Chronic Hepatitis B
Conditions
Brief summary
Entecavir, 0.5 mg daily, will have clinical efficacy (assessed as an undetectable hepatitis B DNA, \<300 copies/mL, by Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction assay) that is comparable (noninferior) and potentially superior to lamivudine, 100 mg once daily, in adults with hepatitis B e antigen-negative chronic hepatitis B virus infection.
Interventions
DRUGEntecavir
Tablets, Oral, 0.5 mg, once daily (0-96 weeks) and (96-240 weeks)
DRUGLamivudine Placebo
Capsules, Oral, 0 mg, once daily (0-96 weeks)
DRUGLamivudine
Capsules, Oral, 100 mg, once daily (0-96 weeks) Tablets, Oral, 100 mg, once daily (96-240 weeks)
DRUGEntecavir Placebo
Tablets, Oral, 0 mg, once daily (0-96 weeks)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Nucleoside and nucleotide-naive subjects with chronic HBV infection * Hepatitis B Surface antigen(HBsAg)-positive ≥6 months * Detectable HBsAg * HBV DNA ≥ 105 copies/mL by PCR * ALT 1.3 to 10 x the ULN * HBeAg negative, anti-hepatitis B Virus E antigen antibody (anti-HBeAb) positive status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Virologic Response at Week 24 | At Week 24 | Virologic response=Hepatitis B virus DNA \<300 copies/mL by polymerase chain reaction assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At Weeks 24, 48, 96, 144, 192, and 240 | Mean log10 reduction from Baseline in HBV DNA virus by the Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction (PCR) assay at Week 24. The extent of the decrease was estimated by comparing HBV DNA levels of all participants in each group with a linear regression model with covariates of treatment and baseline HBV DNA by PCR assay. |
| Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24 | At Week 24 | Mean ALT values from baseline by laboratory test. . |
| Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At Weeks 24, 48, and 96 | Normalization of serum ALT= ≤\*institutional upper limit of normal. |
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Most common AEs=AEs affecting ≥3 participants. Grade 3 (Severe)/Grade 4 (Very Severe)AEs per World Health Organization (WHO) criteria.Serious adverse events/deaths reported for enrolled patients regardless of treatment status. |
| Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | Start of dosing (Day 1) until end of treatment (24 weeks) + 5 days and to end of 24-week follow-up period | ALT flares=ALT\>2\*Baseline and 10\*upper limit of normal. Serious adverse events/deaths reported for enrolled patients regardless of treatment status. |
| Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to the end of the 24-week follow-up period | ULN=upper limit of normal; ALT=alanine transaminase. WHO criteria: Grade 3=Severe (inability to carry out usual activity); Grade 4=Very severe (debilitating or significantly incapacitating patient despite symptomatic treatment). |
| Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | At Weeks 24, 48, and 96 | The number and percentage of participants achieving the following endpoints will be tabulated at each visit through Week 240 by treatment group: HBV DNA \<300 copies/mL by PCR assay; HBV DNA \<10\^3, \<10\^4, or \< 10\^5 copies/mL by PCR assay. Treatment comparisons will be assessed using the same method as the primary endpoint. |
| Number of Participants With Virologic Rebound at Week 24 | At Week 24 | Virologic rebound was defined as a confirmed ≥1 log10 increase in hepatitis B virus (HBV) DNA from nadir on blinded treatment (as determined by 2 sequential HBV DNA measurements or last on-treatment measurement). |
| Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At Weeks 48, 96, 144, 192, and 240 | Undetectable HBV DNA= \<300 copies/mL by polymerase chain reaction assay |
| Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 | At 96 weeks | Virologic rebound was defined as a confirmed ≥1 log10 increase in HBV DNA from nadir on blinded treatment (as determined by 2 sequential HBV DNA values or last on-treatment measurement). |
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Start of dosing (Day 1) until end of treatment (Week 240) + 5 days | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Start of dosing (Day 1) until Week 96 | ULN=upper limit of normal; ALT=alanine transaminase. WHO criteria: Grade 3=Severe (inability to carry out usual activity); Grade 4=Very severe (debilitating or significantly incapacitating patient despite symptomatic treatment). |
| Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24 | Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period | Vital signs assessed included blood pressure, heart rate, body temperature, and respiration rate. |
Countries
South Korea
Participant flow
Pre-assignment details
A total of 122 participants were enrolled in this study; 2 did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Entecavir, 0.5 mg + Placebo Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period). | 56 |
| Lamivudine, 100 mg + Placebo Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period). | 64 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period (Day 1 to Week 96) | Adverse Event | 0 | 1 |
| Double-blind Period (Day 1 to Week 96) | Lack of Efficacy | 0 | 6 |
| Double-blind Period (Day 1 to Week 96) | Lost to Follow-up | 0 | 2 |
| Double-blind Period (Day 1 to Week 96) | No longer met inclusion criteria | 0 | 3 |
| Double-blind Period (Day 1 to Week 96) | Withdrawal by Subject | 2 | 0 |
| Open-label Period (Weeks 96 to 240) | Death | 1 | 0 |
| Open-label Period (Weeks 96 to 240) | Lack of Efficacy | 0 | 18 |
| Open-label Period (Weeks 96 to 240) | Lost to Follow-up | 1 | 2 |
| Open-label Period (Weeks 96 to 240) | Noncompliance | 2 | 2 |
| Open-label Period (Weeks 96 to 240) | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Entecavir, 0.5 mg + Placebo | Lamivudine, 100 mg + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.73 years STANDARD_DEVIATION 11.93 | 48.98 years STANDARD_DEVIATION 7.84 | 47.46 years STANDARD_DEVIATION 10.05 |
| Alanine aminotransferase | 110.46 U/L STANDARD_DEVIATION 81.97 | 93.94 U/L STANDARD_DEVIATION 58.46 | 101.65 U/L STANDARD_DEVIATION 70.59 |
| Hepatitis B virus DNA by polymerase chain reaction | 6.06 log10 copies/mL STANDARD_DEVIATION 0.78 | 5.79 log10 copies/mL STANDARD_DEVIATION 0.9 | 5.91 log10 copies/mL STANDARD_DEVIATION 0.86 |
| Prior interferon treatment status No | 54 Participants | 64 Participants | 118 Participants |
| Prior interferon treatment status Yes | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Korea, Republic of | 56 participants | 64 participants | 120 participants |
| Sex: Female, Male Female | 9 Participants | 16 Participants | 25 Participants |
| Sex: Female, Male Male | 47 Participants | 48 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 56 | 29 / 64 |
| serious Total, serious adverse events | 7 / 56 | 17 / 64 |
Outcome results
Primary
Percentage of Participants Who Achieved a Virologic Response at Week 24
Virologic response=Hepatitis B virus DNA \<300 copies/mL by polymerase chain reaction assay.
Time frame: At Week 24
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir, 0.5 mg + Placebo | Percentage of Participants Who Achieved a Virologic Response at Week 24 | 92.86 Percentage of participants |
| Lamivudine, 100 mg + Placebo | Percentage of Participants Who Achieved a Virologic Response at Week 24 | 67.19 Percentage of participants |
Comparison: A sample size of 60 per group provides 80% power for testing superiority of entecavir compared to lamivudine, assuming a response rate of 62% for lamivudine and 83% for entecavir.p-value: 0.000690% CI: [14.48, 36.86]Chi-squared
Secondary
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24
Mean ALT values from baseline by laboratory test. .
Time frame: At Week 24
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24 | 31.5 U/L | Standard Deviation 14.04 |
| Lamivudine, 100 mg + Placebo | Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24 | 43.26 U/L | Standard Deviation 32.08 |
Secondary
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
Mean log10 reduction from Baseline in HBV DNA virus by the Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction (PCR) assay at Week 24. The extent of the decrease was estimated by comparing HBV DNA levels of all participants in each group with a linear regression model with covariates of treatment and baseline HBV DNA by PCR assay.
Time frame: At Weeks 24, 48, 96, 144, 192, and 240
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 24 Weeks | 3.58 log10 copies/mL | Standard Deviation 0.6 |
| Entecavir, 0.5 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 48 Weeks | 3.56 log10 copies/mL | Standard Deviation 0.53 |
| Entecavir, 0.5 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 96 Weeks | 3.59 log10 copies/mL | Standard Deviation 0.52 |
| Entecavir, 0.5 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 144 Weeks | -3.60 log10 copies/mL | Standard Deviation 0.6 |
| Entecavir, 0.5 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 192 Weeks | -3.60 log10 copies/mL | Standard Deviation 0.63 |
| Entecavir, 0.5 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 240 Weeks | -3.53 log10 copies/mL | Standard Deviation 0.85 |
| Lamivudine, 100 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 192 Weeks | -2.75 log10 copies/mL | Standard Deviation 0.73 |
| Lamivudine, 100 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 24 Weeks | 2.95 log10 copies/mL | Standard Deviation 0.69 |
| Lamivudine, 100 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 144 Weeks | -2.74 log10 copies/mL | Standard Deviation 0.7 |
| Lamivudine, 100 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 48 Weeks | 2.65 log10 copies/mL | Standard Deviation 0.61 |
| Lamivudine, 100 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 240 Weeks | -2.69 log10 copies/mL | Standard Deviation 0.98 |
| Lamivudine, 100 mg + Placebo | Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 | At 96 Weeks | 2.42 log10 copies/mL | Standard Deviation 0.6 |
Comparison: Changes from baseline were based on patients with measurements at both Baseline and Week 24.p-value: <0.0001unpaired t-test
Comparison: Changes from Baseline were based on patients with measurements at both Baseline and at Week 48.p-value: <0.0001unpaired t-test
Comparison: Changes from Baseline were based on patients with measurements at both Baseline and at 96 Weeks.p-value: <0.0001unpaired t-test
Comparison: Changes from Baseline were based on patients with measurements at both Baseline and at Week 144.p-value: <0.0001unpaired t-test
Comparison: Changes from Baseline were based on patients with measurements at both Baseline and at Week 192.p-value: <0.0001unpaired t-test
Comparison: Changes from Baseline were based on patients with measurements at both Baseline and at Week 240.p-value: <0.0001unpaired t-test
Secondary
Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24
Vital signs assessed included blood pressure, heart rate, body temperature, and respiration rate.
Time frame: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24 | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24 | 0 Participants |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Most common AEs=AEs affecting ≥3 participants. Grade 3 (Severe)/Grade 4 (Very Severe)AEs per World Health Organization (WHO) criteria.Serious adverse events/deaths reported for enrolled patients regardless of treatment status.
Time frame: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Population: Treated cohort: includes participants who are randomized and received at least 1 dose of study drug (ETV or LVD).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Deaths | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | SAEs | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Discontinuations Due to AEs | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Any AEs | 14 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Most common AEs: Upper Respiratory Infection | 3 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Most common AEs: Nasopharyngitis | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Most common AEs: Urticaria | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | WHO Grade 3/4 AEs | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | WHO Grade 3/4 AEs | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Deaths | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Most common AEs: Upper Respiratory Infection | 7 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | SAEs | 3 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Most common AEs: Urticaria | 3 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Discontinuations Due to AEs | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Most common AEs: Nasopharyngitis | 4 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24 | Any AEs | 23 Participants |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
Population: Participants who were randomized and received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Discontinuations due to AEs | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Nonserious AEs related to study conditions | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Any nonserious AEs | 48 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | SAEs related to study conditions | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | SAEs | 7 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | SAEs related to study conditions | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | SAEs | 17 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Discontinuations due to AEs | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Any nonserious AEs | 49 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240 | Nonserious AEs related to study conditions | 6 Participants |
Secondary
Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24
ALT flares=ALT\>2\*Baseline and 10\*upper limit of normal. Serious adverse events/deaths reported for enrolled patients regardless of treatment status.
Time frame: Start of dosing (Day 1) until end of treatment (24 weeks) + 5 days and to end of 24-week follow-up period
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | AST elevations >2*BL | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | Simultaneous ALT & Total bilirubin elevation | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | ALT elevations >3*BL & AST elevations >2*BL | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | ALT flares | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | ALT elevations >2*Baseline (BL) | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | ALT flares | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | ALT elevations >2*Baseline (BL) | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | AST elevations >2*BL | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | ALT elevations >3*BL & AST elevations >2*BL | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24 | Simultaneous ALT & Total bilirubin elevation | 0 Participants |
Secondary
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
ULN=upper limit of normal; ALT=alanine transaminase. WHO criteria: Grade 3=Severe (inability to carry out usual activity); Grade 4=Very severe (debilitating or significantly incapacitating patient despite symptomatic treatment).
Time frame: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to the end of the 24-week follow-up period
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 4 Prothrombin time (>3*ULN) | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 3 Glucose (251-500 mg/dL) | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 3 ALT (5.1-10*ULN) | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 3 Lipase (2.0-5.0*ULN) | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 3 Lipase (2.0-5.0*ULN) | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 4 Prothrombin time (>3*ULN) | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 3 ALT (5.1-10*ULN) | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 | Gr 3 Glucose (251-500 mg/dL) | 2 Participants |
Secondary
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
ULN=upper limit of normal; ALT=alanine transaminase. WHO criteria: Grade 3=Severe (inability to carry out usual activity); Grade 4=Very severe (debilitating or significantly incapacitating patient despite symptomatic treatment).
Time frame: Start of dosing (Day 1) until Week 96
Population: Randomized participants who received at least 1 dose of study drug and who were evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Neutrophils | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Total bilirubiin | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Prothrombin time | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Creatinine | 2 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | AST | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Lipase | 2 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Platelets | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Potassium | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | ALT | 0 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Glucose, fasting | 3 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Glucose, fasting | 2 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Platelets | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Prothrombin time | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Neutrophils | 1 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | AST | 3 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | ALT | 6 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Total bilirubiin | 3 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Creatinine | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Lipase | 4 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 | Potassium | 1 Participants |
Secondary
Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96
The number and percentage of participants achieving the following endpoints will be tabulated at each visit through Week 240 by treatment group: HBV DNA \<300 copies/mL by PCR assay; HBV DNA \<10\^3, \<10\^4, or \< 10\^5 copies/mL by PCR assay. Treatment comparisons will be assessed using the same method as the primary endpoint.
Time frame: At Weeks 24, 48, and 96
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 24: HBV DNA <10^4 | 54 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 48: HBV DNA <10^5 | 55 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 48: HBV DNA <10^3 | 54 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 96: HBV DNA <10^3 | 53 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 24: HBV DNA <10^5 | 54 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 96: HBV DNA <10^4 | 53 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 48: HBV DNA <10^4 | 55 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 96: HBV DNA <10^5 | 53 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 24: HBV DNA <10^3 | 54 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 96: HBV DNA <10^5 | 45 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 24: HBV DNA <10^3 | 46 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 24: HBV DNA <10^4 | 53 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 24: HBV DNA <10^5 | 59 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 48: HBV DNA <10^3 | 45 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 48: HBV DNA <10^4 | 50 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 48: HBV DNA <10^5 | 52 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 96: HBV DNA <10^3 | 38 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96 | Week 96: HBV DNA <10^4 | 42 Participants |
Comparison: HBV DNA \<10\^3 copies/mL at 24 Weeksp-value: 0.000390% CI: [14.45, 34.66]Chi-squared
Comparison: HBV DNA \<10\^4 copies/mL at 24 Weeksp-value: 0.016790% CI: [4.85, 22.38]Chi-squared
Comparison: HBV DNA \<10\^5 at 24 Weeksp-value: 0.446790% CI: [-2.62, 11.1]Chi-squared
Comparison: HBV DNA \<10\^3 copies/mL at 48 Weeksp-value: 0.000290% CI: [15.87, 36.36]Chi-squared
Comparison: HBV DNA \<10\^4 copies/mL at 48 Weeksp-value: 0.000990% CI: [11.1, 29.07]Chi-squared
Comparison: HBV DNA \<10\^5 at 48 Weeksp-value: 0.002990% CI: [8.43, 25.5]Chi-squared
Comparison: HBV DNA \<10\^3 copies/mL at 96 Weeksp-value: <0.000190% CI: [24.02, 46.51]Chi-squared
Comparison: HBV DNA \<10\^4 copies/mL at 96 Weeksp-value: <0.000190% CI: [18.07, 39.97]Chi-squared
Comparison: HBV DNA \<10\^5 copies/mL at 96 Weeksp-value: 0.000690% CI: [13.71, 34.95]Chi-squared
Secondary
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
Normalization of serum ALT= ≤\*institutional upper limit of normal.
Time frame: At Weeks 24, 48, and 96
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At 24 Weeks | 43 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At 48 Weeks | 48 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At 96 Weeks | 49 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At 24 Weeks | 37 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At 96 Weeks | 33 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96 | At 48 Weeks | 38 Participants |
p-value: 0.027890% CI: [5.22, 32.73]Chi-squared
p-value: 0.001490% CI: [13.65, 39.03]Chi-squared
p-value: <0.000190% CI: [23.35, 48.52]Chi-squared
Secondary
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96
Virologic rebound was defined as a confirmed ≥1 log10 increase in HBV DNA from nadir on blinded treatment (as determined by 2 sequential HBV DNA values or last on-treatment measurement).
Time frame: At 96 weeks
Population: All participants who received study drug and who had samples of measureable HBV DNA values
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 | Viral rebound | 1 Participants |
| Entecavir, 0.5 mg + Placebo | Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 | Drug-resistant mutations | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 | Viral rebound | 26 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 | Drug-resistant mutations | 13 Participants |
Comparison: Viral rebound at 96 weeksp-value: <0.0001Chi-squared
Secondary
Number of Participants With Virologic Rebound at Week 24
Virologic rebound was defined as a confirmed ≥1 log10 increase in hepatitis B virus (HBV) DNA from nadir on blinded treatment (as determined by 2 sequential HBV DNA measurements or last on-treatment measurement).
Time frame: At Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir, 0.5 mg + Placebo | Number of Participants With Virologic Rebound at Week 24 | 0 Participants |
| Lamivudine, 100 mg + Placebo | Number of Participants With Virologic Rebound at Week 24 | 3 Participants |
Secondary
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
Undetectable HBV DNA= \<300 copies/mL by polymerase chain reaction assay
Time frame: At Weeks 48, 96, 144, 192, and 240
Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir, 0.5 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 96 Weeks | 94.64 Percetage of participants |
| Entecavir, 0.5 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 192 Weeks | 69.64 Percetage of participants |
| Entecavir, 0.5 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 144 Weeks | 67.86 Percetage of participants |
| Entecavir, 0.5 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 240 Weeks | 67.86 Percetage of participants |
| Entecavir, 0.5 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 48 Weeks | 94.64 Percetage of participants |
| Lamivudine, 100 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 240 Weeks | 15.63 Percetage of participants |
| Lamivudine, 100 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 48 Weeks | 60.94 Percetage of participants |
| Lamivudine, 100 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 96 Weeks | 48.44 Percetage of participants |
| Lamivudine, 100 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 144 Weeks | 34.38 Percetage of participants |
| Lamivudine, 100 mg + Placebo | Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 | At 192 Weeks | 25.00 Percetage of participants |
p-value: <0.000190% CI: [22.52, 44.89]Chi-squared
p-value: <0.000190% CI: [34.8, 57.61]Chi-squared
p-value: 0.000390% CI: [19.31, 47.65]Chi-squared
p-value: <0.000190% CI: [31.17, 58.11]Chi-squared
p-value: <0.000190% CI: [39.54, 64.93]Chi-squared