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

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT00116805
Collaborator
(none)
266
Enrollment
87
Locations
2
Arms
127
Actual Duration (Months)
3.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The 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 HBeAg-positive 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 :
266 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 HBeAg Positive Chronic Hepatitis B
Actual Study Start Date :
Jun 1, 2005
Actual Primary Completion Date :
May 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 Week 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 Alanine Aminotransferase (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 Week 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 e Antigen (HBeAg) Loss/Seroconversion at Week 48 [Baseline; Week 48]

      HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 48. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 48.

    20. Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96 [Baseline; Week 96]

      HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 96. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 96.

    21. Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion 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.

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

      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.

    23. Percentage of Participants With HBsAg Loss 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.

    24. 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, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.

    25. 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.

    26. 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.

    27. 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.

    28. 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.

    29. 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.

    30. 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.

    31. 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.

    32. 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.

    33. 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:

    A patient must meet all of the following inclusion criteria to be eligible for participation in this study:

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

    • 18 through 69 years of age, inclusive

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

    • HBeAg positive at screening

    • Alanine aminotransferase (ALT) levels > 2 × ULN and ≤ 10 × the upper limit of the normal range (ULN)

    • Serum HBV DNA > 1 million 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 96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment

    • Negative serum β-human chorionic gonadotropin (hCG)

    • Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for > 12 weeks

    • Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks

    • Willing and able to provide written informed consent

    • 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:

    A patient who meets any of the following exclusion criteria is not to be enrolled in this study:

    • Pregnant women, women who are breast feeding or 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; for males, condoms should be used and for females, a barrier contraception method should be used

    • 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), ie, α-fetoprotein >50 ng/mL

    • Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta 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 Orange California United States 92868
    2 Pasadena California United States 91105
    3 San Diego California United States 92105
    4 San Jose California United States 95116
    5 Miami Florida United States 33136
    6 Atlanta Georgia United States 30308
    7 Atlanta Georgia United States 30309
    8 Honolulu Hawaii United States 96817
    9 Baltimore Maryland United States 21229
    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 10021
    15 New York New York United States 10029
    16 New York New York United States 10032
    17 Fairfax Virginia United States 22031
    18 Falls Church Virginia United States 22042
    19 Richmond Virginia United States 23298
    20 Seattle Washington United States 98101
    21 Camperdown New South Wales Australia 2050
    22 Concord New South Wales Australia 2139
    23 Westmead New South Wales Australia 2145
    24 Woolloongabba Queensland Australia 4102
    25 Clayton Victoria Australia 3168
    26 Footscray Victoria Australia 3011
    27 Parkville Victoria Australia 3050
    28 Prahran Victoria Australia 3004
    29 Fitzroy Australia 3065
    30 Perth Australia 6000
    31 Sofia Bulgaria 1407
    32 Sofia Bulgaria 1431
    33 Varna Bulgaria 9010
    34 Calgary Alberta Canada T2N4Z6
    35 Vancouver British Columbia Canada V5Z1H2
    36 Winnepeg Manitoba Canada R3E3P4
    37 Toronto Ontario Canada M5G 2C4
    38 Toronto Ontario Canada M5T 2S8
    39 Brno Czech Republic 62500
    40 Hradec Kralove Czech Republic
    41 Prague Czech Republic 140 21
    42 Praha 6- Stresovice Czech Republic 169 02
    43 Clichy France 92110
    44 Grenoble France 38043
    45 Lille France 59037
    46 Lyon France 69317
    47 Nancy France 54500
    48 Paris France 75651
    49 Strasbourg France 67901
    50 Berlin Germany 10969
    51 Duesseldorf Germany 40237
    52 Dusseldorf Germany 40225
    53 Essen Germany 45122
    54 Hamburg Germany 20099
    55 Hannover Germany 30623
    56 Herne Germany 44623
    57 Homburg/Saar Germany 66421
    58 Kiel Germany 24105
    59 Mainz Germany 55131
    60 Munchen Germany 81377
    61 Tubingen Germany 72076
    62 Athens Greece 11526
    63 Thessaloniki Greece 54642
    64 Thessaloniki Greece 56429
    65 Bologna Italy 40138
    66 Rotterdam Netherlands 3015
    67 Auckland New Zealand
    68 Hamilton New Zealand
    69 Wellington New Zealand
    70 Whakatane New Zealand
    71 Bialystok Poland 15-540
    72 Bydgoszcz Poland 85-030
    73 Chorzow Poland 41-500
    74 Kielce Poland 25-317
    75 Krakow Poland 31-501
    76 Warszawa Poland 01-201
    77 Wroclaw Poland 50-136
    78 Barcelona Spain 08025
    79 Barcelona Spain 08035
    80 Barcelona Spain 08907
    81 Valencia Spain 46009
    82 Ankara Turkey 06100
    83 Bursa Turkey
    84 Istanbul Turkey
    85 Izmir Turkey
    86 Birmingham United Kingdom B15 2TH
    87 London United Kingdom NW1 2BU

    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:
    NCT00116805
    Other Study ID Numbers:
    • GS-US-174-0103
    • 2004-005120-41
    First Posted:
    Jul 1, 2005
    Last Update Posted:
    Mar 9, 2017
    Last Verified:
    Jan 1, 2017
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    tenofovir
    adefovir
    hepatitis B
    HBeAg Positive
    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 09 June 2005. The last study visit occurred on 28 January 2016.
    Pre-assignment Detail 603 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) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) in the open-label period. ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Period Title: Double-blind Period Through Week 48
    STARTED 176 90
    COMPLETED 165 85
    NOT COMPLETED 11 5
    Period Title: Double-blind Period Through Week 48
    STARTED 154 84
    COMPLETED 144 83
    NOT COMPLETED 10 1
    Period Title: Double-blind Period Through Week 48
    STARTED 144 83
    COMPLETED 133 74
    NOT COMPLETED 11 9
    Period Title: Double-blind Period Through Week 48
    STARTED 133 74
    COMPLETED 123 68
    NOT COMPLETED 10 6
    Period Title: Double-blind Period Through Week 48
    STARTED 123 68
    COMPLETED 110 64
    NOT COMPLETED 13 4
    Period Title: Double-blind Period Through Week 48
    STARTED 110 64
    COMPLETED 104 64
    NOT COMPLETED 6 0
    Period Title: Double-blind Period Through Week 48
    STARTED 104 64
    COMPLETED 98 57
    NOT COMPLETED 6 7
    Period Title: Double-blind Period Through Week 48
    STARTED 98 57
    COMPLETED 90 56
    NOT COMPLETED 8 1
    Period Title: Double-blind Period Through Week 48
    STARTED 59 30
    COMPLETED 57 30
    NOT COMPLETED 2 0
    Period Title: Double-blind Period Through Week 48
    STARTED 57 29
    COMPLETED 53 29
    NOT COMPLETED 4 0

    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 176 90 266
    Age (Count of Participants)
    <=18 years
    3
    1.7%
    1
    1.1%
    4
    1.5%
    Between 18 and 65 years
    173
    98.3%
    89
    98.9%
    262
    98.5%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    34
    (11.3)
    34
    (12.2)
    34
    (11.6)
    Sex: Female, Male (Count of Participants)
    Female
    57
    32.4%
    26
    28.9%
    83
    31.2%
    Male
    119
    67.6%
    64
    71.1%
    183
    68.8%
    Region of Enrollment (participants) [Number]
    United States
    30
    17%
    14
    15.6%
    44
    16.5%
    Greece
    1
    0.6%
    2
    2.2%
    3
    1.1%
    Spain
    7
    4%
    2
    2.2%
    9
    3.4%
    Turkey
    10
    5.7%
    4
    4.4%
    14
    5.3%
    Italy
    0
    0%
    1
    1.1%
    1
    0.4%
    United Kingdom
    6
    3.4%
    1
    1.1%
    7
    2.6%
    France
    11
    6.3%
    3
    3.3%
    14
    5.3%
    Czech Republic
    3
    1.7%
    5
    5.6%
    8
    3%
    Canada
    17
    9.7%
    10
    11.1%
    27
    10.2%
    Poland
    16
    9.1%
    8
    8.9%
    24
    9%
    Australia
    22
    12.5%
    6
    6.7%
    28
    10.5%
    Bulgaria
    17
    9.7%
    11
    12.2%
    28
    10.5%
    Germany
    20
    11.4%
    8
    8.9%
    28
    10.5%
    Netherlands
    6
    3.4%
    4
    4.4%
    10
    3.8%
    New Zealand
    10
    5.7%
    11
    12.2%
    21
    7.9%
    Baseline Alanine Aminotransferase (ALT) above the Upper Limit of the Normal (ULN) Range (participants) [Number]
    Yes
    169
    96%
    90
    100%
    259
    97.4%
    No
    7
    4%
    0
    0%
    7
    2.6%
    Prior Lamivudine or FTC Treatment (participants) [Number]
    Yes
    8
    4.5%
    1
    1.1%
    9
    3.4%
    No
    168
    95.5%
    89
    98.9%
    257
    96.6%
    Baseline Hepatitis B Deoxyribonucleic Acid (HBV DNA) (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    8.64
    (1.076)
    8.88
    (0.930)
    8.72
    (1.033)
    Baseline Knodell Necroinflammatory Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    8.3
    (2.11)
    8.5
    (2.07)
    8.4
    (2.09)

    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 10 mg
    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 176 90
    Number [percentage of participants]
    66.5
    37.8%
    12.2
    13.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments With a sample size of 160 subjects in the TDF group and 80 subjects in the ADV group, a two group large-sample normal approximation test of proportions with a one-sided 0.025 significance level would have 95% power to reject the null hypothesis that the TDF treatment was inferior to the ADV treatment (the difference in proportions was less than -0.080) in favor of the alternative hypothesis that the TDF treatment was not inferior.
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted (baseline ALT ≤ 4 x upper limit of the normal range [ULN] or > 4 x ULN) difference is 0.
    Method Z-test
    Comments 2-sided 95% confidence interval (CI), stratified by baseline ALT was used to evaluate difference between groups in proportion of complete responders.
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 54.1
    Confidence Interval (2-Sided) 95%
    44.6 to 63.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.8
    Estimation Comments
    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 176 90
    Number [percentage of participants]
    76.1
    43.2%
    13.3
    14.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    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 in zero.
    Method Z-test
    Comments Difference, standard error of the difference, and the CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 63.1
    Confidence Interval (2-Sided) 95%
    53.8 to 72.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.7
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With HBV DNA < 400 Copies/mL at Week 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 discontinued study unless the 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 165 86
    Number [percentage of participants]
    77.6
    44.1%
    77.9
    86.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.801
    Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference is zero.
    Method Z-test
    Comments Two-sided 95% CIs, stratified by baseline ALT (baseline ALT ≤ 4 x ULN or > 4 x ULN), were used to evaluate treatment group differences.
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -12.0 to 9.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.4
    Estimation Comments
    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 166 88
    Week 144
    71.7
    40.7%
    70.5
    78.3%
    Week 192
    67.9
    38.6%
    71.6
    79.6%
    Week 240
    63.4
    36%
    66.3
    73.7%
    Week 288
    61.3
    34.8%
    64.8
    72%
    Week 336
    59.4
    33.8%
    62.1
    69%
    Week 384
    56.1
    31.9%
    60.5
    67.2%
    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 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.
    Measure Participants 57 29
    Week 432
    93.0
    52.8%
    100.0
    111.1%
    Week 480
    98.0
    55.7%
    96.6
    107.3%
    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 160 85
    Week 48
    -6.17
    (1.067)
    -3.93
    (1.728)
    Week 96
    -6.26
    (1.137)
    -6.38
    (1.184)
    Week 144
    -6.32
    (1.098)
    -6.31
    (1.407)
    Week 192
    -6.30
    (1.203)
    -6.49
    (1.028)
    Week 240
    -6.22
    (1.217)
    -6.45
    (0.986)
    Week 288
    -6.27
    (1.248)
    -6.49
    (1.003)
    Week 336
    -6.35
    (1.208)
    -6.46
    (1.017)
    Week 384
    -6.38
    (1.167)
    -6.28
    (1.450)
    Week 432
    -6.13
    (1.306)
    -6.45
    (1.008)
    Week 480
    -6.18
    (1.300)
    -6.37
    (1.159)
    7. Secondary Outcome
    Title Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
    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 144 80
    Week 96
    -0.10
    (0.422)
    -2.43
    (1.724)
    Week 144
    -0.19
    (0.475)
    -2.27
    (1.866)
    Week 192
    -0.20
    (0.565)
    -2.41
    (1.662)
    Week 240
    -0.14
    (0.706)
    -2.49
    (1.599)
    Week 288
    -0.18
    (0.762)
    -2.62
    (1.679)
    Week 336
    -0.25
    (0.618)
    -2.59
    (1.622)
    Week 384
    -0.29
    (0.643)
    -2.34
    (1.821)
    Week 432
    -0.13
    (0.854)
    -2.32
    (1.694)
    Week 480
    -0.24
    (0.630)
    -2.16
    (1.882)
    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 176 90
    Yes
    74.4
    42.3%
    67.8
    75.3%
    No
    25.6
    14.5%
    32.2
    35.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.320
    Comments P-value corresponds to a Z-test of the null hypothesis that the stratum-adjusted difference in zero. Difference, standard error of the difference, and the CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 5.8
    Confidence Interval (2-Sided) 95%
    -5.6 to 17.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.8
    Estimation Comments
    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 76 48
    Yes
    88.2
    50.1%
    89.6
    99.6%
    No
    11.8
    6.7%
    10.4
    11.6%
    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 157 79
    Knodell Necroinflammatory Score
    -3.6
    (2.30)
    -3.2
    (2.35)
    Ishak Necroinflammatory Score
    -2.7
    (1.70)
    -2.6
    (1.94)
    11. Secondary Outcome
    Title Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
    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 76 48
    Knodell Necroinflammatory Score
    -4.8
    (2.34)
    -5.1
    (2.43)
    Ishak Necroinflammatory Score
    -4.1
    (2.14)
    -4.5
    (2.32)
    12. Secondary Outcome
    Title Ranked Assessment of Necroinflammation and Fibrosis at Week 48
    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 176 90
    Improvement - Necroinflammation
    81.3
    46.2%
    78.9
    87.7%
    No Change - Necroinflammation
    4.5
    2.6%
    3.3
    3.7%
    Worsening - Necroinflammation
    3.4
    1.9%
    5.6
    6.2%
    Missing Data - Necroinflammation
    10.8
    6.1%
    12.2
    13.6%
    Improvement - Fibrosis
    19.9
    11.3%
    20.0
    22.2%
    No Change - Fibrosis
    63.6
    36.1%
    61.1
    67.9%
    Worsening - Fibrosis
    5.1
    2.9%
    6.7
    7.4%
    Missing Data - Fibrosis
    11.4
    6.5%
    12.2
    13.6%
    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 76 48
    Improvement - Necroinflammation
    96.1
    54.6%
    97.9
    108.8%
    No Change - Necroinflammation
    3.9
    2.2%
    2.1
    2.3%
    Worsening - Necroinflammation
    0
    0%
    0
    0%
    Improvement - Fibrosis
    56.6
    32.2%
    58.3
    64.8%
    No Change - Fibrosis
    39.5
    22.4%
    39.6
    44%
    Worsening - Fibrosis
    3.9
    2.2%
    2.1
    2.3%
    14. Secondary Outcome
    Title Percentage of Participants With Alanine Aminotransferase (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 169 90
    Number [percentage of participants]
    68.0
    38.6%
    54.4
    60.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments P-value corresponds to a Z-test. Statistical tests were not adjusted for baseline ALT stratum.
    Method Z-test
    Comments Difference, standard error of the difference, and CI are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 13.6
    Confidence Interval (2-Sided) 95%
    1.1 to 26.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.4
    Estimation Comments
    15. Secondary Outcome
    Title Percentage of Participants With ALT Normalization at Week 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 158 86
    Number [percentage of participants]
    65.2
    37%
    74.4
    82.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.100
    Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero.
    Method Z-test
    Comments Difference, standard error of the difference, and CI are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.8
    Confidence Interval (2-Sided) 95%
    -21.5 to 1.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.0
    Estimation Comments
    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 161 87
    Week 144
    60.2
    34.2%
    67.8
    75.3%
    Week 192
    59.6
    33.9%
    69.4
    77.1%
    Week 240
    50.0
    28.4%
    65.9
    73.2%
    Week 288
    51.3
    29.1%
    70.1
    77.9%
    Week 336
    46.2
    26.3%
    67.9
    75.4%
    Week 384
    52.6
    29.9%
    67.1
    74.6%
    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 54 29
    Week 432
    79.6
    45.2%
    78.6
    87.3%
    Week 480
    75.0
    42.6%
    82.8
    92%
    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 160 84
    Week 48
    -107.2
    (109.44)
    -106.1
    (118.90)
    Week 96
    -107.8
    (108.07)
    -120.4
    (138.03)
    Week 144
    -100.7
    (105.96)
    -126.2
    (150.46)
    Week 192
    -101.4
    (108.63)
    -139.6
    (137.95)
    Week 240
    -95.9
    (117.03)
    -134.8
    (135.59)
    Week 288
    -102.3
    (111.68)
    -130.9
    (123.08)
    Week 336
    -101.9
    (112.72)
    -132.3
    (125.81)
    Week 384
    -108.1
    (118.05)
    -133.7
    (128.57)
    Week 432
    -105.0
    (139.61)
    -162.1
    (157.83)
    Week 480
    -92.3
    (83.56)
    -157.5
    (159.96)
    19. Secondary Outcome
    Title Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
    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 141 81
    Week 96
    -2.0
    (17.94)
    -6.9
    (59.64)
    Week 144
    -0.4
    (21.94)
    -0.7
    (82.70)
    Week 192
    -1.3
    (19.57)
    -7.8
    (27.07)
    Week 240
    3.7
    (32.48)
    -8.1
    (22.92)
    Week 288
    -1.6
    (19.91)
    -10.3
    (25.26)
    Week 336
    -1.2
    (19.72)
    -9.3
    (22.69)
    Week 384
    -4.4
    (24.87)
    -6.9
    (31.76)
    Week 432
    -4.3
    (24.27)
    -11.6
    (27.09)
    Week 480
    -5.5
    (19.28)
    -7.1
    (39.76)
    20. Secondary Outcome
    Title Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
    Description HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 48. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 48.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed.
    Arm/Group Title TDF-TDF ADV-TDF
    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 153 80
    HBeAg Loss
    22.2
    12.6%
    17.5
    19.4%
    HBeAg Seroconversion
    20.9
    11.9%
    17.5
    19.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to HBeAg loss.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.245
    Comments P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
    Method Z-test
    Comments Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 6.1
    Confidence Interval (2-Sided) 95%
    -4.2 to 16.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.3
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to HBeAg seroconversion.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.363
    Comments P-value for HBeAg seroconversion corresponds to Z-test of the null hypothesis that stratum-adjusted difference is zero.
    Method Z-test
    Comments Difference, standard error of difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 4.7
    Confidence Interval (2-Sided) 95%
    -5.5 to 14.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.2
    Estimation Comments
    21. Secondary Outcome
    Title Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
    Description HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 96. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 96.
    Time Frame Baseline; Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
    Arm/Group Title TDF-TDF ADV-TDF
    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 158 82
    HBeAg Loss
    25.9
    14.7%
    25.6
    28.4%
    Seroconversion to Anti-HBe
    22.8
    13%
    22.0
    24.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to HBeAg loss.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.963
    Comments P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
    Method Z-test
    Comments Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -11.3 to 11.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.9
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to seroconversion to anti-HBe.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.904
    Comments P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero.
    Method Z-test
    Comments Difference, standard error of the difference, and Cl are stratum adjusted based on baseline ALT category (≤ 4 x ULN or >4 x ULN).
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -10.4 to 11.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.6
    Estimation Comments
    22. Secondary Outcome
    Title Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion 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 with available data were analyzed.
    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 158 82
    HBsAg Loss
    3.2
    1.8%
    0
    0%
    HBsAg Seroconversion
    1.3
    0.7%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to HBsAg loss.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero. Difference, standard error of the difference, and confidence interval (CI) are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 10.9
    Confidence Interval (2-Sided) 95%
    1.9 to 19.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.6
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to HBsAg seroconversion.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.148
    Comments P-value corresponds to a Z-test of the null hypothesis that the ALT stratum-adjusted difference is zero. Difference, standard error of the difference, and confidence interval (CI) are stratum adjusted (baseline ALT ≤ 4 x ULN or > 4 x ULN).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 4.3
    Confidence Interval (2-Sided) 95%
    -1.5 to 10.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.0
    Estimation Comments
    23. Secondary Outcome
    Title Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
    Description HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
    Time Frame Baseline; Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
    Arm/Group Title TDF-TDF ADV-TDF
    Arm/Group Description TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    Measure Participants 171 86
    HBsAg Loss
    5.3
    3%
    5.8
    6.4%
    Anti-HBs Seroconversion
    4.1
    2.3%
    4.7
    5.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to HBsAg loss.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.757
    Comments P-value above for HBsAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero. Difference, standard error of the difference, and CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -4.8 to 6.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.9
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TDF-TDF, ADV 10 mg
    Comments This information pertains to seroconversion to anti-HBs.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.733
    Comments P-value above corresponds to Z-test of the null hypothesis that stratum-adjusted difference is zero. Difference, standard error of the difference, and CI are stratum adjusted based on baseline ALT category (≤ 4 x ULN or > 4 x ULN).
    Method Z-test
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -4.2 to 5.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.6
    Estimation Comments
    24. Secondary Outcome
    Title Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480
    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. 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.
    Measure Participants 174 89
    HBsAg Loss - Week 144
    7.5
    4.3%
    8.0
    8.9%
    Anti-HBs Seroconversion - Week 144
    5.2
    3%
    6.8
    7.6%
    HBsAg Loss - Week 192
    9.4
    5.3%
    7.9
    8.8%
    Anti-HBs Seroconversion - Week 192
    6.4
    3.6%
    6.7
    7.4%
    HBsAg Loss - Week 240
    9.2
    5.2%
    8.0
    8.9%
    Anti-HBs Seroconversion - Week 240
    6.3
    3.6%
    8.0
    8.9%
    HBsAg Loss - Week 288
    9.2
    5.2%
    8.0
    8.9%
    Anti-HBs Seroconversion - Week 288
    6.4
    3.6%
    8.0
    8.9%
    HBsAg Loss - Week 336
    10.3
    5.9%
    7.9
    8.8%
    Anti-HBs Seroconversion - Week 336
    7.5
    4.3%
    7.9
    8.8%
    HBsAg Loss - Week 384
    11.0
    6.3%
    9.0
    10%
    Anti-HBs Seroconversion - Week 384
    8.1
    4.6%
    7.9
    8.8%
    HBsAg Loss - Week 432
    10.9
    6.2%
    10.2
    11.3%
    Anti-HBs Seroconversion - Week 432
    7.6
    4.3%
    8.0
    8.9%
    HBsAg Loss - Week 480
    10.9
    6.2%
    10.1
    11.2%
    Anti-HBs Seroconversion - Week 480
    8.0
    4.5%
    7.9
    8.8%
    25. 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, 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 176 90
    Participants evaluated
    31
    17.6%
    75
    83.3%
    Changes at conserved sites in HBV polymerase
    2
    1.1%
    8
    8.9%
    Changes at polymorphic sites in HBV polymerase
    13
    7.4%
    17
    18.9%
    No genotypic changes (wild-type virus)
    7
    4%
    43
    47.8%
    Unable to be genotyped
    9
    5.1%
    7
    7.8%
    26. 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 154 15 84 13
    Participants evaluated
    18
    10.2%
    13
    14.4%
    16
    6%
    10
    NaN
    Changes at conserved sites in HBV polymerase
    2
    1.1%
    0
    0%
    2
    0.8%
    3
    NaN
    Changes at polymorphic sites in HBV polymerase
    3
    1.7%
    1
    1.1%
    1
    0.4%
    2
    NaN
    No genotypic changes (wild-type virus)
    10
    5.7%
    5
    5.6%
    12
    4.5%
    3
    NaN
    Unable to be genotyped
    3
    1.7%
    7
    7.8%
    1
    0.4%
    2
    NaN
    27. 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 126 17 69 13
    Participants evaluated
    2
    1.1%
    7
    7.8%
    5
    1.9%
    5
    NaN
    Changes at conserved sites in HBV polymerase
    1
    0.6%
    2
    2.2%
    2
    0.8%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    3
    3.3%
    3
    1.1%
    0
    NaN
    No genotypic changes (wild-type virus)
    1
    0.6%
    2
    2.2%
    0
    0%
    3
    NaN
    Unable to be genotyped
    0
    0%
    0
    0%
    0
    0%
    1
    NaN
    28. 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 115 15 61 10
    Participants evaluated
    2
    1.1%
    5
    5.6%
    1
    0.4%
    1
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    1
    0.6%
    0
    0%
    1
    0.4%
    1
    NaN
    No genotypic changes (wild-type virus)
    0
    0%
    1
    1.1%
    0
    0%
    0
    NaN
    Unable to be genotyped
    1
    0.6%
    3
    3.3%
    0
    0%
    0
    NaN
    29. 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 103 13 55 12
    Participants evaluated
    3
    1.7%
    3
    3.3%
    0
    0%
    1
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    1
    NaN
    Changes at polymorphic sites in HBV polymerase
    2
    1.1%
    0
    0%
    0
    0%
    0
    NaN
    No genotypic changes (wild-type virus)
    1
    0.6%
    2
    2.2%
    0
    0%
    0
    NaN
    Unable to be genotyped
    0
    0%
    1
    1.1%
    0
    0%
    0
    NaN
    30. 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 92 11 52 12
    Participants evaluated
    3
    1.7%
    0
    0%
    0
    0%
    0
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    No genotypic changes (wild-type virus)
    2
    1.1%
    0
    0%
    0
    0%
    0
    NaN
    Unable to be genotyped
    1
    0.6%
    0
    0%
    0
    0%
    0
    NaN
    31. 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 93 12 53 12
    Participants evaluated
    1
    0.6%
    0
    0%
    1
    0.4%
    0
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    No genotypic changes (wild-type virus)
    0
    0%
    0
    0%
    1
    0.4%
    0
    NaN
    Unable to be genotyped
    1
    0.6%
    0
    0%
    0
    0%
    0
    NaN
    32. 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 87 12 50 10
    Participants evaluated
    1
    0.6%
    0
    0%
    2
    0.8%
    2
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    1
    0.4%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    0
    0%
    1
    0.4%
    1
    NaN
    No genotypic changes (wild-type virus)
    0
    0%
    0
    0%
    0
    0%
    1
    NaN
    Unable to be genotyped
    1
    0.6%
    0
    0%
    0
    0%
    0
    NaN
    33. 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 49 10 26 4
    Participants evaluated
    1
    0.6%
    3
    3.3%
    0
    0%
    1
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    1
    0.6%
    0
    0%
    0
    0%
    0
    NaN
    No genotypic changes (wild-type virus)
    0
    0%
    3
    3.3%
    0
    0%
    1
    NaN
    Unable to be genotyped
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    34. 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 47 10 26 3
    Participants evaluated
    0
    0%
    3
    3.3%
    1
    0.4%
    0
    NaN
    Changes at conserved sites in HBV polymerase
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    Changes at polymorphic sites in HBV polymerase
    0
    0%
    1
    1.1%
    0
    0%
    0
    NaN
    No genotypic changes (wild-type virus)
    0
    0%
    2
    2.2%
    1
    0.4%
    0
    NaN
    Unable to be genotyped
    0
    0%
    0
    0%
    0
    0%
    0
    NaN

    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 480), regardless of which group they were randomized to in the double-blind period. TDF 300 mg + ADV placebo or ADV 10 mg + TDF placebo (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
    All Cause Mortality
    Double-Blind TDF Double-Blind ADV Open-Label TDF
    Affected / at Risk (%) # 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 15/176 (8.5%) 7/90 (7.8%) 41/238 (17.2%)
    Blood and lymphatic system disorders
    Thrombocytopenia 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Angina pectoris 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Ischaemic cardiomyopathy 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Myocarditis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Congenital, familial and genetic disorders
    Congenital anomaly in offspring 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Gastrointestinal disorders
    Inguinal hernia 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    General disorders
    Chest pain 0/176 (0%) 1/90 (1.1%) 1/238 (0.4%)
    Hepatobiliary disorders
    Cholecystitis chronic 0/176 (0%) 1/90 (1.1%) 0/238 (0%)
    Cholelithiasis 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Hepatitis 1/176 (0.6%) 0/90 (0%) 1/238 (0.4%)
    Infections and infestations
    Abscess soft tissue 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Diverticulitis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Epididymitis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Gastroenteritis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Groin abscess 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Hepatitis B 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Orchitis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Respiratory tract infection 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Sepsis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Skin infection 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Urinary tract infection 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/176 (0%) 1/90 (1.1%) 0/238 (0%)
    Lower limb fracture 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Procedural dizziness 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Skull fracture 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Subdural haematoma 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Ulna fracture 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Investigations
    Alanine aminotransferase increased 6/176 (3.4%) 4/90 (4.4%) 6/238 (2.5%)
    Aspartate aminotransferase increased 2/176 (1.1%) 1/90 (1.1%) 2/238 (0.8%)
    Blood creatine phosphokinase increased 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Glucose urine present 0/176 (0%) 0/90 (0%) 2/238 (0.8%)
    Metabolism and nutrition disorders
    Diabetes mellitus inadequate control 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 0/176 (0%) 1/90 (1.1%) 0/238 (0%)
    Osteoarthritis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Osteoporosis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Synovial cyst 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Colon adenoma 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Hepatic cancer 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Hepatic cancer metastatic 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Hepatic neoplasm 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Hepatocellular carcinoma 0/176 (0%) 0/90 (0%) 2/238 (0.8%)
    Hodgkin's disease 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Lung cancer metastatic 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Lymphoma 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Prostate cancer 0/176 (0%) 0/90 (0%) 2/238 (0.8%)
    Tonsillar neoplasm 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Nervous system disorders
    Diabetic neuropathy 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Facial spasm 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Seizure 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Subarachnoid haemorrhage 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Transient ischaemic attack 0/176 (0%) 0/90 (0%) 2/238 (0.8%)
    Psychiatric disorders
    Drug dependence 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Renal and urinary disorders
    Calculus ureteric 0/176 (0%) 0/90 (0%) 3/238 (1.3%)
    Tubulointerstitial nephritis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Reproductive system and breast disorders
    Ovarian cyst ruptured 1/176 (0.6%) 0/90 (0%) 0/238 (0%)
    Surgical and medical procedures
    Abortion induced 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    Vascular disorders
    Thrombosis 0/176 (0%) 0/90 (0%) 1/238 (0.4%)
    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 97/176 (55.1%) 49/90 (54.4%) 165/238 (69.3%)
    Gastrointestinal disorders
    Abdominal pain 6/176 (3.4%) 3/90 (3.3%) 22/238 (9.2%)
    Abdominal pain upper 15/176 (8.5%) 4/90 (4.4%) 25/238 (10.5%)
    Diarrhoea 12/176 (6.8%) 3/90 (3.3%) 12/238 (5%)
    Nausea 26/176 (14.8%) 1/90 (1.1%) 9/238 (3.8%)
    General disorders
    Fatigue 22/176 (12.5%) 8/90 (8.9%) 20/238 (8.4%)
    Influenza like illness 9/176 (5.1%) 3/90 (3.3%) 14/238 (5.9%)
    Immune system disorders
    Seasonal allergy 4/176 (2.3%) 1/90 (1.1%) 17/238 (7.1%)
    Infections and infestations
    Bronchitis 2/176 (1.1%) 4/90 (4.4%) 13/238 (5.5%)
    Influenza 8/176 (4.5%) 5/90 (5.6%) 25/238 (10.5%)
    Nasopharyngitis 22/176 (12.5%) 13/90 (14.4%) 43/238 (18.1%)
    Upper respiratory tract infection 7/176 (4%) 6/90 (6.7%) 21/238 (8.8%)
    Investigations
    Creatinine renal clearance decreased 1/176 (0.6%) 1/90 (1.1%) 12/238 (5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/176 (2.8%) 6/90 (6.7%) 17/238 (7.1%)
    Back pain 13/176 (7.4%) 3/90 (3.3%) 18/238 (7.6%)
    Musculoskeletal pain 2/176 (1.1%) 3/90 (3.3%) 15/238 (6.3%)
    Myalgia 8/176 (4.5%) 5/90 (5.6%) 11/238 (4.6%)
    Nervous system disorders
    Dizziness 12/176 (6.8%) 2/90 (2.2%) 11/238 (4.6%)
    Headache 31/176 (17.6%) 14/90 (15.6%) 30/238 (12.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 10/176 (5.7%) 5/90 (5.6%) 30/238 (12.6%)
    Oropharyngeal pain 8/176 (4.5%) 5/90 (5.6%) 18/238 (7.6%)
    Vascular disorders
    Hypertension 3/176 (1.7%) 1/90 (1.1%) 24/238 (10.1%)

    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:
    NCT00116805
    Other Study ID Numbers:
    • GS-US-174-0103
    • 2004-005120-41
    First Posted:
    Jul 1, 2005
    Last Update Posted:
    Mar 9, 2017
    Last Verified:
    Jan 1, 2017