Clincosm LogoSign in Get a demo

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

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT00117676
Collaborator
(none)
382
Enrollment
80
Locations
2
Arms
131
Duration (Months)
4.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of pre-core mutant chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
382 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of Presumed Pre-Core Mutant Chronic Hepatitis B
Study Start Date :
Feb 1, 2005
Actual Primary Completion Date :
Apr 1, 2007
Actual Study Completion Date :
Jan 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: TDF-TDF

TDF plus ADV placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC tablet) to their treatment regimen in the open-label period.

Drug: TDF
300 mg tablet administered orally once daily
Other Names:
  • Viread®

    • Drug: ADV placebo
    Tablet administered orally once daily

    Drug: FTC/TDF
    200/300 mg fixed-dose combination (FDC) tablet administered orally once daily
    Other Names:
  • Truvada®

    		•
    Active Comparator: ADV-TDF

    ADV plus TDF placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF FDC tablet) to their treatment regimen in the open-label period.

    Drug: TDF
    300 mg tablet administered orally once daily
    Other Names:
  • Viread®

    • Drug: ADV
    10 mg tablet administered orally once daily
    Other Names:
  • Hepsera®

    • Drug: TDF placebo
    Tablet administered orally once daily

    Drug: FTC/TDF
    200/300 mg fixed-dose combination (FDC) tablet administered orally once daily
    Other Names:
  • Truvada®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 [Baseline; Week 48]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48 [Week 48]

    2. Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96 [Week 96]

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

    4. Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 [Weeks 432 and 480]

    5. Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 [Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480]

    6. Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 [Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480]

    7. Percentage of Participants With Histological Response at Week 48 [Baseline; Week 48]

      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.

    8. Percentage of Participants With Histological Response at Week 240 [Baseline; Week 240]

      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.

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

      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).

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

      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).

    11. Ranked Assessment of Necroinflammation and Fibrosis at Week 48 [Baseline; Week 48]

      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.

    12. Ranked Assessment of Necroinflammation and Fibrosis at Week 240 [Baseline; Week 240]

      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.

    13. Percentage of Participants With ALT Normalization at Week 48 [Baseline; Week 48]

      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.

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

      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.

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

      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.

    16. Percentage of Participants With ALT Normalization at Weeks 432 and 480 [Baseline; Weeks 432 and 480]

      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.

    17. Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 [Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480]

    18. Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 [Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480]

    19. Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 [Baseline; Week 48]

      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.

    20. Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 [Baseline; Week 96]

      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.

    21. Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 [Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480]

      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.

    22. Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) [Baseline; Week 48]

      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.

    23. Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) [Baseline; Weeks 49 to 96]

      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.

    24. Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) [Baseline; Weeks 97 to 144]

      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.

    25. Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) [Baseline; Weeks 145 to 192]

      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.

    26. Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) [Baseline; Weeks 193 to 240]

      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.

    27. Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) [Baseline; Weeks 241 to 288]

      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.

    28. Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) [Baseline; Weeks 289 to 336]

      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.

    29. Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) [Baseline; Weeks 337 to 384]

      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.

    30. Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) [Baseline; Weeks 385 to 432]

      Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

    31. Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) [Baseline; Weeks 433 to 480]

      Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 69 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for at least 6 months.

    • 18 through 69 years of age, inclusive.

    • Active hepatitis B e-antigen (HBeAg) negative chronic HBV infection, with all of the following:

    • HBeAg negative and HBeAb positive at screening

    • Alanine aminotransferase (ALT) levels > the upper limit of the normal range (ULN) and ≤ 10 x ULN

    • Serum HBV DNA > 100,000 copies/mL at screening

    • Creatinine clearance ≥ 70 mL/min

    • Hemoglobin ≥ 8 g/dL

    • Neutrophils ≥ 1,000 /mL

    • Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score < 4; however, up to 120 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment

    • Negative serum β-human chorionic gonadotropin (hCG)

    • Nucleotide naive, ie, no prior nucleotide (TDF or ADV) therapy for greater than 12 weeks

    • Nucleoside naive, ie, no prior nucleoside (any nucleoside) therapy for greater than 12 weeks. However, up to 120 patients with > 12 weeks prior lamivudine experience will be eligible

    • Willing and able to provide written informed consent

    • Had a liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline

    Key Exclusion Criteria:

    • Pregnant women, women who are breast feeding, or women who believe they may wish to become pregnant during the course of the study

    • Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study.

    • Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)

    • Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not) therapy within 6 months prior to the pre treatment biopsy

    • Evidence of hepatocellular carcinoma (HCC)

    • Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)

    • Significant renal, cardiovascular, pulmonary, or neurological disease

    • Received solid organ or bone marrow transplantation

    • Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion

    • Has proximal tubulopathy

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 La Jolla California United States 92037
    2 Pasadena California United States 91105
    3 San Diego California United States 92105
    4 San Diego California United States 92123
    5 San Francisco California United States 94115
    6 San Jose California United States 95116
    7 Atlanta Georgia United States 30308
    8 Honolulu Hawaii United States 96817
    9 Boston Massachusetts United States 02215
    10 Ann Arbor Michigan United States 48109
    11 Detroit Michigan United States 48202
    12 St. Louis Missouri United States 63104
    13 Flushing New York United States 11355
    14 New York New York United States 10003
    15 New York New York United States 10029
    16 Falls Church Virginia United States 22042
    17 Richmond Virginia United States 23298
    18 Camperdown New South Wales Australia 2050
    19 Concord New South Wales Australia 2139
    20 Westmead New South Wales Australia 2145
    21 Woolloongabba Queensland Australia 40102
    22 Clayton Victoria Australia 3168
    23 Fitzroy Victoria Australia 3065
    24 Heidelberg Victoria Australia 3084
    25 Prahan Victoria Australia 3004
    26 Sofia Bulgaria 1407
    27 Sofia Bulgaria 1431
    28 Varna Bulgaria 9010
    29 Calgary Alberta Canada T2N 4Z6
    30 Vancouver British Columbia Canada V5Z1H2
    31 Winnipeg Manitoba Canada R3E3P4
    32 Toronto Ontario Canada M5T 2S8
    33 Brno Czech Republic 62500
    34 Hradec Kralove Czech Republic
    35 Praha 4 Czech Republic 14021
    36 Praha 6 - Stresovice Czech Republic 169 02
    37 Clichy France 92110
    38 Creteil France 94010
    39 Lille France 59037
    40 Lyon France 69317
    41 Nancy France 54500
    42 Paris France 75651
    43 Strasbourg France 67901
    44 Toulouse France 31059
    45 Duesseldorf Germany 40237
    46 Frankfurt Germany 60590
    47 Hamburg Germany 20099
    48 Hannover Germany 30623
    49 Herne Germany 44623
    50 Homburg/Saar Germany 66421
    51 Mainz Germany 55131
    52 Munchen Germany 81377
    53 Tubingen Germany 72076
    54 Athens Greece 11526
    55 Larissa Greece 41110
    56 Leipzig Greece 04103
    57 Thessaloniki Greece 54636
    58 Thessaloniki Greece 56429
    59 Thessaloniki Greece 57010
    60 Bologna Italy 40138
    61 Torino Italy 10134
    62 Rotterdam Netherlands 3015
    63 Auckland New Zealand
    64 Hamilton New Zealand
    65 Whakatane New Zealand
    66 Bialystok Poland 15-540
    67 Bydgoszcz Poland 85-030
    68 Chorzow Poland 41-500
    69 Krakow Poland 31-501
    70 Warszawa Poland 01-201
    71 Wroclaw Poland 50-136
    72 Majadahonda Madrid Spain 28222
    73 Barcelona Spain 08035
    74 Valencia Spain 46009
    75 Bursa Turkey
    76 Istanbul Turkey 34098
    77 Istanbul Turkey 34899
    78 Izmir Turkey
    79 London United Kingdom NW1 2BU
    80 London United Kingdom WC1E 6HX

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT00117676
    Other Study ID Numbers:
    • GS-US-174-0102
    • 2004-005119-27
    First Posted:
    Jul 8, 2005
    Last Update Posted:
    Mar 7, 2017
    Last Verified:
    Jan 1, 2017
    Keywords provided by Gilead Sciences
    tenofovir
    adefovir
    hepatitis B virus
    HBeAg Negative
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Hepatitis, Chronic
    Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
    Adefovir dipivoxil

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in North America, Europe, and Australia/New Zealand. The first participant was screened on 07 June 2005. The last study visit occurred on 19 January 2016.
    Pre-assignment Detail 846 participants were screened.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description Tenofovir disoproxil fumarate (TDF) 300 mg plus placebo to match adefovir dipivoxil (ADV) (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC; as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) to their treatment regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.
    Period Title: Double-blind Period Through Week 48
    STARTED 254 128
    COMPLETED 244 121
    NOT COMPLETED 10 7
    Period Title: Double-blind Period Through Week 48
    STARTED 235 112
    COMPLETED 225 110
    NOT COMPLETED 10 2
    Period Title: Double-blind Period Through Week 48
    STARTED 225 110
    COMPLETED 219 109
    NOT COMPLETED 6 1
    Period Title: Double-blind Period Through Week 48
    STARTED 219 109
    COMPLETED 209 106
    NOT COMPLETED 10 3
    Period Title: Double-blind Period Through Week 48
    STARTED 209 106
    COMPLETED 202 103
    NOT COMPLETED 7 3
    Period Title: Double-blind Period Through Week 48
    STARTED 202 103
    COMPLETED 192 100
    NOT COMPLETED 10 3
    Period Title: Double-blind Period Through Week 48
    STARTED 192 100
    COMPLETED 183 93
    NOT COMPLETED 9 7
    Period Title: Double-blind Period Through Week 48
    STARTED 183 93
    COMPLETED 176 90
    NOT COMPLETED 7 3
    Period Title: Double-blind Period Through Week 48
    STARTED 82 46
    COMPLETED 82 44
    NOT COMPLETED 0 2
    Period Title: Double-blind Period Through Week 48
    STARTED 82 43
    COMPLETED 80 41
    NOT COMPLETED 2 2

    Baseline Characteristics

    Arm/Group Title TDF-TDF ADV-TDF Total
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. Total of all reporting groups
    Overall Participants 250 125 375
    Age (Count of Participants)
    <=18 years
    0
    0%
    1
    0.8%
    1
    0.3%
    Between 18 and 65 years
    247
    98.8%
    123
    98.4%
    370
    98.7%
    >=65 years
    3
    1.2%
    1
    0.8%
    4
    1.1%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    44
    (10.6)
    43
    (10.0)
    44
    (10.4)
    Gender (Count of Participants)
    Female
    57
    22.8%
    28
    22.4%
    85
    22.7%
    Male
    193
    77.2%
    97
    77.6%
    290
    77.3%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    63
    25.2%
    30
    24%
    93
    24.8%
    Native Hawaiian or Other Pacific Islander
    7
    2.8%
    2
    1.6%
    9
    2.4%
    Black or African American
    8
    3.2%
    4
    3.2%
    12
    3.2%
    White
    161
    64.4%
    81
    64.8%
    242
    64.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    11
    4.4%
    8
    6.4%
    19
    5.1%
    Region of Enrollment (participants) [Number]
    United States
    25
    10%
    11
    8.8%
    36
    9.6%
    Greece
    19
    7.6%
    9
    7.2%
    28
    7.5%
    Spain
    15
    6%
    6
    4.8%
    21
    5.6%
    Turkey
    11
    4.4%
    3
    2.4%
    14
    3.7%
    Italy
    6
    2.4%
    0
    0%
    6
    1.6%
    United Kingdom
    5
    2%
    2
    1.6%
    7
    1.9%
    France
    13
    5.2%
    5
    4%
    18
    4.8%
    Czech Republic
    7
    2.8%
    5
    4%
    12
    3.2%
    Canada
    29
    11.6%
    18
    14.4%
    47
    12.5%
    Poland
    13
    5.2%
    11
    8.8%
    24
    6.4%
    Australia
    14
    5.6%
    8
    6.4%
    22
    5.9%
    Bulgaria
    49
    19.6%
    23
    18.4%
    72
    19.2%
    Germany
    19
    7.6%
    11
    8.8%
    30
    8%
    Netherlands
    1
    0.4%
    1
    0.8%
    2
    0.5%
    New Zealand
    24
    9.6%
    12
    9.6%
    36
    9.6%
    Baseline Alanine Aminotransferase (ALT) Above the Upper Limit of the Normal (ULN) Range (participants) [Number]
    Yes
    236
    94.4%
    118
    94.4%
    354
    94.4%
    No
    14
    5.6%
    7
    5.6%
    21
    5.6%
    Prior Lamivudine or FTC Treatment (participants) [Number]
    Yes
    43
    17.2%
    23
    18.4%
    66
    17.6%
    No
    207
    82.8%
    102
    81.6%
    309
    82.4%
    Baseline Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    6.86
    (1.308)
    6.98
    (1.266)
    6.90
    (1.294)
    Baseline Knodell Necroinflammatory Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    7.8
    (2.45)
    7.8
    (2.20)
    7.8
    (2.37)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 125
    Yes
    70.8
    28.3%
    48.8
    39%
    No
    29.2
    11.7%
    51.2
    41%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
    Comments 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.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments 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.
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted (baseline ALT ≥ 2 x ULN or > 2 x ULN) difference is 0.
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 23.5
    Confidence Interval (2-Sided) 95%
    13.2 to 33.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.2
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
    Description
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 125
    Number [percentage of participants]
    93.2
    37.3%
    63.2
    50.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference 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).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 30.3
    Confidence Interval (2-Sided) 95%
    21.3 to 39.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.6
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96
    Description
    Time Frame Week 96

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 234 122
    Number [percentage of participants]
    90.6
    36.2%
    89.3
    71.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.672
    Comments 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.
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -5.2 to 8.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.4
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
    Description
    Time Frame Weeks 144, 192, 240, 288, 336, and 384

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 241 121
    Week 144
    86.7
    34.7%
    88.4
    70.7%
    Week 192
    84.0
    33.6%
    86.8
    69.4%
    Week 240
    82.8
    33.1%
    83.9
    67.1%
    Week 288
    80.5
    32.2%
    82.9
    66.3%
    Week 336
    77.0
    30.8%
    78.0
    62.4%
    Week 384
    74.3
    29.7%
    76.3
    61%
    5. Secondary Outcome
    Title Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480
    Description
    Time Frame Weeks 432 and 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added emtricitabine to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 82 44
    Week 432
    97.6
    39%
    97.7
    78.2%
    Week 480
    100.0
    40%
    100.0
    80%
    6. Secondary Outcome
    Title Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
    Description
    Time Frame Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 241 117
    Week 48
    -4.57
    (1.347)
    -4.07
    (1.331)
    Week 96
    -4.54
    (1.400)
    -4.74
    (1.260)
    Week 144
    -4.61
    (1.285)
    -4.77
    (1.285)
    Week 192
    -4.56
    (1.371)
    -4.75
    (1.271)
    Week 240
    -4.59
    (1.288)
    -4.77
    (1.303)
    Week 288
    -4.61
    (1.310)
    -4.81
    (1.310)
    Week 336
    -4.61
    (1.329)
    -4.81
    (1.307)
    Week 384
    -4.56
    (1.333)
    -4.79
    (1.314)
    Week 432
    -4.60
    (1.376)
    -4.69
    (1.370)
    Week 480
    -4.57
    (1.329)
    -4.75
    (1.349)
    7. Secondary Outcome
    Title Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
    Description
    Time Frame Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 220 109
    Week 96
    0.02
    (0.424)
    -0.60
    (1.138)
    Week 144
    -0.03
    (0.378)
    -0.63
    (1.169)
    Week 192
    0.01
    (0.610)
    -0.61
    (1.161)
    Week 240
    -0.04
    (0.299)
    -0.61
    (1.195)
    Week 288
    -0.04
    (0.353)
    -0.64
    (1.203)
    Week 336
    -0.05
    (0.380)
    -0.65
    (1.230)
    Week 384
    -0.02
    (0.241)
    -0.66
    (1.237)
    Week 432
    -0.04
    (0.393)
    -0.67
    (1.378)
    Week 480
    -0.05
    (0.366)
    -0.72
    (1.283)
    8. Secondary Outcome
    Title Percentage of Participants With Histological Response at Week 48
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 125
    Yes
    72.4
    29%
    68.8
    55%
    No
    27.6
    11%
    31.2
    25%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.293
    Comments 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).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 5.2
    Confidence Interval (2-Sided) 95%
    -4.5 to 14.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.0
    Estimation Comments
    9. Secondary Outcome
    Title Percentage of Participants With Histological Response at Week 240
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 150 74
    Yes
    87.3
    34.9%
    85.1
    68.1%
    No
    12.7
    5.1%
    14.9
    11.9%
    10. Secondary Outcome
    Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with measurements at Baseline and Week 48 were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 234 113
    Knodell Necroinflammatory Score
    -3.5
    (2.50)
    -3.4
    (2.36)
    Ishak Necroinflammatory Score
    -2.6
    (1.93)
    -2.6
    (1.90)
    11. Secondary Outcome
    Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 150 74
    Knodell Score
    -4.6
    (2.50)
    -4.9
    (2.53)
    Ishak Score
    -4.0
    (2.16)
    -4.2
    (2.38)
    12. Secondary Outcome
    Title Ranked Assessment of Necroinflammation and Fibrosis at Week 48
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 125
    Improvement - Necroinflammation
    82.0
    32.8%
    81.6
    65.3%
    No Change - Necroinflammation
    6.8
    2.7%
    8.0
    6.4%
    Worsening - Necroinflammation
    4.8
    1.9%
    0.8
    0.6%
    Missing Data - Necroinflammation
    6.4
    2.6%
    9.6
    7.7%
    Improvement - Fibrosis
    22.0
    8.8%
    25.6
    20.5%
    No Change - Fibrosis
    63.2
    25.3%
    54.4
    43.5%
    Worsening - Fibrosis
    8.4
    3.4%
    10.4
    8.3%
    Missing Data - Fibrosis
    6.4
    2.6%
    9.6
    7.7%
    13. Secondary Outcome
    Title Ranked Assessment of Necroinflammation and Fibrosis at Week 240
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 150 74
    Improvement - Necroinflammation
    96.7
    38.7%
    94.6
    75.7%
    No Change - Necroinflammation
    2.7
    1.1%
    1.4
    1.1%
    Worsening - Necroinflammation
    0.7
    0.3%
    4.1
    3.3%
    Improvement - Fibrosis
    62.0
    24.8%
    59.5
    47.6%
    No Change - Fibrosis
    34.0
    13.6%
    33.8
    27%
    Worsening - Fibrosis
    4.0
    1.6%
    6.8
    5.4%
    14. Secondary Outcome
    Title Percentage of Participants With ALT Normalization at Week 48
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline were analyzed; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 236 118
    Number [percentage of participants]
    76.3
    30.5%
    77.1
    61.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.859
    Comments 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).
    Method Z-test
    Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero.
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -10.2 to 8.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.8
    Estimation Comments
    15. Secondary Outcome
    Title Percentage of Participants With ALT Normalization at Weeks 96
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 221 111
    Number [percentage of participants]
    72.4
    29%
    68.5
    54.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV-TDF
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.359
    Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero.
    Method Z-test
    Comments Difference, standard error of the difference, and confidence interval are stratum adjusted (baseline ALT ≤ 2 x ULN or > 2 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 4.9
    Confidence Interval (2-Sided) 95%
    -5.5 to 15.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.3
    Estimation Comments
    16. Secondary Outcome
    Title Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline and available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 226 110
    Week 144
    74.3
    29.7%
    70.0
    56%
    Week 192
    68.2
    27.3%
    76.4
    61.1%
    Week 240
    70.3
    28.1%
    75.7
    60.6%
    Week 288
    69.9
    28%
    72.9
    58.3%
    Week 336
    65.9
    26.4%
    65.4
    52.3%
    Week 384
    65.3
    26.1%
    69.2
    55.4%
    17. Secondary Outcome
    Title Percentage of Participants With ALT Normalization at Weeks 432 and 480
    Description ALT normalization was defined as ALT > ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
    Time Frame Baseline; Weeks 432 and 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with ALT > ULN at baseline and with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 74 39
    Week 432
    86.5
    34.6%
    87.2
    69.8%
    Week 480
    80.0
    32%
    88.9
    71.1%
    18. Secondary Outcome
    Title Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
    Description
    Time Frame Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 240 117
    Week 48
    -95.0
    (102.31)
    -124.4
    (137.23)
    Week 96
    -93.7
    (106.66)
    -138.5
    (155.75)
    Week 144
    -99.1
    (105.67)
    -140.0
    (155.43)
    Week 192
    -99.6
    (109.46)
    -140.3
    (153.89)
    Week 240
    -97.7
    (104.32)
    -139.5
    (156.90)
    Week 288
    -98.9
    (104.66)
    -134.7
    (152.90)
    Week 336
    -98.9
    (106.50)
    -143.1
    (160.15)
    Week 384
    -96.1
    (105.43)
    -132.6
    (142.09)
    Week 432
    -97.0
    (115.09)
    -131.9
    (136.65)
    Week 480
    -94.9
    (117.60)
    -129.2
    (139.24)
    19. Secondary Outcome
    Title Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
    Description
    Time Frame Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 219 108
    Week 96
    2.4
    (22.01)
    -0.6
    (19.87)
    Week 144
    -0.6
    (12.91)
    -0.3
    (22.48)
    Week 192
    0.7
    (23.07)
    -3.6
    (22.77)
    Week 240
    -2.5
    (14.64)
    -3.9
    (20.00)
    Week 288
    -3.9
    (13.35)
    -4.1
    (22.30)
    Week 336
    -2.6
    (15.69)
    -2.0
    (20.61)
    Week 384
    -2.9
    (14.13)
    -3.9
    (21.00)
    Week 432
    -4.6
    (15.65)
    -8.9
    (29.12)
    Week 480
    -2.8
    (15.92)
    -5.9
    (24.12)
    20. Secondary Outcome
    Title Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set were analyzed. The missing = failure approach was used.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 125
    HBsAg Loss
    0
    0%
    0
    0%
    Seroconversion to anti-HBs
    0
    0%
    0
    0%
    21. Secondary Outcome
    Title Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 242 121
    HBsAg Loss
    0
    0%
    0
    0%
    Anti-HBs Seroconversion
    0
    0%
    0
    0%
    22. Secondary Outcome
    Title Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480
    Description HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
    Time Frame Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480

    Outcome Measure Data

    Analysis Population Description
    Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 123
    HBsAg Loss - Week 144
    0
    0%
    0
    0%
    Anti-HBs Seroconversion - Week 144
    0
    0%
    0
    0%
    HBsAg Loss - Week 192
    0
    0%
    0
    0%
    Anti-HBs Seroconversion - Week 192
    0
    0%
    0
    0%
    HBsAg Loss - Week 240
    0
    0%
    0.8
    0.6%
    Anti-HBs Seroconversion - Week 240
    0
    0%
    0
    0%
    HBsAg Loss - Week 288
    0
    0%
    0.8
    0.6%
    Anti-HBs Seroconversion - Week 288
    0
    0%
    0.8
    0.6%
    HBsAg Loss - Week 336
    0
    0%
    0.8
    0.6%
    Anti-HBs Seroconversion - Week 336
    0
    0%
    0.8
    0.6%
    HBsAg Loss - Week 384
    0.8
    0.3%
    0.8
    0.6%
    Anti-HBs Seroconversion - Week 384
    0.4
    0.2%
    0.8
    0.6%
    HBsAg Loss - Week 432
    1.2
    0.5%
    1.6
    1.3%
    Anti-HBs Seroconversion - Week 432
    0.4
    0.2%
    0.8
    0.6%
    HBsAg Loss - Week 480
    1.2
    0.5%
    2.4
    1.9%
    Anti-HBs Seroconversion - Week 480
    0.8
    0.3%
    0.8
    0.6%
    23. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 250 125
    Participants evaluated
    8
    3.2%
    42
    33.6%
    Changes at conserved sites in HBV polymerase
    0
    0%
    7
    5.6%
    Changes at polymorphic sites in HBV polymerase
    3
    1.2%
    14
    11.2%
    No genotypic changes (wild-type virus)
    4
    1.6%
    20
    16%
    Unable to be genotyped
    1
    0.4%
    1
    0.8%
    24. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
    Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition.
    Time Frame Baseline; Weeks 49 to 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 48 (ie, entered the open-label phase) were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 235 2 112 0
    Participants evaluated
    6
    2.4%
    1
    0.8%
    0
    0%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    2
    0.8%
    1
    0.8%
    0
    0%
    No genotypic changes (wild-type virus)
    4
    1.6%
    0
    0%
    0
    0%
    Unable to be genotyped
    0
    0%
    0
    0%
    0
    0%
    25. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 96 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 220 3 110 0
    Participants evaluated
    4
    1.6%
    0
    0%
    0
    0%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    1
    0.4%
    0
    0%
    0
    0%
    No genotypic changes (wild-type virus)
    2
    0.8%
    0
    0%
    0
    0%
    Unable to genotype
    1
    0.4%
    0
    0%
    0
    0%
    26. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 144 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 215 3 109 0
    Participants evaluated
    3
    1.2%
    1
    0.8%
    0
    0%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    1
    0.4%
    0
    0%
    0
    0%
    No genotypic changes (wild-type virus)
    1
    0.4%
    1
    0.8%
    0
    0%
    Unable to genotype
    1
    0.4%
    0
    0%
    0
    0%
    27. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 192 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 204 3 105 0
    Participants evaluated
    1
    0.4%
    2
    1.6%
    2
    0.5%
    Changes at conserved sites within HBV polymerase
    1
    0.4%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    2
    1.6%
    0
    0%
    No genotypic changes (wild-type virus)
    0
    0%
    0
    0%
    0
    0%
    Unable to genotype
    0
    0%
    0
    0%
    2
    0.5%
    28. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 240 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 195 3 102 0
    Participants evaluated
    3
    1.2%
    1
    0.8%
    1
    0.3%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    2
    0.8%
    1
    0.8%
    1
    0.3%
    No genotypic changes (wild-type virus)
    1
    0.4%
    0
    0%
    0
    0%
    Unable to genotype
    0
    0%
    0
    0%
    0
    0%
    29. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 288 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 189 3 97 0
    Participants evaluated
    0
    0%
    1
    0.8%
    1
    0.3%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    No genotypic changes (wild-type virus)
    0
    0%
    1
    0.8%
    0
    0%
    Unable to genotype
    0
    0%
    0
    0%
    1
    0.3%
    30. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
    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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 336 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 177 3 92 0
    Participants evaluated
    1
    0.4%
    0
    0%
    0
    0%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    No genotypic changes (wild-type virus)
    0
    0%
    0
    0%
    0
    0%
    Unable to genotype
    1
    0.4%
    0
    0%
    0
    0%
    31. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)
    Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
    Time Frame Baseline; Weeks 385 to 432

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 384 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 81 1 46 0
    Participants evaluated
    2
    0.8%
    0
    0%
    1
    0.3%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    1
    0.3%
    No genotypic changes (wild-type virus)
    2
    0.8%
    0
    0%
    0
    0%
    Unable to genotype
    0
    0%
    0
    0%
    0
    0%
    32. Secondary Outcome
    Title Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)
    Description Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
    Time Frame Baseline; Weeks 433 to 480

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who continued on the study after Week 432 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
    Arm/Group Title TDF-TDF TDF-TDF With Addition of FTC ADV-TDF ADV-TDF With Addition of FTC
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
    Measure Participants 81 1 43 0
    Participants evaluated
    0
    0%
    0
    0%
    0
    0%
    Changes at conserved sites within HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    No genotypic changes (wild-type virus)
    0
    0%
    0
    0%
    0
    0%
    Unable to genotype
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Baseline to Week 480
    Adverse Event Reporting Description Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
    Arm/Group Title Double-Blind TDF Double-Blind ADV Open-Label TDF
    Arm/Group Description Adverse events this reporting group include those occurring in the TDF-TDF group during the double-blind period only (baseline to Week 48). TDF 300 mg plus placebo to match ADV (double-blind period). Adverse events this reporting group include those occurring in the ADV-TDF group during the double-blind period only (baseline to Week 48). ADV 10 mg plus placebo to match TDF (double-blind period). Adverse events for this reporting group include those occurring during the open-label TDF 300 mg period (Week 49 up to Week 384), regardless of which group they were randomized to in the double-blind period. TDF 300 mg+ADV placebo or ADV 10 mg+TDF placebo (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.
    All Cause Mortality
    Double-Blind TDF Double-Blind ADV Open-Label TDF
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Double-Blind TDF Double-Blind ADV Open-Label TDF
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/250 (4.8%) 7/125 (5.6%) 90/347 (25.9%)
    Blood and lymphatic system disorders
    Anaemia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Iron deficiency anaemia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lymphadenopathy 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Cardiac disorders
    Angina pectoris 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Angina unstable 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Atrial fibrillation 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Coronary artery disease 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Myocardial infarction 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Myocardial ischaemia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Sinus bradycardia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Sinus node dysfunction 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Endocrine disorders
    Hyperparathyroidism 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Eye disorders
    Lens disorder 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Gastrointestinal disorders
    Abdominal hernia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Abdominal pain 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Abdominal pain upper 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Colitis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Diarrhoea 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Gastrooesophageal reflux disease 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Haemorrhoidal haemorrhage 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Haemorrhoids 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Inguinal hernia 1/250 (0.4%) 0/125 (0%) 1/347 (0.3%)
    Intestinal obstruction 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Pancreatitis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Pancreatitis acute 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Small intestinal obstruction 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Umbilical hernia 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    General disorders
    Chest pain 0/250 (0%) 0/125 (0%) 4/347 (1.2%)
    Condition aggravated 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Granuloma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Malaise 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Hepatobiliary disorders
    Cholecystitis acute 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Cholelithiasis 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Hepatic cirrhosis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Hepatitis 0/250 (0%) 1/125 (0.8%) 1/347 (0.3%)
    Liver disorder 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Infections and infestations
    Abscess limb 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Appendicitis 0/250 (0%) 0/125 (0%) 3/347 (0.9%)
    Cellulitis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Diverticulitis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Erysipelas 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Liver abscess 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lower respiratory tract infection 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lung infection 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Pneumonia 0/250 (0%) 0/125 (0%) 5/347 (1.4%)
    Pneumonia pneumococcal 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Sepsis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Septic shock 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Urinary tract infection 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Wound infection 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Injury, poisoning and procedural complications
    Arterial injury 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Concussion 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Fall 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Foot fracture 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Hand fracture 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Head injury 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Injury 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Limb injury 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lower limb fracture 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Meniscus injury 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Overdose 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Post procedural haemorrhage 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Procedural hypotension 0/250 (0%) 1/125 (0.8%) 0/347 (0%)
    Road traffic accident 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Tibia fracture 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Wound 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Wrist fracture 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Investigations
    Alanine aminotransferase increased 3/250 (1.2%) 0/125 (0%) 2/347 (0.6%)
    Aspartate aminotransferase increased 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Blood creatine phosphokinase increased 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Hepatitis B DNA increased 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Metabolism and nutrition disorders
    Diabetes mellitus 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Diabetes mellitus inadequate control 0/250 (0%) 1/125 (0.8%) 0/347 (0%)
    Diabetic ketoacidosis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Bone cyst 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Bursitis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Intervertebral disc protrusion 0/250 (0%) 0/125 (0%) 3/347 (0.9%)
    Musculoskeletal pain 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Myopathy toxic 0/250 (0%) 1/125 (0.8%) 0/347 (0%)
    Osteitis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Osteoarthritis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Osteopenia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Osteoporosis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Spinal osteoarthritis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Tenosynovitis stenosans 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Bladder neoplasm 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Cervix carcinoma 1/250 (0.4%) 1/125 (0.8%) 0/347 (0%)
    Cholangiocarcinoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Colon cancer 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Colon neoplasm 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Craniopharyngioma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Endometrial adenocarcinoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Gastric cancer 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Gastrointestinal carcinoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Hepatocellular carcinoma 2/250 (0.8%) 0/125 (0%) 8/347 (2.3%)
    Leiomyoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Leukaemia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Liposarcoma 0/250 (0%) 1/125 (0.8%) 0/347 (0%)
    Lung adenocarcinoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lung cancer metastatic 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lung neoplasm malignant 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Metastases to peritoneum 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Metastatic gastric cancer 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Mixed hepatocellular cholangiocarcinoma 1/250 (0.4%) 0/125 (0%) 0/347 (0%)
    Nasopharyngeal cancer 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Non-small cell lung cancer 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Prostate cancer 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Salivary gland adenoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Uterine leiomyoma 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Nervous system disorders
    Cerebral infarction 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Diabetic neuropathy 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Epilepsy 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Facial neuralgia 0/250 (0%) 1/125 (0.8%) 0/347 (0%)
    Loss of consciousness 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Sciatica 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Subarachnoid haemorrhage 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Syncope 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Psychiatric disorders
    Agitation 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Bipolar disorder 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Delusional disorder, unspecified type 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Depression 0/250 (0%) 1/125 (0.8%) 2/347 (0.6%)
    Dissociative disorder 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Psychotic disorder 0/250 (0%) 0/125 (0%) 2/347 (0.6%)
    Schizophrenia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Schizophrenia, paranoid type 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Renal and urinary disorders
    Renal colic 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Renal failure 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Urogenital fistula 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Fibrocystic breast disease 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Ovarian cyst 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Ovarian cyst ruptured 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Bronchiectasis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Dyspnoea 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Hypoxia 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Lung disorder 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Vascular disorders
    Arteritis 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Haematoma 0/250 (0%) 1/125 (0.8%) 1/347 (0.3%)
    Hypertension 0/250 (0%) 0/125 (0%) 1/347 (0.3%)
    Other (Not Including Serious) Adverse Events
    Double-Blind TDF Double-Blind ADV Open-Label TDF
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 121/250 (48.4%) 61/125 (48.8%) 256/347 (73.8%)
    Gastrointestinal disorders
    Abdominal pain 11/250 (4.4%) 6/125 (4.8%) 25/347 (7.2%)
    Abdominal pain upper 22/250 (8.8%) 10/125 (8%) 36/347 (10.4%)
    Diarrhoea 16/250 (6.4%) 8/125 (6.4%) 31/347 (8.9%)
    Dyspepsia 6/250 (2.4%) 6/125 (4.8%) 23/347 (6.6%)
    Nausea 15/250 (6%) 6/125 (4.8%) 14/347 (4%)
    General disorders
    Fatigue 13/250 (5.2%) 9/125 (7.2%) 20/347 (5.8%)
    Influenza like illness 6/250 (2.4%) 2/125 (1.6%) 23/347 (6.6%)
    Immune system disorders
    Seasonal allergy 5/250 (2%) 1/125 (0.8%) 18/347 (5.2%)
    Infections and infestations
    Influenza 10/250 (4%) 3/125 (2.4%) 38/347 (11%)
    Nasopharyngitis 22/250 (8.8%) 12/125 (9.6%) 62/347 (17.9%)
    Upper respiratory tract infection 6/250 (2.4%) 5/125 (4%) 24/347 (6.9%)
    Injury, poisoning and procedural complications
    Procedural pain 11/250 (4.4%) 9/125 (7.2%) 11/347 (3.2%)
    Investigations
    Blood creatine phosphokinase increased 2/250 (0.8%) 5/125 (4%) 20/347 (5.8%)
    Creatinine renal clearance decreased 0/250 (0%) 1/125 (0.8%) 30/347 (8.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 16/250 (6.4%) 0/125 (0%) 38/347 (11%)
    Back pain 18/250 (7.2%) 7/125 (5.6%) 54/347 (15.6%)
    Osteopenia 1/250 (0.4%) 0/125 (0%) 30/347 (8.6%)
    Nervous system disorders
    Dizziness 11/250 (4.4%) 4/125 (3.2%) 18/347 (5.2%)
    Headache 26/250 (10.4%) 17/125 (13.6%) 49/347 (14.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 11/250 (4.4%) 4/125 (3.2%) 30/347 (8.6%)
    Oropharyngeal pain 7/250 (2.8%) 6/125 (4.8%) 23/347 (6.6%)
    Vascular disorders
    Hypertension 9/250 (3.6%) 5/125 (4%) 53/347 (15.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Institution and investigator may publish or present the results of the trial generated there with prior written consent of Gilead; or 2 years after the trial has ended at all institutions. Proposed publications/target venue must go to Gilead 30 days (manuscripts) or 15 days (abstracts/presentations) prior. Any Gilead confidential information in the document(s) must be deleted, or if requested publication delayed for up to 45 days to permit Gilead to obtain intellectual property protection.

    Results Point of Contact

    Name/Title Clinical Trial Disclosures
    Organization Gilead Sciences, Inc.
    Phone
    Email ClinicalTrialDisclosures@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT00117676
    Other Study ID Numbers:
    • GS-US-174-0102
    • 2004-005119-27
    First Posted:
    Jul 8, 2005
    Last Update Posted:
    Mar 7, 2017
    Last Verified:
    Jan 1, 2017