standard Error of the mean (4.8)
95% Confidence Interval 44.6 to 63.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  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.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  2-sided 95% confidence interval (CI), stratified by baseline ALT was used to evaluate difference between groups in proportion of complete responders.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[5] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
Measure Description No text entered.
Time Frame Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48  
[units: percentage of participants]
  76.1     13.3  


Statistical Analysis 1 for Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] <0.001
Difference in proportions [4] 63.1
Standard Error of the mean (4.7)
95% Confidence Interval 53.8 to 72.3
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of the difference, and the CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference in zero.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Measure Description No text entered.
Time Frame Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  165     86  
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96  
[units: percentage of participants]
  77.6     77.9  


Statistical Analysis 1 for Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.801
Difference in proportions [4] -1.4
Standard Error of the mean (5.4)
95% Confidence Interval -12.0 to 9.3
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Two-sided 95% CIs, stratified by baseline ALT (baseline ALT ≤ 4 x ULN or > 4 x ULN), were used to evaluate treatment group differences.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference is zero.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384   [ Time Frame: Weeks 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
Measure Description No text entered.
Time Frame Weeks 144, 192, 240, 288, 336, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384  
[units: percentage of participants]
   
Week 144 (TDF-TDF, n = 166; ADV-TDF, n = 88)     71.7     70.5  
Week 192 (TDF-TDF, n = 165; ADV-TDF, n = 88)     67.9     71.6  
Week 240 (TDF-TDF, n = 164; ADV-TDF, n = 86)     63.4     66.3  
Week 288 (TDF-TDF, n = 163; ADV-TDF, n = 88)     61.3     64.8  
Week 336 (TDF-TDF, n = 160; ADV-TDF, n = 87)     59.4     62.1  
Week 384 (TDF-TDF, n = 155; ADV-TDF, n = 86)     56.1     60.5  

No statistical analysis provided for Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384



5.  Secondary:   Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, and 384   [ Time Frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, and 384
Measure Description No text entered.
Time Frame Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, and 384  
[units: log10 IU/mL]
Mean (Standard Deviation)
   
Week 48 (TDF-TDF, n = 160; ADV-TDF, n = 85)     -6.17  (1.067)     -3.93  (1.728)  
Week 96 (TDF-TDF, n = 144; ADV-TDF, n = 80)     -6.26  (1.137)     -6.38  (1.184)  
Week 144 (TDF-TDF, n = 131; ADV-TDF, n = 72)     -6.32  (1.098)     -6.31  (1.407)  
Week 192 (TDF-TDF, n = 117; ADV-TDF, n = 67)     -6.30  (1.203)     -6.49  (1.028)  
Week 240 (TDF-TDF, n = 105; ADV-TDF, n = 60)     -6.22  (1.217)     -6.45  (0.986)  
Week 288 (TDF-TDF, n = 101; ADV-TDF, n = 62)     -6.27  (1.248)     -6.49  (1.003)  
Week 336 (TDF-TDF, n = 94; ADV-TDF, n = 57)     -6.35  (1.208)     -6.46  (1.017)  
Week 384 (TDF-TDF, n = 83; ADV-TDF, n = 55)     -6.38  (1.167)     -6.28  (1.450)  

No statistical analysis provided for Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, and 384



6.  Secondary:   Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, and 384   [ Time Frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, and 384
Measure Description No text entered.
Time Frame Week 48; Weeks 96, 144, 192, 240, 288, 336, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, and 384  
[units: log10 IU/mL]
Mean (Standard Deviation)
   
Week 96 (TDF-TDF, n = 150; ADV-TDF, n = 81)     0.04  (0.929)     -2.42  (1.714)  
Week 144 (TDF-TDF, n = 134; ADV-TDF, n = 76)     -0.17  (0.534)     -2.27  (1.886)  
Week 192 (TDF-TDF, n = 126; ADV-TDF, n = 70)     -0.11  (0.847)     -2.36  (1.678)  
Week 240 (TDF-TDF, n = 113; ADV-TDF, n = 66)     -0.07  (0.982)     -2.55  (1.616)  
Week 288 (TDF-TDF, n = 105; ADV-TDF, n = 63)     -0.17  (0.748)     -2.62  (1.665)  
Week 336 (TDF-TDF, n = 99; ADV-TDF, n = 63)     -0.24  (0.604)     -2.69  (1.689)  
Week 384 (TDF-TDF, n = 89; ADV-TDF, n = 58)     -0.27  (0.625)     -2.41  (1.822)  

No statistical analysis provided for Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, and 384



7.  Secondary:   Percentage of Participants With Histological Response at Week 48   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With Histological Response at Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Percentage of Participants With Histological Response at Week 48  
[units: percentage of participants]
   
Yes     74.4     67.8  
No     25.6     32.2  


Statistical Analysis 1 for Percentage of Participants With Histological Response at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.320
Difference in proportions [4] 5.8
Standard Error of the mean (5.8)
95% Confidence Interval -5.6 to 17.2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).
[4] Other relevant estimation information:
  No text entered.



8.  Secondary:   Percentage of Participants With Histological Response at Week 240   [ Time Frame: Baseline; Week 240 ]

Measure Type Secondary
Measure Title Percentage of Participants With Histological Response at Week 240
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  76     48  
Percentage of Participants With Histological Response at Week 240  
[units: percentage of participants]
   
Yes     88.2     89.6  
No     11.8     10.4  

No statistical analysis provided for Percentage of Participants With Histological Response at Week 240



9.  Secondary:   Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  157     79  
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48  
[units: units on a scale]
Mean (Standard Deviation)
   
Knodell Necroinflammatory Score     -3.6  (2.30)     -3.2  (2.35)  
Ishak Necroinflammatory Score     -2.7  (1.70)     -2.6  (1.94)  

No statistical analysis provided for Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48



10.  Secondary:   Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240   [ Time Frame: Baseline; Week 240 ]

Measure Type Secondary
Measure Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  76     48  
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240  
[units: units on a scale]
Mean (Standard Deviation)
   
Knodell Necroinflammatory Score     -4.8  (2.34)     -5.1  (2.43)  
Ishak Necroinflammatory Score     -4.1  (2.14)     -4.5  (2.32)  

No statistical analysis provided for Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240



11.  Secondary:   Ranked Assessment of Necroinflammation and Fibrosis at Week 48   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Ranked Assessment of Necroinflammation and Fibrosis at Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Ranked Assessment of Necroinflammation and Fibrosis at Week 48  
[units: 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  

No statistical analysis provided for Ranked Assessment of Necroinflammation and Fibrosis at Week 48



12.  Secondary:   Ranked Assessment of Necroinflammation and Fibrosis at Week 240   [ Time Frame: Baseline; Week 240 ]

Measure Type Secondary
Measure Title Ranked Assessment of Necroinflammation and Fibrosis at Week 240
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  76     48  
Ranked Assessment of Necroinflammation and Fibrosis at Week 240  
[units: 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  

No statistical analysis provided for Ranked Assessment of Necroinflammation and Fibrosis at Week 240



13.  Secondary:   Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline and available data were analyzed; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  169     90  
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48  
[units: percentage of participants]
  68.0     54.4  


Statistical Analysis 1 for Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.032
Difference in proportions [4] 13.6
Standard Error of the mean (6.4)
95% Confidence Interval 1.1 to 26.1
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of the difference, and CI are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value corresponds to a Z-test. Statistical tests were not adjusted for baseline ALT stratum.
[4] Other relevant estimation information:
  No text entered.



14.  Secondary:   Percentage of Participants With ALT Normalization at Week 96   [ Time Frame: Baseline; Week 96 ]

Measure Type Secondary
Measure Title Percentage of Participants With ALT Normalization at Week 96
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  158     86  
Percentage of Participants With ALT Normalization at Week 96  
[units: percentage of participants]
  65.2     74.4  


Statistical Analysis 1 for Percentage of Participants With ALT Normalization at Week 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.100
Difference in proportions [4] -9.8
Standard Error of the mean (6.0)
95% Confidence Interval -21.5 to 1.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of the difference, and CI are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero.
[4] Other relevant estimation information:
  No text entered.



15.  Secondary:   Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384   [ Time Frame: Baseline; Weeks 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  169     90  
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384  
[units: percentage of participants]
   
Week 144 (TDF-TDF, n = 161; ADV-TDF, n = 87)     60.2     67.8  
Week 192 (TDF-TDF, n = 161; ADV-TDF, n = 85)     59.6     69.4  
Week 240 (TDF-TDF, n = 156; ADV-TDF, n = 85)     50.0     65.9  
Week 288 (TDF-TDF, n = 158; ADV-TDF, n = 87)     51.3     70.1  
Week 336 (TDF-TDF, n = 156; ADV-TDF, n = 84)     46.2     67.9  
Week 384 (TDF-TDF, n = 154; ADV-TDF, n = 82)     52.6     67.1  

No statistical analysis provided for Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384



16.  Secondary:   Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, and 384   [ Time Frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, and 384
Measure Description No text entered.
Time Frame Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, and 384  
[units: U/L]
Mean (Standard Deviation)
   
Week 48 (TDF-TDF, n = 160; ADV-TDF, n = 84)     -107.2  (109.44)     -106.1  (118.90)  
Week 96 (TDF-TDF, n = 141; ADV-TDF, n = 81)     -107.8  (108.07)     -120.4  (138.03)  
Week 144 (TDF-TDF, n = 131; ADV-TDF, n = 72)     -100.7  (105.96)     -126.2  (150.46)  
Week 192 (TDF-TDF, n = 119; ADV-TDF, n = 67)     -101.4  (108.63)     -139.6  (137.95)  
Week 240 (TDF-TDF, n = 102; ADV-TDF, n = 62)     -95.9  (117.03)     -134.8  (135.59)  
Week 288 (TDF-TDF, n = 100; ADV-TDF, n = 62)     -102.3  (111.68)     -130.9  (123.08)  
Week 336 (TDF-TDF, n = 95; ADV-TDF, n = 57)     -101.9  (112.72)     -132.3  (125.81)  
Week 384 (TDF-TDF, n = 85; ADV-TDF, n = 54)     -108.1  (118.05)     -133.7  (128.57)  

No statistical analysis provided for Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, and 384



17.  Secondary:   Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, and 384   [ Time Frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, and 384
Measure Description No text entered.
Time Frame Week 48; Weeks 96, 144, 192, 240, 288, 336, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, and 384  
[units: U/L]
Mean (Standard Deviation)
   
Week 96 (TDF-TDF, n = 147; ADV-TDF, n = 82)     -0.6  (23.38)     -6.0  (59.76)  
Week 144 (TDF-TDF, n = 134; ADV-TDF, n = 76)     -0.3  (21.72)     -2.7  (81.07)  
Week 192 (TDF-TDF, n = 127; ADV-TDF, n = 70)     -1.0  (19.13)     -9.2  (27.61)  
Week 240 (TDF-TDF, n = 111; ADV-TDF, n = 68)     4.2  (32.76)     -13.9  (39.51)  
Week 288 (TDF-TDF, n = 105; ADV-TDF, n = 63)     -1.8  (19.54)     -10.8  (25.29)  
Week 336 (TDF-TDF, n = 100; ADV-TDF, n = 63)     -1.2  (19.23)     -11.4  (23.36)  
Week 384 (TDF-TDF, n = 91; ADV-TDF, n = 57)     -4.2  (24.07)     -9.1  (32.28)  

No statistical analysis provided for Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, and 384



18.  Secondary:   Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  153     80  
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48  
[units: percentage of participants]
   
HBeAg Loss     22.2     17.5  
HBeAg Seroconversion     20.9     17.5  


Statistical Analysis 1 for Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.245
Difference in proportions [4] 6.1
Standard Error of the mean (5.3)
95% Confidence Interval -4.2 to 16.4
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to HBeAg loss.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.363
Difference in proportions [4] 4.7
Standard Error of the mean (5.2)
95% Confidence Interval -5.5 to 14.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to HBeAg seroconversion.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for HBeAg seroconversion corresponds to Z-test of the null hypothesis that stratum-adjusted difference is zero.
[4] Other relevant estimation information:
  No text entered.



19.  Secondary:   Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96   [ Time Frame: Baseline to Week 96 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
Measure 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 to Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  158     82  
Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96  
[units: percentage of participants]
   
HBeAg Loss     25.9     25.6  
Seroconversion to Anti-HBe     22.8     22.0  


Statistical Analysis 1 for Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.963
Difference in proportions [4] 0.3
Standard Error of the mean (5.9)
95% Confidence Interval -11.3 to 11.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to HBeAg loss.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.904
Difference in proportions [4] 0.7
Standard Error of the mean (5.6)
95% Confidence Interval -10.4 to 11.7
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to seroconversion to anti-HBe.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or >4 x ULN).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
[4] Other relevant estimation information:
  No text entered.



20.  Secondary:   Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48
Measure 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 Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Randomized and Treated Analysis Set with available data were analyzed.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  158     82  
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48  
[units: percentage of participants]
   
HBsAg Loss     3.2     0  
HBsAg Seroconversion     1.3     0  


Statistical Analysis 1 for Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.018
Difference in proportions [4] 10.9
Standard Error of the mean (4.6)
95% Confidence Interval 1.9 to 19.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to HBsAg loss.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.148
Difference in proportions [4] 4.3
Standard Error of the mean (3.0)
95% Confidence Interval -1.5 to 10.2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to HBsAg seroconversion.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).
[4] Other relevant estimation information:
  No text entered.



21.  Secondary:   Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96   [ Time Frame: Baseline; Weeks 96, 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
Measure 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 96, 144, 192, 240, 288, 336, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  171     86  
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96  
[units: percentage of participants]
   
HBsAg Loss     5.3     5.8  
Anti-HBs Seroconversion     4.1     4.7  


Statistical Analysis 1 for Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
Groups [1] All groups
Method [2] Difference in proportions
P Value [3] 0.757
Difference in proportions [4] 0.9
Standard Error of the mean (2.9)
95% Confidence Interval -4.8 to 6.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to HBsAg loss.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.733
Difference in proportions [4] 0.9
Standard Error of the mean (2.6)
95% Confidence Interval -4.2 to 5.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This information pertains to seroconversion to anti-HBs.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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).
[4] Other relevant estimation information:
  No text entered.



22.  Secondary:   Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, and 384   [ Time Frame: Baseline; Weeks 144, 192, 240, 288, 336, and 384 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, and 384
Measure 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, and 384  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, and 384  
[units: percentage of participants]
   
Loss-Wk 144 (TDF, n = 173; ADV, n = 88)     6.9     8.0  
Seroconversion-Wk 144 (TDF, n = 173; ADV, n = 88)     5.2     6.8  
Loss-Wk 192 (TDF, n = 171; ADV, n = 89)     8.2     7.9  
Seroconversion-Wk 192 (TDF, n = 171; ADV, n = 89)     5.8     6.7  
Loss-Wk 240 (TDF, n = 174; ADV, n = 88)     8.0     8.0  
Seroconversion-Wk 240 (TDF, n = 174; ADV, n = 88)     5.7     8.0  
Loss-Wk 288 (TDF, n = 172; ADV, n = 88)     7.6     8.0  
Seroconversion-Wk 288 (TDF, n = 172; ADV, n = 88)     4.7     8.0  
Loss-Wk 336 (TDF, n = 174; ADV, n = 89)     9.2     7.9  
Seroconversion-Wk 336 (TDF, n = 174; ADV, n = 89)     7.5     7.9  
Loss-Wk 384 (TDF, n = 170; ADV, n = 88)     10.0     9.1  
Seroconversion-Wk 384 (TDF, n = 170; ADV, n = 88)     7.6     8.0  

No statistical analysis provided for Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, and 384



23.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF 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.

Measured Values
    TDF-TDF     ADV-TDF  
Number of Participants Analyzed  
[units: participants]
  176     90  
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)



24.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 49 to 95 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
Measure 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 95  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  154     15     84     13  
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)



25.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 97 to 144 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  126     17     69     13  
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)



26.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 145 to 192 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  115     15     61     10  
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)



27.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 193 to 240 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  103     13     55     12  
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)



28.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 241 to 288 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  92     11     52     12  
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)



29.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 289 to 336 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  93     12     53     12  
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)



30.  Secondary:   Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)   [ Time Frame: Baseline; Weeks 337 to 384 ]

Measure Type Secondary
Measure Title Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
TDF-TDF 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-TDF With Addition of FTC 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-TDF 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-TDF With Addition of FTC 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.

Measured Values
    TDF-TDF     TDF-TDF With Addition of FTC     ADV-TDF     ADV-TDF With Addition of FTC  
Number of Participants Analyzed  
[units: participants]
  87     12     50     10  
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)  
[units: 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  

No statistical analysis provided for Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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