Hepatitis B
Conditions
Keywords
Tenofovir DF, Emtricitabine, Chronic hepatitis B, Combination therapy
Brief summary
The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain suppression of viral replication to prevent the emergence of complications, which requires long-term therapy. Durable suppression of viral replication is achieved in the treatment of chronic viral diseases by preventing of the emergence of drug-resistant mutations. The clinical guidelines for the management of lamivudine resistant patients are variable. Some recommend switching to another agent without cross-resistance, while others recommend adding on another agent without cross-resistance. Limited clinical data exists to demonstrate whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for lamivudine resistant patients or if it should be used as part of a combination therapy regimen. This study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or without the rtL180M mutation) over a 240-week period. Participants in this study must be receiving lamivudine treatment at the time of enrollment.
Interventions
DRUGFTC/TDF
Emtricitabine (FTC)/TDF 200/300 mg fixed-dose combination tablet administered orally once daily
DRUGTDF Placebo
TDF placebo tablet administered orally once daily
DRUGFTC/TDF Placebo
FTC/TDF placebo tablet administered orally once daily
DRUGTDF
Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Chronic HBV infection, defined as positive serum HBsAg for at least 6 months * 18 through 75 years of age, inclusive * HBV DNA ≥ 10\^3 IU/mL * Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase mutation(s) known to confer resistance to lamivudine (rtM204I/V with or without rtL180M) by central laboratory assessment prior to randomization; adefovir dipivoxil treatment of ≤ 48 weeks at the time of screening (inclusive of combination adefovir dipivoxil + lamivudine at entry) was allowed * Willing and able to provide written informed consent * Negative serum pregnancy test (for females of childbearing potential only) * Calculated creatinine clearance ≥ 50 mL/min * Hemoglobin ≥ 10 g/dL * Neutrophils ≥ 1000 /mm\^3 * No prior oral HBV therapy with approved nucleotide and/or nucleoside therapy or other investigational agents for HBV infection other than lamivudine or adefovir dipivoxil
Exclusion criteria
* 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 not willing to use an effective method of contraception during the study * Alanine aminotransferase (ALT) ≥ 10 × the upper limit of the normal range (ULN) * Decompensated liver disease * Interferon or pegylated interferon therapy within 6 months of the screening visit * Alpha fetoprotein \> 50 ng/mL * Evidence of hepatocellular carcinoma * Coinfection with hepatitis C virus, HIV, or hepatitis D virus * Significant renal, cardiovascular, pulmonary, or neurological disease * Received solid organ or bone marrow transplantation * Receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion * Proximal tubulopathy * Known hypersensitivity to the study drugs, the metabolites or formulation excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96 | Week 96 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Weeks 48, 96, 144, 192, and 240 | — |
| HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Weeks 48, 96, 144, 192, and 240 | — |
| Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Weeks 48, 96, 144, 192, and 240 | Normal ALT was defined as having a value less than or equal to the ULN. 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. |
| Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Baseline; Weeks 48, 96, 144, 192, and 240 | The percentage of participants who were HBeAg positive at baseline and who had HBeAg Loss at the given time point was summarized. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. |
| Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Baseline; Weeks 48, 96, 144, 192, and 240 | The percentage of participants who were HBeAg positive at baseline and who had seroconversion to anti-HBe at the given time point was summarized. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive. |
| Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Weeks 48, 144, 192, and 240 | — |
| Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Baseline; Weeks 48, 96, 144, 192, and 240 | The percentage of participants with seroconversion to anti-HBs at the given time point was summarized. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive. |
| Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Baseline; Weeks 48, 96, 144, 192, and 240 | The percentage of participants with virologic breakthrough at the given time point was summarized. Virologic breakthrough was defined as having two consecutive 1.0 log10 or greater increases in serum HBV DNA from on-treatment nadir, or two consecutive HBV DNA values ≥ 400 copies/mL after being \< 400 copies/mL. |
| Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240 | BMD is calculated as grams per cubic centimeter (g/cm\^2); the mean (SD) percentage change is presented. |
| Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240 | BMD is calculated as g/cm\^2; the mean (SD) percentage change is presented. |
| Development of Drug-resistant Mutations (DRMs) | Baseline to Week 240 | The development of DRMs was summarized, either as development of new DRMs or enrichment of existing DRMs. |
| Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Baseline; Weeks 48, 96, 144, 192, and 240 | The percentage of participants with HBsAg Loss at the given time point was summarized. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. |
Countries
Austria, Bulgaria, Canada, Czechia, Germany, Greece, Hungary, New Zealand, Poland, Romania, Serbia, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, and New Zealand. The first participant was screened on 30 September 2008. The last study visit occurred on 09 February 2015.
Pre-assignment details
752 participants were screened. Randomization was stratified by hepatitis B e antigen (HBeAg) status (negative or positive) and alanine aminotransferase (ALT) level (≥ 2 × upper limit of normal \[ULN\] or \< 2 × ULN) at screening.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir DF TDF 300 mg tablet once daily plus FTC/TDF placebo tablet once daily | 141 |
| FTC/Tenofovir DF FTC/TDF 200/300 mg tablet once daily plus TDF placebo tablet once daily | 139 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment-Free Follow-up (TFFU) Period | Death | 0 | 1 |
| Treatment-Free Follow-up (TFFU) Period | Started Commercial Therapy | 25 | 17 |
| Treatment-Free Follow-up (TFFU) Period | Withdrew Consent | 1 | 0 |
| Treatment Period Through Week 240 | Investigator's Discretion | 6 | 5 |
| Treatment Period Through Week 240 | Lost to Follow-up | 3 | 3 |
| Treatment Period Through Week 240 | Protocol Violation | 2 | 3 |
| Treatment Period Through Week 240 | Safety, Tolerability, or Efficacy Reason | 3 | 4 |
| Treatment Period Through Week 240 | Study Discontinued by Sponsor | 1 | 0 |
| Treatment Period Through Week 240 | Withdrew Consent | 5 | 6 |
Baseline characteristics
| Characteristic | Tenofovir DF | FTC/Tenofovir DF | Total |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.63 | 46.3 years STANDARD_DEVIATION 13.56 | 46.7 years STANDARD_DEVIATION 13.58 |
| ALT Normal at Baseline Abnormal | 79 participants | 83 participants | 162 participants |
| ALT Normal at Baseline Normal | 62 participants | 56 participants | 118 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 138 Participants | 137 Participants | 275 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| HBV e Antigen (HBeAg) Status at Baseline Negative | 76 participants | 71 participants | 147 participants |
| HBV e Antigen (HBeAg) Status at Baseline Positive | 65 participants | 68 participants | 133 participants |
| Hepatitis B Virus (HBV) DNA Level at Baseline | 6.40 log_10 copies/mL STANDARD_DEVIATION 1.826 | 6.53 log_10 copies/mL STANDARD_DEVIATION 1.968 | 6.46 log_10 copies/mL STANDARD_DEVIATION 1.896 |
| Race/Ethnicity, Customized Asian | 52 participants | 42 participants | 94 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Other | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized White | 83 participants | 89 participants | 172 participants |
| Region of Enrollment Austria | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Bulgaria | 2 participants | 5 participants | 7 participants |
| Region of Enrollment Canada | 47 participants | 43 participants | 90 participants |
| Region of Enrollment Czech Republic | 9 participants | 7 participants | 16 participants |
| Region of Enrollment Germany | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Greece | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Hungary | 4 participants | 3 participants | 7 participants |
| Region of Enrollment New Zealand | 7 participants | 10 participants | 17 participants |
| Region of Enrollment Poland | 13 participants | 19 participants | 32 participants |
| Region of Enrollment Romania | 17 participants | 14 participants | 31 participants |
| Region of Enrollment Serbia | 17 participants | 19 participants | 36 participants |
| Region of Enrollment Spain | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Turkey | 15 participants | 13 participants | 28 participants |
| Region of Enrollment United States | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 37 Participants | 32 Participants | 69 Participants |
| Sex: Female, Male Male | 104 Participants | 107 Participants | 211 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 109 / 141 | 105 / 139 |
| serious Total, serious adverse events | 23 / 141 | 21 / 139 |
Outcome results
Primary
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Time frame: Week 96
Population: Full Analysis Set: participants were randomized and received at least 1 dose of study drug. The missing = failure method was used in which participants with missing data were considered to have failed to achieve the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96 | 89.4 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96 | 86.3 percentage of participants |
Comparison: The null hypothesis is that there is no difference between the FTC/TDF and TDF treatment groups. The alternative hypothesis is that there is a difference between the FTC/TDF and TDF treatment groups. These hypotheses were evaluated using a Cochran-Mantel-Haenszel (CMH) test, controlling for randomization strata, with the missing = failure method in which participants with missing data were considered to have failed to achieve the endpoint.p-value: 0.43Cochran-Mantel-Haenszel
Secondary
Development of Drug-resistant Mutations (DRMs)
The development of DRMs was summarized, either as development of new DRMs or enrichment of existing DRMs.
Time frame: Baseline to Week 240
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | New FTC DRMs | 0 participants |
| Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | New tenofovir DF DRMs | 0 participants |
| Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | Enrichment of FTC DRMs | 0 participants |
| Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | Enrichment of tenofovir DF DRMs | 0 participants |
| FTC/Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | Enrichment of FTC DRMs | 1 participants |
| FTC/Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | New tenofovir DF DRMs | 0 participants |
| FTC/Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | New FTC DRMs | 0 participants |
| FTC/Tenofovir DF | Development of Drug-resistant Mutations (DRMs) | Enrichment of tenofovir DF DRMs | 0 participants |
Secondary
HBV DNA Level at Weeks 48, 96, 144, 192, and 240
Time frame: Weeks 48, 96, 144, 192, and 240
Population: Full analysis set; participants with HBV DNA measurements at the given time point were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 96 (TDF: n=132; FTC/TDF: n=127) | 2.29 log10 copies/mL | Standard Deviation 0.254 |
| Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 192 (TDF: n=126; FTC/TDF: n=119) | 2.25 log10 copies/mL | Standard Deviation 0.135 |
| Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 144 (TDF: n=128; FTC/TDF: n=123) | 2.26 log10 copies/mL | Standard Deviation 0.173 |
| Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 240 (TDF: n=118; FTC/TDF: n=116) | 2.23 log10 copies/mL | Standard Deviation 0.052 |
| Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 48 (TDF: n=130; FTC/TDF: n=133) | 2.42 log10 copies/mL | Standard Deviation 0.542 |
| FTC/Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 240 (TDF: n=118; FTC/TDF: n=116) | 2.26 log10 copies/mL | Standard Deviation 0.376 |
| FTC/Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 48 (TDF: n=130; FTC/TDF: n=133) | 2.48 log10 copies/mL | Standard Deviation 0.887 |
| FTC/Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 96 (TDF: n=132; FTC/TDF: n=127) | 2.28 log10 copies/mL | Standard Deviation 0.241 |
| FTC/Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 144 (TDF: n=128; FTC/TDF: n=123) | 2.29 log10 copies/mL | Standard Deviation 0.541 |
| FTC/Tenofovir DF | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Week 192 (TDF: n=126; FTC/TDF: n=119) | 2.23 log10 copies/mL | Standard Deviation 0.027 |
Secondary
Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240
The percentage of participants who were HBeAg positive at baseline and who had HBeAg Loss at the given time point was summarized. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.
Time frame: Baseline; Weeks 48, 96, 144, 192, and 240
Population: Participants in the Full Analysis Set who were HBeAg positive at baseline were analyzed using the missing = failure method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 48 | 9.2 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 96 | 15.4 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 144 | 23.1 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 192 | 21.5 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 240 | 24.6 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 240 | 19.1 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 192 | 14.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 96 | 13.2 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 48 | 5.9 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | Week 144 | 17.6 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240
Time frame: Weeks 48, 96, 144, 192, and 240
Population: Full Analysis Set, missing = failure method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 96 | 85.8 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 192 | 85.1 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 144 | 86.5 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 240 | 81.6 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 48 | 76.6 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 240 | 82.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 48 | 77.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 96 | 83.5 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 144 | 84.9 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Week 192 | 84.2 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240
Time frame: Weeks 48, 144, 192, and 240
Population: Full Analysis Set, missing = failure method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 48 | 81.6 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 144 | 87.2 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 192 | 86.5 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 240 | 83.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 240 | 82.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 48 | 84.2 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 192 | 85.6 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Week 144 | 84.9 percentage of participants |
Secondary
Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240
The percentage of participants with HBsAg Loss at the given time point was summarized. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
Time frame: Baseline; Weeks 48, 96, 144, 192, and 240
Population: Full Analysis Set, missing = failure method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 96 | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 192 | 0.7 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 144 | 0.7 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 240 | 1.4 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 48 | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 240 | 2.9 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 48 | 0.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 96 | 0.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 144 | 1.4 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | Week 192 | 2.9 percentage of participants |
Secondary
Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240
Normal ALT was defined as having a value less than or equal to the ULN. 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: Weeks 48, 96, 144, 192, and 240
Population: Full Analysis Set, missing = failure method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 96 | 70.2 percentage of participants |
| Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 192 | 75.9 percentage of participants |
| Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 144 | 70.2 percentage of participants |
| Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 240 | 71.6 percentage of participants |
| Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 48 | 67.4 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 240 | 71.9 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 48 | 69.8 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 96 | 69.8 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 144 | 75.5 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Week 192 | 76.3 percentage of participants |
Secondary
Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240
The percentage of participants who were HBeAg positive at baseline and who had seroconversion to anti-HBe at the given time point was summarized. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline; Weeks 48, 96, 144, 192, and 240
Population: Participants in the Full Analysis Set who were HBeAg positive at baseline were analyzed using the missing = failure method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 96 | 10.8 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 192 | 10.8 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 144 | 12.3 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 240 | 12.3 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 48 | 6.2 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 240 | 10.3 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 48 | 4.4 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 96 | 10.3 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 144 | 11.8 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | Week 192 | 10.3 percentage of participants |
Secondary
Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240
The percentage of participants with seroconversion to anti-HBs at the given time point was summarized. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline; Weeks 48, 96, 144, 192, and 240
Population: Full Analysis Set, missing = failure method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 96 | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 192 | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 144 | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 240 | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 48 | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 240 | 0.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 48 | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 96 | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 144 | 0.7 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | Week 192 | 0.7 percentage of participants |
Secondary
Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240
The percentage of participants with virologic breakthrough at the given time point was summarized. Virologic breakthrough was defined as having two consecutive 1.0 log10 or greater increases in serum HBV DNA from on-treatment nadir, or two consecutive HBV DNA values ≥ 400 copies/mL after being \< 400 copies/mL.
Time frame: Baseline; Weeks 48, 96, 144, 192, and 240
Population: Full Analysis Set; the missing-equals-excluded method was used in which participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 96 (TDF: n=132; FTC/TDF: n=127) | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 192 (TDF: n=126; FTC/TDF: n=119) | 0.8 percentage of participants |
| Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 144 (TDF: n=128; FTC/TDF: n=123) | 0.8 percentage of participants |
| Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 240 (TDF: n=118; FTC/TDF: n=116) | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 48 (TDF: n=130; FTC/TDF: n=133) | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 240 (TDF: n=118; FTC/TDF: n=116) | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 48 (TDF: n=130; FTC/TDF: n=133) | 0.8 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 96 (TDF: n=132; FTC/TDF: n=127) | 0.0 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 144 (TDF: n=128; FTC/TDF: n=123) | 0.8 percentage of participants |
| FTC/Tenofovir DF | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | Week 192 (TDF: n=126; FTC/TDF: n=119) | 0.0 percentage of participants |
Secondary
Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240
BMD is calculated as g/cm\^2; the mean (SD) percentage change is presented.
Time frame: Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240
Population: Participants in the Safety Analysis Set with hip BMD measurements at the given time point were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 72 (TDF: n=121; FTC/TDF: n=115) | -1.59 percentage change | Standard Deviation 2.507 |
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 144 (TDF: n=120; FTC/TDF: n=107) | -2.02 percentage change | Standard Deviation 3.03 |
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 48 (TDF: n=126; FTC/TDF: n=118) | -1.15 percentage change | Standard Deviation 2.12 |
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 192 (TDF: n=116; FTC/TDF: n=105) | -2.33 percentage change | Standard Deviation 3.19 |
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 96 (TDF: n=125; FTC/TDF: n=112) | -1.70 percentage change | Standard Deviation 2.617 |
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 240 (TDF: n=111; FTC/TDF: n=100) | -2.46 percentage change | Standard Deviation 3.191 |
| Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 24 (TDF: n=130; FTC/TDF: n=127) | -0.71 percentage change | Standard Deviation 1.724 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 240 (TDF: n=111; FTC/TDF: n=100) | -2.63 percentage change | Standard Deviation 3.872 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 24 (TDF: n=130; FTC/TDF: n=127) | -0.59 percentage change | Standard Deviation 1.835 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 48 (TDF: n=126; FTC/TDF: n=118) | -1.00 percentage change | Standard Deviation 2.063 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 72 (TDF: n=121; FTC/TDF: n=115) | -1.61 percentage change | Standard Deviation 2.525 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 96 (TDF: n=125; FTC/TDF: n=112) | -1.77 percentage change | Standard Deviation 2.801 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 144 (TDF: n=120; FTC/TDF: n=107) | -1.91 percentage change | Standard Deviation 3.281 |
| FTC/Tenofovir DF | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 192 (TDF: n=116; FTC/TDF: n=105) | -2.41 percentage change | Standard Deviation 3.783 |
Secondary
Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240
BMD is calculated as grams per cubic centimeter (g/cm\^2); the mean (SD) percentage change is presented.
Time frame: Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240
Population: Participants in the Safety Analysis Set (randomized and received at least 1 dose of study drug) with spine BMD measurements at the given time point were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 72 (TDF: n=123; FTC/TDF: n=119) | -1.35 percentage change | Standard Deviation 3.337 |
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 144 (TDF: n=123; FTC/TDF: n=110) | -1.36 percentage change | Standard Deviation 3.81 |
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 48 (TDF: n=126; FTC/TDF: n=121) | -1.68 percentage change | Standard Deviation 3.094 |
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 192 (TDF: n=120; FTC/TDF: n=106) | -1.32 percentage change | Standard Deviation 4.237 |
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 96 (TDF: n=126; FTC/TDF: n=114) | -1.24 percentage change | Standard Deviation 3.761 |
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 240 (TDF: n=115; FTC/TDF: n=102) | -0.83 percentage change | Standard Deviation 4.49 |
| Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 24 (TDF: n=132; FTC/TDF: n=127) | -1.74 percentage change | Standard Deviation 2.867 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 240 (TDF: n=115; FTC/TDF: n=102) | -1.15 percentage change | Standard Deviation 5.13 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 24 (TDF: n=132; FTC/TDF: n=127) | -1.83 percentage change | Standard Deviation 2.565 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 48 (TDF: n=126; FTC/TDF: n=121) | -1.73 percentage change | Standard Deviation 2.944 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 72 (TDF: n=123; FTC/TDF: n=119) | -1.95 percentage change | Standard Deviation 2.977 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 96 (TDF: n=126; FTC/TDF: n=114) | -1.72 percentage change | Standard Deviation 3.269 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 144 (TDF: n=123; FTC/TDF: n=110) | -1.63 percentage change | Standard Deviation 3.591 |
| FTC/Tenofovir DF | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | % Change at Week 192 (TDF: n=120; FTC/TDF: n=106) | -1.60 percentage change | Standard Deviation 4.628 |