Chronic Hepatitis B
Conditions
Keywords
tenofovir, monotherapy, emtricitabine, combination, hepatitis B
Brief summary
The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection. The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters. Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.
Interventions
DRUGTenofovir DF
Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily
DRUGFTC
Emtricitabine (FTC) 200 mg capsule taken orally once daily
DRUGPlacebo
Placebo to match FTC taken once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive \> 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen * 18 through 69 years of age, inclusive * Hepatitis B e antigen (HBeAg) positive * HBV DNA ≥ 10\^8 copies/mL * ALT ≤ the upper limit of the normal range (ULN) * Willing and able to provide written informed consent * Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only) * Calculated creatinine clearance ≥ 70 mL/min * Hemoglobin ≥ 10 g/dL * Neutrophils ≥ 1,500/mm\^3 * No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
Exclusion criteria
* Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study * Males and females of reproductive potential unwilling to use an effective method of contraception during the study * Decompensated liver disease defined as direct (conjugated) bilirubin \> 1.2 x ULN, prothrombin time \> 1.2 x ULN, platelets \< 150,000/mm\^3, serum albumin \< 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage) * Received interferon (pegylated or not) therapy within 6 months of the screening visit * Alpha-fetoprotein \> 50 ng/mL * Evidence of hepatocellular carcinoma * Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus * Significant renal, cardiovascular, pulmonary, or neurological disease * Received solid organ or bone marrow transplantation * Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion * Had proximal tubulopathy * Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 | Week 192 | The percentage of participants with HBV DNA \< 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Weeks 48, 96, 144, and 192 | The percentage of participants with HBV DNA \< 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation. |
| Change From Baseline in HBV DNA at Week 48 | Baseline to Week 48 | The change from baseline in HBV DNA at Week 48 was analyzed. |
| Change From Baseline in HBV DNA at Week 96 | Baseline to Week 96 | The change from baseline in HBV DNA at Week 96 was analyzed. |
| Change From Baseline in HBV DNA at Week 144 | Baseline to Week 144 | The change from baseline in HBV DNA at Week 144 was analyzed. |
| Change From Baseline in HBV DNA at Week 192 | Baseline to Week 192 | The change from baseline in HBV DNA at Week 192 was analyzed. |
| Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Weeks 48, 96, and 144 | The percentage of participants with HBV DNA \< 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation. |
| Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Weeks 48, 96, 144, and 192 | The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point. |
| Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Weeks 48, 96, 144, and 192 | The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point. |
| Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Weeks 48, 96, 144, and 192 | The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. |
| Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Weeks 48, 96, 144, and 192 | The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive. |
| Occurrence of HBV Resistance Mutations | Baseline to Week 192 | The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192). |
| Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Weeks 48, 96, 144, and 192 | Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation. |
Countries
Australia, Canada, France, Germany, Hong Kong, New Zealand, Poland, Singapore, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 34 sites in the North America, Europe, Asia, Australia, and New Zealand. The first participant was screened on 04 September 2007. The last participant observation for the Week 192 analysis was on 03 February 2012.
Pre-assignment details
309 participants were screened and 129 were randomized; 126 randomized participants received at least one dose of study drug, and comprise the Safety Analysis Set and the Full Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir DF Participants were randomized to receive tenofovir DF (300 mg tablet) plus placebo to match FTC (tablet) orally once daily. | 64 |
| FTC+Tenofovir DF Participants were randomized to receive FTC (200 mg tablet) plus tenofovir DF (300 mg tablet) orally once daily. | 62 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 24-week Treatment-free Follow-up Period | Adverse Event | 0 | 1 |
| 24-week Treatment-free Follow-up Period | Physician Decision | 1 | 0 |
| 24-week Treatment-free Follow-up Period | Withdrawal by Subject | 9 | 16 |
| Treatment Period | Adverse Event | 1 | 1 |
| Treatment Period | Lost to Follow-up | 0 | 2 |
| Treatment Period | Physician Decision | 4 | 1 |
| Treatment Period | Protocol Violation | 1 | 2 |
| Treatment Period | Withdrawal by Subject | 46 | 47 |
Baseline characteristics
| Characteristic | Total | Tenofovir DF | FTC+Tenofovir DF |
|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 10.3 | 33 years STANDARD_DEVIATION 9.5 | 33 years STANDARD_DEVIATION 11.2 |
| Alanine Aminotransferase (ALT) | 26.6 U/L STANDARD_DEVIATION 12.13 | 26.9 U/L STANDARD_DEVIATION 14.05 | 26.2 U/L STANDARD_DEVIATION 9.88 |
| Antibody to HBeAg (Anti-HBe) Missing/Unevaluable | 124 participants | 63 participants | 61 participants |
| Antibody to HBeAg (Anti-HBe) Negative | 1 participants | 0 participants | 1 participants |
| Antibody to HBeAg (Anti-HBe) Positive | 1 participants | 1 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 126 Participants | 64 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hepatitis B e Antigen (HBeAg) Negative | 1 participants | 1 participants | 0 participants |
| Hepatitis B e Antigen (HBeAg) Positive | 125 participants | 63 participants | 62 participants |
| Hepatitis B Virus (HBV) DNA | 9.17 log_10 copies/mL STANDARD_DEVIATION 0.397 | 9.18 log_10 copies/mL STANDARD_DEVIATION 0.402 | 9.16 log_10 copies/mL STANDARD_DEVIATION 0.395 |
| Race/Ethnicity, Customized Asian | 112 participants | 56 participants | 56 participants |
| Race/Ethnicity, Customized Black | 4 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Pacific Islander | 4 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized White | 5 participants | 4 participants | 1 participants |
| Region of Enrollment Australia | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Canada | 7 participants | 4 participants | 3 participants |
| Region of Enrollment France | 7 participants | 4 participants | 3 participants |
| Region of Enrollment Germany | 6 participants | 3 participants | 3 participants |
| Region of Enrollment Hong Kong | 61 participants | 28 participants | 33 participants |
| Region of Enrollment New Zealand | 6 participants | 2 participants | 4 participants |
| Region of Enrollment Poland | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Singapore | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Taiwan | 12 participants | 6 participants | 6 participants |
| Region of Enrollment United Kingdom | 2 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 22 participants | 14 participants | 8 participants |
| Sex: Female, Male Female | 64 Participants | 33 Participants | 31 Participants |
| Sex: Female, Male Male | 62 Participants | 31 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 64 | 39 / 62 | 2 / 26 | 7 / 29 |
| serious Total, serious adverse events | 6 / 64 | 3 / 62 | 0 / 26 | 0 / 29 |
Outcome results
Primary
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
The percentage of participants with HBV DNA \< 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time frame: Week 192
Population: Full Analysis Set: participants who were randomized and received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 | 54.7 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 | 75.8 percentage of participants |
Comparison: The null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 400 copies/mL at Week 192 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference. The sample size provided at least 85% power to detect a difference of 30% between the groups, assuming response rates of 30% and 60% in the Tenofovir DF and FTC+Tenofovir DF groups, respectively.p-value: 0.016Fisher Exact
Secondary
Change From Baseline in HBV DNA at Week 144
The change from baseline in HBV DNA at Week 144 was analyzed.
Time frame: Baseline to Week 144
Population: Participants in the Full Analysis Set with evaluable change data at Week 96 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenofovir DF | Change From Baseline in HBV DNA at Week 144 | -6.66 log_10 copies/mL | Standard Deviation 0.655 |
| FTC+Tenofovir DF | Change From Baseline in HBV DNA at Week 144 | -6.62 log_10 copies/mL | Standard Deviation 1.318 |
Comparison: The null hypothesis was that there was no difference of change in HBV DNA from baseline between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.186Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in HBV DNA at Week 192
The change from baseline in HBV DNA at Week 192 was analyzed.
Time frame: Baseline to Week 192
Population: Participants in the Full Analysis Set with evaluable change data at Week 96 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenofovir DF | Change From Baseline in HBV DNA at Week 192 | -6.32 log_10 copies/mL | Standard Deviation 1.463 |
| FTC+Tenofovir DF | Change From Baseline in HBV DNA at Week 192 | -6.70 log_10 copies/mL | Standard Deviation 0.913 |
Comparison: The null hypothesis was that there was no difference of change in HBV DNA from baseline between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.07Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in HBV DNA at Week 48
The change from baseline in HBV DNA at Week 48 was analyzed.
Time frame: Baseline to Week 48
Population: Participants in the Full Analysis Set with evaluable change data at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenofovir DF | Change From Baseline in HBV DNA at Week 48 | -6.22 log_10 copies/mL | Standard Deviation 0.608 |
| FTC+Tenofovir DF | Change From Baseline in HBV DNA at Week 48 | -6.49 log_10 copies/mL | Standard Deviation 0.577 |
Comparison: The null hypothesis was that there was no difference of change in HBV DNA from baseline between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.01Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in HBV DNA at Week 96
The change from baseline in HBV DNA at Week 96 was analyzed.
Time frame: Baseline to Week 96
Population: Participants in the Full Analysis Set with evaluable change data at Week 96 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenofovir DF | Change From Baseline in HBV DNA at Week 96 | -6.46 log_10 copies/mL | Standard Deviation 0.763 |
| FTC+Tenofovir DF | Change From Baseline in HBV DNA at Week 96 | -6.55 log_10 copies/mL | Standard Deviation 1.176 |
Comparison: The null hypothesis was that there was no difference of change in HBV DNA from baseline between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.019Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192
The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Time frame: Weeks 48, 96, 144, and 192
Population: Participants in the Full Analysis Set who were HBeAg positive at baseline were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 96 | 2 participants |
| Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 144 | 4 participants |
| Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 192 | 4 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 192 | 1 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 144 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 | Week 96 | 0 participants |
Comparison: Analysis at Week 96: the null hypothesis was that there was no difference in the proportion of subjects with HBeAg loss between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.496Fisher Exact
Comparison: Analysis at Week 144: the null hypothesis was that there was no difference in the proportion of subjects with HBeAg loss between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.119Fisher Exact
Comparison: Analysis at Week 192: the null hypothesis was that there was no difference in the proportion of subjects with HBeAg loss between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.365Fisher Exact
Secondary
Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192
The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
Time frame: Weeks 48, 96, 144, and 192
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 96 | 0 participants |
| Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 144 | 0 participants |
| Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 192 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 192 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 144 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 | Week 96 | 0 participants |
Secondary
Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192
Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time frame: Weeks 48, 96, 144, and 192
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 48 | 52 participants |
| Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 96 | 52 participants |
| Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 144 | 51 participants |
| Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 192 | 41 participants |
| FTC+Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 192 | 44 participants |
| FTC+Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 48 | 54 participants |
| FTC+Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 144 | 46 participants |
| FTC+Tenofovir DF | Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 | Week 96 | 50 participants |
Comparison: Analysis at Week 48: the null hypothesis was that there was no difference in the proportion of subjects with normal ALT at Week 48 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.467Fisher Exact
Comparison: Analysis at Week 96: the null hypothesis was that there was no difference in the proportion of subjects with normal ALT at Week 96 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 1Fisher Exact
Comparison: Analysis at Week 144: the null hypothesis was that there was no difference in the proportion of subjects with normal ALT at Week 144 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.529Fisher Exact
Comparison: Analysis at Week 192: the null hypothesis was that there was no difference in the proportion of subjects with normal ALT at Week 192 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.451Fisher Exact
Secondary
Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192
The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Time frame: Weeks 48, 96, 144, and 192
Population: Participants in the Full Analysis Set who were HBeAg positive at baseline were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 96 | 2 participants |
| Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 144 | 4 participants |
| Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 192 | 3 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 192 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 144 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 | Week 96 | 0 participants |
Comparison: Analysis at Week 96: the null hypothesis was that there was no difference in the proportion of subjects with seroconversion to anti-HBe between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.496Fisher Exact
Comparison: Analysis at Week 144: the null hypothesis was that there was no difference in the proportion of subjects with seroconversion to anti-HBe between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.119Fisher Exact
Comparison: Analysis at Week 192: the null hypothesis was that there was no difference in the proportion of subjects with seroconversion to anti-HBe between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.244Fisher Exact
Secondary
Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192
The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Weeks 48, 96, 144, and 192
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 96 | 0 participants |
| Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 144 | 0 participants |
| Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 192 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 192 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 48 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 144 | 0 participants |
| FTC+Tenofovir DF | Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 | Week 96 | 0 participants |
Secondary
Occurrence of HBV Resistance Mutations
The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192).
Time frame: Baseline to Week 192
Population: Genotyping was attempted for all participants with HBV DNA ≥ 400 copies/mL at Week 48, 96, 144, 192 and/or the early discontinuation visit, and for all participants (with HBV DNA ≥ 400 copies/mL) after Week 192 who were on study for at least 216 weeks when the last participant reached Week 192.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Occurrence of HBV Resistance Mutations | Conserved (with/without polymorphic) site changes | 6 participants |
| Tenofovir DF | Occurrence of HBV Resistance Mutations | Polymorphic site changes only | 16 participants |
| FTC+Tenofovir DF | Occurrence of HBV Resistance Mutations | Conserved (with/without polymorphic) site changes | 5 participants |
| FTC+Tenofovir DF | Occurrence of HBV Resistance Mutations | Polymorphic site changes only | 9 participants |
Secondary
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192
The percentage of participants with HBV DNA \< 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time frame: Weeks 48, 96, 144, and 192
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 48 | 29.7 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 96 | 45.3 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 144 | 50.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 192 | 45.3 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 192 | 69.4 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 48 | 33.9 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 144 | 72.6 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 | Week 96 | 64.5 percentage of participants |
Comparison: Analysis at Week 48: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 169 copies/mL at Week 48 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.703Fisher Exact
Comparison: Analysis at Week 96: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 169 copies/mL at Week 96 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.034Fisher Exact
Comparison: Analysis at Week 144: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 169 copies/mL at Week 144 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.011Fisher Exact
Comparison: Analysis at Week 192: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 169 copies/mL at Week 192 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.007Fisher Exact
Secondary
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144
The percentage of participants with HBV DNA \< 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time frame: Weeks 48, 96, and 144
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Week 48 | 40.6 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Week 96 | 53.1 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Week 144 | 62.5 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Week 48 | 59.7 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Week 96 | 75.8 percentage of participants |
| FTC+Tenofovir DF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 | Week 144 | 80.6 percentage of participants |
Comparison: Analysis at Week 48: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 400 copies/mL at Week 48 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.05Fisher Exact
Comparison: Analysis at Week 96: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 400 copies/mL at Week 96 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.009Fisher Exact
Comparison: Analysis at Week 144: the null hypothesis was that there was no difference in the proportion of subjects with HBV DNA \< 400 copies/mL at Week 144 between the Tenofovir DF and FTC+Tenofovir DF groups; the alternative hypothesis was that there was a difference.p-value: 0.03Fisher Exact