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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00117676
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 79 enrolling sites in 15 countries. The first participant was screened on 07 June 2005, and the last participant was randomized on 15 May 2006. The last participant observation for the primary endpoint analysis (Week 48) was 13 April 2007. The last participant observation for the Week 384 analysis was 20 September 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; as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) to their treatment 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 may have added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.

Participant Flow for 8 periods

Period 1:   Double-blind Period Through Week 48
    TDF-TDF     ADV-TDF  
STARTED     250     125  
COMPLETED     244     121  
NOT COMPLETED     6     4  
Lost to Follow-up                 1                 0  
Protocol Violation                 0                 1  
Safety, Tolerability, or Efficacy Reason                 5                 2  
Withdrew Consent                 0                 1  

Period 2:   Open-label Period: Weeks 49 - 96
    TDF-TDF     ADV-TDF  
STARTED     235 [1]   112 [1]
COMPLETED     225     110  
NOT COMPLETED     10     2  
Lost to Follow-up                 2                 0  
Safety, Tolerability, or Efficacy Reason                 3                 1  
Withdrew Consent                 5                 1  
[1] 9 participants completed 48 weeks but did not continue on study.

Period 3:   Open-label Period: Weeks 97 - 144
    TDF-TDF     ADV-TDF  
STARTED     225     110  
COMPLETED     219     109  
NOT COMPLETED     6     1  
Lost to Follow-up                 4                 1  
Safety, Tolerability, or Efficacy Reason                 1                 0  
Withdrew Consent                 1                 0  

Period 4:   Open-label Period: Weeks 145 - 192
    TDF-TDF     ADV-TDF  
STARTED     219     109  
COMPLETED     209     106  
NOT COMPLETED     10     3  
Investigator's Discretion                 2                 0  
Lost to Follow-up                 3                 1  
Withdrew Consent                 5                 2  

Period 5:   Open-label Period: Weeks 193 - 240
    TDF-TDF     ADV-TDF  
STARTED     209     106  
COMPLETED     202     103  
NOT COMPLETED     7     3  
Investigator's Discretion                 1                 1  
Lost to Follow-up                 0                 1  
Safety, Tolerability, or Efficacy Reason                 2                 0  
Withdrew Consent                 4                 1  

Period 6:   Open-label Period: Weeks 241 - 288
    TDF-TDF     ADV-TDF  
STARTED     202     103  
COMPLETED     192     100  
NOT COMPLETED     10     3  
Investigator's Discretion                 0                 1  
Lost to Follow-up                 2                 1  
Protocol Violation                 2                 0  
Safety, Tolerability, or Efficacy Reason                 1                 0  
Withdrew Consent                 5                 1  

Period 7:   Open-label Period: Weeks 289 - 336
    TDF-TDF     ADV-TDF  
STARTED     192     100  
COMPLETED     183     93  
NOT COMPLETED     9     7  
Investigator's Discretion                 7                 4  
Lost to Follow-up                 2                 2  
Withdrew Consent                 0                 1  

Period 8:   Open-label Period: Weeks 337 - 384
    TDF-TDF     ADV-TDF  
STARTED     183     93  
COMPLETED     176     90  
NOT COMPLETED     7     3  
Investigator's Discretion                 1                 1  
Lost to Follow-up                 3                 1  
Study Site Discontinued                 1                 0  
Withdrew Consent                 2                 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]
  250     125     375  
Age  
[units: participants]
     
<=18 years     0     1     1  
Between 18 and 65 years     247     123     370  
>=65 years     3     1     4  
Age  
[units: years]
Mean (Standard Deviation)
  44  (10.6)     43  (10.0)     44  (10.4)  
Gender  
[units: participants]
     
Female     57     28     85  
Male     193     97     290  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     63     30     93  
Native Hawaiian or Other Pacific Islander     7     2     9  
Black or African American     8     4     12  
White     161     81     242  
More than one race     0     0     0  
Unknown or Not Reported     11     8     19  
Region of Enrollment  
[units: participants]
     
United States     25     11     36  
Greece     19     9     28  
Spain     15     6     21  
Turkey     11     3     14  
Italy     6     0     6  
United Kingdom     5     2     7  
France     13     5     18  
Czech Republic     7     5     12  
Canada     29     18     47  
Poland     13     11     24  
Australia     14     8     22  
Bulgaria     49     23     72  
Germany     19     11     30  
Netherlands     1     1     2  
New Zealand     24     12     36  
Baseline Alanine Aminotransferase (ALT) Above the Upper Limit of the Normal (ULN) Range [1]
[units: participants]
     
Yes     236     118     354  
No     14     7     21  
Prior Lamivudine or FTC Treatment  
[units: participants]
     
Yes     43     23     66  
No     207     102     309  
Baseline Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA)  
[units: log10 copies/mL]
Mean (Standard Deviation)
  6.86  (1.308)     6.98  (1.266)     6.90  (1.294)  
Baseline Knodell Necroinflammatory Score [2]
[units: units on a scale]
Mean (Standard Deviation)
  7.8  (2.45)     7.8  (2.20)     7.8  (2.37)  
[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-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]
  250     125  
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]
   
Yes     70.8     48.8  
No     29.2     51.2  


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] 23.5
Standard Error of the mean (5.2)
95% Confidence Interval 13.2 to 33.8
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A two-sided 95% confidence interval (CI), stratified by baseline ALT (≤ 2 x ULN or > 2 x ULN) was used to evaluate the difference (tenofovir DF – adefovir dipivoxil) in the proportion of complete responders between treatment groups.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  With a sample size of 200 subjects in the tenofovir DF group and 100 subjects in the adefovir dipivoxil 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 tenofovir DF treatment was inferior to the adefovir dipivoxil treatment (difference in proportions was less than 0.100) in favor of the alternative hypothesis that the tenofovir DF treatment was not inferior.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[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 ≥ 2 x ULN or > 2 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]
  250     125  
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48  
[units: percentage of participants]
  93.2     63.2  


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] 30.3
Standard Error of the mean (4.6)
95% Confidence Interval 21.3 to 39.2
[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 is zero. Difference, standard error of the difference, and the CI are stratum adjusted based on baseline ALT category (≤ 2 x ULN or > 2 x ULN).
[4] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 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 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]
  234     122  
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96  
[units: percentage of participants]
  90.6     89.3  


Statistical Analysis 1 for Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.672
Difference in proportions [4] 1.4
Standard Error of the mean (3.4)
95% Confidence Interval -5.2 to 8.0
[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 is zero. Two-sided 95% confidence intervals, stratified by baseline ALT (baseline ALT ≤ 2 x ULN, > 2 x ULN), were used to evaluate treatment arm differences.
[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]
  250     125  
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 = 241; ADV-TDF, n = 121)     86.7     88.4  
Week 192 (TDF-TDF, n = 238; ADV-TDF, n = 121)     84.0     86.8  
Week 240 (TDF-TDF, n = 232; ADV-TDF, n = 118)     82.8     83.9  
Week 288 (TDF-TDF, n = 231; ADV-TDF, n = 117)     80.5     82.9  
Week 336 (TDF-TDF, n = 230; ADV-TDF, n = 118)     77.0     78.0  
Week 384 (TDF-TDF, n = 230; ADV-TDF, n = 118)     74.3     76.3  

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]
  250     125  
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, and 384  
[units: log10 copies/mL]
Mean (Standard Deviation)
   
Week 48 (TDF-TDF, n = 241; ADV-TDF, n = 117)     -4.57  (1.347)     -4.07  (1.331)  
Week 96 (TDF-TDF, n = 220; ADV-TDF, n = 109)     -4.54  (1.400)     -4.74  (1.260)  
Week 144 (TDF-TDF, n = 215; ADV-TDF, n = 107)     -4.61  (1.285)     -4.77  (1.285)  
Week 192 (TDF-TDF, n = 205; ADV-TDF, n = 105)     -4.56  (1.371)     -4.75  (1.271)  
Week 240 (TDF-TDF, n = 195; ADV-TDF, n = 100)     -4.59  (1.288)     -4.77  (1.303)  
Week 288 (TDF-TDF, n = 189; ADV-TDF, n = 96)     -4.61  (1.310)     -4.81  (1.310)  
Week 336 (TDF-TDF, n = 180; ADV-TDF, n = 92)     -4.61  (1.329)     -4.81  (1.307)  
Week 384 (TDF-TDF, n = 174; ADV-TDF, n = 89)     -4.56  (1.333)     -4.79  (1.314)  

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]
  250     125  
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, and 384  
[units: log10 copies/mL]
Mean (Standard Deviation)
   
Week 96 (TDF-TDF, n = 222; ADV-TDF, n = 109)     0.05  (0.536)     -0.60  (1.138)  
Week 144 (TDF-TDF, n = 215; ADV-TDF, n = 107)     -0.03  (0.378)     -0.63  (1.169)  
Week 192 (TDF-TDF, n = 206; ADV-TDF, n = 105)     0.02  (0.611)     -0.61  (1.161)  
Week 240 (TDF-TDF, n = 196; ADV-TDF, n = 100)     -0.04  (0.298)     -0.61  (1.195)  
Week 288 (TDF-TDF, n = 189; ADV-TDF, n = 97)     -0.04  (0.353)     -0.64  (1.199)  
Week 336 (TDF-TDF, n = 184; ADV-TDF, n = 94)     -0.05  (0.376)     -0.64  (1.221)  
Week 384 (TDF-TDF, n = 175; ADV-TDF, n = 90)     -0.04  (0.401)     -0.65  (1.232)  

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]
  250     125  
Percentage of Participants With Histological Response at Week 48  
[units: percentage of participants]
   
Yes     72.4     68.8  
No     27.6     31.2  


Statistical Analysis 1 for Percentage of Participants With Histological Response at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.293
Difference in proportions [4] 5.2
Standard Error of the mean (5.0)
95% Confidence Interval -4.5 to 14.9
[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:
  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 is zero. Confidence interval stratum adjusted based on baseline ALT (≤ 2 x ULN, > 2 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]
  150     74  
Percentage of Participants With Histological Response at Week 240  
[units: percentage of participants]
   
Yes     87.3     85.1  
No     12.7     14.9  

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]
  234     113  
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48  
[units: units on a scale]
Mean (Standard Deviation)
   
Knodell Necroinflammatory Score     -3.5  (2.50)     -3.4  (2.36)  
Ishak Necroinflammatory Score     -2.6  (1.93)     -2.6  (1.90)  

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]
  150     74  
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240  
[units: units on a scale]
Mean (Standard Deviation)
   
Knodell Score     -4.6  (2.50)     -4.9  (2.53)  
Ishak Score     -4.0  (2.16)     -4.2  (2.38)  

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]
  250     125  
Ranked Assessment of Necroinflammation and Fibrosis at Week 48  
[units: percentage of participants]
   
Improvement - Necroinflammation     82.0     81.6  
No Change - Necroinflammation     6.8     8.0  
Worsening - Necroinflammation     4.8     0.8  
Missing Data - Necroinflammation     6.4     9.6  
Improvement - Fibrosis     22.0     25.6  
No Change - Fibrosis     63.2     54.4  
Worsening - Fibrosis     8.4     10.4  
Missing Data - Fibrosis     6.4     9.6  

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]
  150     74  
Ranked Assessment of Necroinflammation and Fibrosis at Week 240  
[units: percentage of participants]
   
Improvement - Necroinflammation     96.7     94.6  
No Change - Necroinflammation     2.7     1.4  
Worsening - Necroinflammation     0.7     4.1  
Improvement - Fibrosis     62.0     59.5  
No Change - Fibrosis     34.0     33.8  
Worsening - Fibrosis     4.0     6.8  

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



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

Measure Type Secondary
Measure Title Percentage of Participants With 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]
  236     118  
Percentage of Participants With ALT Normalization at Week 48  
[units: percentage of participants]
  76.3     77.1  


Statistical Analysis 1 for Percentage of Participants With ALT Normalization at Week 48
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.859
Difference in proportions [4] -0.8
Standard Error of the mean (4.8)
95% Confidence Interval -10.2 to 8.5
[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:
  P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical tests were not adjusted for baseline ALT stratum. Analysis set included only randomized and treated participants with baseline ALT > ULN (biochemically evaluable analysis set).
[4] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Percentage of Participants With ALT Normalization at Weeks 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]
  221     111  
Percentage of Participants With ALT Normalization at Weeks 96  
[units: percentage of participants]
  72.4     68.5  


Statistical Analysis 1 for Percentage of Participants With ALT Normalization at Weeks 96
Groups [1] All groups
Method [2] Z-test
P Value [3] 0.359
Difference in proportions [4] 4.9
Standard Error of the mean (5.3)
95% Confidence Interval -5.5 to 15.3
[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 confidence interval are stratum adjusted (baseline ALT ≤ 2 x ULN or > 2 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]
  236     118  
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384  
[units: percentage of participants]
   
Week 144 (TDF-TDF, n = 226; ADV-TDF, n = 110)     74.3     70.0  
Week 192 (TDF-TDF, n = 223; ADV-TDF, n = 110)     68.2     76.4  
Week 240 (TDF-TDF, n = 219; ADV-TDF, n = 107)     70.3     75.7  
Week 288 (TDF-TDF, n = 216; ADV-TDF, n = 107)     69.9     72.9  
Week 336 (TDF-TDF, n = 217; ADV-TDF, n = 107)     65.9     65.4  
Week 384 (TDF-TDF, n = 216; ADV-TDF, n = 107)     65.3     69.2  

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]
  250     125  
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, and 384  
[units: units per liter]
Mean (Standard Deviation)
   
Week 48 (TDF-TDF, n = 240; ADV-TDF, n = 117)     -95.0  (102.31)     -124.4  (137.23)  
Week 96 (TDF-TDF, n = 219; ADV-TDF, n = 108)     -93.7  (106.66)     -138.5  (155.75)  
Week 144 (TDF-TDF, n = 214; ADV-TDF, n = 106)     -99.1  (105.67)     -140.0  (155.43)  
Week 192 (TDF-TDF, n = 204; ADV-TDF, n = 104)     -99.6  (109.46)     -140.3  (153.89)  
Week 240 (TDF-TDF, n = 196; ADV-TDF, n = 100)     -97.7  (104.32)     -139.5  (156.90)  
Week 288 (TDF-TDF, n = 187; ADV-TDF, n = 97)     -98.9  (104.66)     -134.7  (152.90)  
Week 336 (TDF-TDF, n = 180; ADV-TDF, n = 92)     -98.9  (106.50)     -143.1  (160.15)  
Week 384 (TDF-TDF, n = 172; ADV-TDF, n = 89)     -96.1  (105.43)     -132.6  (142.09)  

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]
  250     125  
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, and 384  
[units: units per liter]
Mean (Standard Deviation)
   
Week 96 (TDF-TDF, n = 221; ADV-TDF, n = 108)     5.0  (44.49)     -0.6  (19.87)  
Week 144 (TDF-TDF, n = 214; ADV-TDF, n = 106)     -0.6  (12.91)     -0.3  (22.48)  
Week 192 (TDF-TDF, n = 206; ADV-TDF, n = 104)     0.6  (23.01)     -3.6  (22.77)  
Week 240 (TDF-TDF, n = 197; ADV-TDF, n = 100)     -2.4  (14.61)     -3.9  (20.00)  
Week 288 (TDF-TDF, n = 187; ADV-TDF, n = 98)     -3.9  (13.35)     -4.1  (22.19)  
Week 336 (TDF-TDF, n = 184; ADV-TDF, n = 94)     -2.7  (15.61)     -1.8  (20.53)  
Week 384 (TDF-TDF, n = 173; ADV-TDF, n = 90)     -3.0  (14.15)     -3.9  (20.90)  

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 S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48   [ Time Frame: Baseline; Week 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) 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 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 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]
  250     125  
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48  
[units: percentage of participants]
   
HBsAg Loss     0     0  
Seroconversion to anti-HBs     0     0  

No statistical analysis provided for Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48



19.  Secondary:   Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96   [ Time Frame: Baseline; Week 96 ]

Measure Type Secondary
Measure Title Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96
Measure Description HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 96. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 96.
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.
Randomized and Treated Analysis Set. 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 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]
  242     121  
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96  
[units: percentage of participants]
   
HBsAg Loss     0     0  
Anti-HBs Seroconversion     0     0  

No statistical analysis provided for Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96



20.  Secondary:   Percentage of Participants With HBsAg Loss and/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 and/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 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]
  250     125  
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, and 384  
[units: percentage of participants]
   
HBsAg Loss - Week 144     0     0  
Anti-HBs Seroconversion - Week 144     0     0  
HBsAg Loss - Week 192     0     0  
Anti-HBs Seroconversion - Week 192     0     0  
HBsAg Loss - Week 240     0     0.8  
Anti-HBs Seroconversion - Week 240     0     0  
HBsAg Loss - Week 288     0     0.8  
Anti-HBs Seroconversion - Week 288     0     0.8  
HBsAg Loss - Week 336     0     0.8  
Anti-HBs Seroconversion - Week 336     0     0.8  
HBsAg Loss - Week 384     0.8     0.8  
Anti-HBs Seroconversion - Week 384     0.4     0.8  

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



21.  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 at Week 48, 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]
  250     125  
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)  
[units: participants]
   
Participants evaluated     8     42  
Changes at conserved sites in HBV polymerase     0     7  
Changes at polymorphic sites in HBV polymerase     3     14  
No genotypic changes (wild-type virus)     4     20  
Unable to be genotyped     1     1  

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



22.  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]
  235     2     112     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     6     1     0      
Changes at conserved sites within HBV polymerase     0     0     0      
Changes at polymorphic sites in HBV polymerase     2     1     0      
No genotypic changes (wild-type virus)     4     0     0      
Unable to be genotyped     0     0     0      

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



23.  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]
  220     3     110     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     4     0     0      
Changes at conserved sites within HBV polymerase     0     0     0      
Changes at polymorphic sites in HBV polymerase     1     0     0      
No genotypic changes (wild-type virus)     2     0     0      
Unable to genotype     1     0     0      

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



24.  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]
  215     3     109     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     3     1     0      
Changes at conserved sites within HBV polymerase     0     0     0      
Changes at polymorphic sites in HBV polymerase     1     0     0      
No genotypic changes (wild-type virus)     1     1     0      
Unable to genotype     1     0     0      

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



25.  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]
  204     3     105     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     1     2     2      
Changes at conserved sites within HBV polymerase     1     0     0      
Changes at polymorphic sites in HBV polymerase     0     2     0      
No genotypic changes (wild-type virus)     0     0     0      
Unable to genotype     0     0     2      

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



26.  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]
  195     3     102     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     3     1     1      
Changes at conserved sites within HBV polymerase     0     0     0      
Changes at polymorphic sites in HBV polymerase     2     1     1      
No genotypic changes (wild-type virus)     1     0     0      
Unable to genotype     0     0     0      

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



27.  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]
  189     3     97     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     0     1     1      
Changes at conserved sites within HBV polymerase     0     0     0      
Changes at polymorphic sites in HBV polymerase     0     0     0      
No genotypic changes (wild-type virus)     0     1     0      
Unable to genotype     0     0     1      

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



28.  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]
  177     3     92     0  
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)  
[units: participants]
       
Participants evaluated     1     0     0      
Changes at conserved sites within HBV polymerase     0     0     0      
Changes at polymorphic sites in HBV polymerase     0     0     0      
No genotypic changes (wild-type virus)     0     0     0      
Unable to genotype     1     0     0      

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




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  Other Adverse Events


  Limitations and Caveats
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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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