Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials

A Preliminary Assessment of Safety and Antiviral Activity of Open-label Entecavir in Subjects With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01438424

Enrollment

1053

Registered

2011-09-22

Start date

2001-01-31

Completion date

2011-04-30

Last updated

2012-08-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HBV, Hepatitis B Virus

Brief summary

The purpose of this study is to provide entecavir to participants who have completed another entecavir trial without achieving virologic response or who relapsed during postdosing follow-up.

Interventions

DRUGEntecavir

Tablets, Oral, 1.0 mg, once daily

DRUGLamivudine

Oral, 100 mg, daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

16 Years to No maximum

Healthy volunteers

Inclusion criteria

Key inclusion criteria: * Age of 16 years and older * Receipt of entecavir or lamivudine in a previous entecavir study. Participants who were, based on their response to entecavir: * Virologic nonresponders at Week 48 * Partial virologic responders who became nonresponders during the second year of treatment * Partial virologic responders at Week 96 * Complete responders who relapsed during postdosing follow-up * Decompensated liver disease in AI463-048 that met 1 or more of the following criteria: * Nonresponse to adefovir after at least 24 weeks of treatment * Partial response to adefovir after 96 weeks of treatment * Complete response to adefovir after relapsing during postdosing follow-up * Demonstrated intolerance to adefovir * Except for those participants enrolled from AI463-048, compensated liver disease. Key

Exclusion criteria

* HIV coinfection * Receiving nephrotoxic or hepatotoxic agents * Ongoing opportunistic infections * Hemoglobin level \<11.0 g/dL except for those enrolled from AI463-048 * Platelet count \<70,000 mm\^3 except for those enrolled from AI463-048 * Absolute granulocyte count \<1,500 cells/mm\^3 * Recent history of pancreatitis (within 24 weeks prior to first dose of therapy) * Current evidence of ascites requiring paracentesis, hepatic encephalopathy, or variceal bleeding, except for those enrolled from AI463-048 * Known history of allergy to nucleoside analogues.

Design outcomes

Primary

Measure	Time frame	Description
Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Continuously from Day 1 through Week 240	An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment. An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine transaminase; ULN=upper limit of normal.
Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Day 1 of treatment through Week 240	Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0; Gr 2=8.0-\<9.5; Gr 3=6.5-\<8.0; Gr 4=\<6.5 White blood cells (cells/mm\^3): Gr 1=2,500-\<4,000; Gr 2=1,000-\<2,500; Gr 3=800-\<1,000; Gr 4=\<800. Neutrophils (cells/mm\^3): Gr 1=1000-\<1500; Gr 2=750-\<1000; Gr 3=500-\<750; Gr 4=\<500. Platelets (cells/mm\^3): Gr 1=75,000-99,000; Gr 2=50,000-\<75,000; Gr 3=20,000-\<50,000; Gr 4=\<20,000. Prothrombin time (seconds): Gr 1=1.01-\<1.26\ULN; Gr 2=1.26-\<1.51 \ULN; Gr 3=1.51-3\ULN; Gr 4=\>3\ULN. INR: Gr 1=1.24-1.5; Gr 2=1.5-2; Gr 3=2-3; Gr 4=\>3. INR=international normalized ratio; ULN=upper limit of normal. .
Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Day 1 of treatment through Week 240	Amylase: Grade 1=1.10-\<1.40\ULN; Grade 2=1.40-\< 2.10\ULN; Grade 3=2.10-5.00\ULN; Grade 4=\>5.00\ULN. Lipase: Grade 1.1-\<1.4\ULN; Grade 2=1.4-\<2.1\ULN; Grade 3=2.1-5.0\ULN; Grade 4=\>5.0\ULN. Creatinine: Grade 1=1.10-\< 1.60\ULN; Grade 2=1.60-\<3.10\ULN; Grade 3=3.10-6.00\ULN; Grade 4=\>6.00\ULN. Blood urea nitrogen (BUN): Grade 1=1.25-\<2.60\ULN; Grade 2=2.60-\<5.10\ULN; Grade 3=5.10-10\ULN; Grade 4=\>10\ULN. ULN=upper limit of normal.
Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Day 1 of treatment through Week 240	Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-\<90; Gr 3=80-\<85; Gr 4=40-\<80. Hyperchloremia: Gr 1=113-\<117; Gr 2=117-\<121; Gr 3=121-125; Gr 4\>125. Hypocarbia: Gr 1=19-21; Gr 2=15-\<19; Gr 3=41-45; Gr 4=\>45. Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=\>45. Hyponatremia: Gr 1=130-132; Gr 2=123-\<130; Gr 3=116-\<123; Gr 4\<116. Hypernatremia: Gr 1=148-\<151; Gr 2=151-\<158; Gr 3=158-165; Gr 4=\>165. Hypokalemia: Gr 1=3-3.4; Gr 2=2.5-\<3; Gr 3=2-\<2.5; Gr 4=\<2. Hyperkalemia: Gr 1=5.6-\<6.1; G2=6.1-\<6.6; Gr 3=6.6-7; Gr 4=\>7. Hypoglycemia: Gr 1=55-64; Gr 2=40-\<55; Gr 3=30-\< 40; G4=-\<30. Hyperglycemia: Gr 1=116-\<161; Gr 2=161-\<251; Gr 3=251-500; Gr 4\>500.
Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Continuously from Day 1 through Week 144	An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. AST=aspartate aminotransferase; ULN=upper limit of normal.
Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Continuously from Day 1 through Week 192	An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine aminotransferase; ULN=upper limit of normal.
Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)	End of dosing to Week 48 off-treatment follow-up	The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.

Secondary

Measure	Time frame	Description
Overall Study: Percentage of Participants Who Achieved ALT Normalization	Study entry to Week 216	ULN=upper limit of normal. ALT normalization=ALT levels ≤1.0\*ULN.
Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)	Baseline to Week 192	The Knodell Histologic Activity Index scores stage of necrosis and grade of inflammation in liver biopsies. Components are necrosis near the portal vein, intralobular degeneration and focal necrosis, portal inflammation, and fibrosis. The 4 components are scored from 1 to 4 and 1 to 10 (necrosis near the portal vein) and combined for a total score, with 22 being the highest possible score. Higher the score for each component=greater liver damage. Histologic improvement=a ≥2-point reduction in total Knodell score and no worsening in fibrosis. Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell necroinflammatory scores ≥2.
Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	End of dosing to Weeks 48 and 96 off-treatment follow-up	The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR Assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing. ULN=upper limit of normal.
Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)	Baseline to Week 192	The Ishak Modification for Hepatic Activity Index (HAI) scores necroinflammatory activity in chronic hepatitis. 0=no fibrosis, 1=fibrosis expansion of some portal areas, 2=fibrosis expansion of most portal areas, 3=fibrosis expansion of most portal areas with occasional bridging, 4=fibrosis expansion of portal areas with marked bridging, 5=incomplete cirrhosis, 6=probable or definite cirrhosis. Higher score=more severe necrosis. Improvement in fibrosis=≥1-point reduction in HAI score. Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell scores ≥2.
Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay	Baseline to Week 144	—
Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Baseline to Weeks 48, 96, 144, 192, and 240	The Entecavir Continuous Treatment Cohort consisted of participants from study AI463-022 (NCT00035633) who were nucleoside-naive HBeAg-positive and enrolled in the current study with ≤35 days off treatment between the last dose in AI463-022 and the first dose in the current. This cohort is considered to be on continuous entecavir treatment and permitted assessment of continuous administration of entecavir in AI463-022 and the current study.
Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay	Study entry to Week 192	—
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	Baseline to Week 96	The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	Baseline to Week 144	The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)	Baseline to Week 96	The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with \>60 days between end of dosing in AI463-027 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)	Baseline to Week 144	The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with \>60 days between end of dosing in AI463-027 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)	End of dosing to Weeks 48 and 96 off-treatment follow-up	The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.
Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Baseline to Weeks 48, 96, and 144	The Entecavir Retreatment Cohort consisted of participants who were nucleoside-naive, HBeAg-negative and enrolled from BMS study AI463-027 with \>60 days off treatment between the last dose in AI463-027 and the first dose in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as retreatment in the current study.
Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay	Study entry to Week 192	—
Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline to Week 192	Observed values.
Overall Study: Mean HBV DNA Level by PCR Assay	Study entry to Week 216	—
Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Study entry to Week 216	Observed values.
Overall Study: Percentage of Participants With HBeAg Seroconversion	Study entry to Week 216	Observed values. Seroconversion=negative HBeAg with detectable anti-HBe antibody.
Overall Study: Mean Alanine Transaminase (ALT) Levels	Study entry to Week 216	Observed values.

Participant flow

Pre-assignment details

Of 1053 participants enrolled, 1051 received treatment.

Participants by arm

Arm	Count
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine Participants originally received 0.5 mg of entecavir once daily (QD) with lamivudine, but protocol later amended to 1.0 mg of entecavir QD without lamivudine.	1,051
Total	1,051

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Abnormal laboratory test result	14
Overall Study	Adverse Event	17
Overall Study	Continuing treatment	29
Overall Study	Death	22
Overall Study	Lost to Follow-up	17
Overall Study	Minimal virologic response	95
Overall Study	Need for drug prohibited by protocol	14
Overall Study	No longer met inclusion criteria	1
Overall Study	Not identified	55
Overall Study	Participant noncompliance	20
Overall Study	Pregnancy	7
Overall Study	Progression of chronic hepatitis B	22
Overall Study	Withdrawal by Subject	104

Baseline characteristics

Characteristic	Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine
Age	41 Years
Age, Customized	41 Years STANDARD_DEVIATION 13
Race/Ethnicity, Customized Asian/Pacific Islander	544 Participants
Race/Ethnicity, Customized Black/African American	18 Participants
Race/Ethnicity, Customized Filipino	1 Participants
Race/Ethnicity, Customized Hispanic/Latino	1 Participants
Race/Ethnicity, Customized Missing	2 Participants
Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander	2 Participants
Race/Ethnicity, Customized Other	2 Participants
Race/Ethnicity, Customized White	481 Participants
Region: Continent Asia	451 Participants
Region: Continent Europe	334 Participants
Region: Continent North America	141 Participants
Region: Continent South America	125 Participants
Sex: Female, Male Female	241 Participants
Sex: Female, Male Male	810 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	27 / 35	0 / 1	25 / 29	274 / 336	94 / 123	439 / 523	2 / 2	1 / 2
serious Total, serious adverse events	7 / 35	0 / 1	3 / 29	57 / 336	15 / 123	87 / 523	0 / 2	0 / 2

Outcome results

Primary

Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)

The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.

Time frame: End of dosing to Week 48 off-treatment follow-up

Population: Participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)	End of dosing current study	100 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)	Off-treatment Week 48	21 Percentage of participants

Primary

Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs

An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment. An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine transaminase; ULN=upper limit of normal.

Time frame: Continuously from Day 1 through Week 240

Population: All participants who received at least 1 dose of study drug in the current study.

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Discontinuations due to AEs on treatment	14 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Any AE on treatment	900 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Grade 3 and 4 AEs on treatment	203 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Malignancies on and off treatment	35 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	ALT flares (ALT>2entry and >10ULN) on treatment	32 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Hepatic disease progression on and off treatment	33 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Deaths on treatment	18 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	Deaths off treatment	9 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs	SAEs on treatment	169 Participants

Primary

Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing

Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-\<90; Gr 3=80-\<85; Gr 4=40-\<80. Hyperchloremia: Gr 1=113-\<117; Gr 2=117-\<121; Gr 3=121-125; Gr 4\>125. Hypocarbia: Gr 1=19-21; Gr 2=15-\<19; Gr 3=41-45; Gr 4=\>45. Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=\>45. Hyponatremia: Gr 1=130-132; Gr 2=123-\<130; Gr 3=116-\<123; Gr 4\<116. Hypernatremia: Gr 1=148-\<151; Gr 2=151-\<158; Gr 3=158-165; Gr 4=\>165. Hypokalemia: Gr 1=3-3.4; Gr 2=2.5-\<3; Gr 3=2-\<2.5; Gr 4=\<2. Hyperkalemia: Gr 1=5.6-\<6.1; G2=6.1-\<6.6; Gr 3=6.6-7; Gr 4=\>7. Hypoglycemia: Gr 1=55-64; Gr 2=40-\<55; Gr 3=30-\< 40; G4=-\<30. Hyperglycemia: Gr 1=116-\<161; Gr 2=161-\<251; Gr 3=251-500; Gr 4\>500.

Time frame: Day 1 of treatment through Week 240

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyponatremia (mEq/L) (All grades) (n=1003)	68 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypochloremia (mEq/L) (All grades) (n=982)	44 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyperchloremia (mEq/L) (All grades) (n=982)	76 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypocarbia (mEq/L) (All grades) (n=831)	285 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypercarbia (mEq/L) (All grades) (n=831)	148 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypernatremia (mEq/L) (All grades) (n=1003)	106 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypokalemia (mEq/L) (All grades) (n=993)	135 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyperkalemia (mEq/L) (All grades (n=993)	42 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypochloremia (mEq/L) (Grades 3-4) (n=982)	3 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyperchloremia (mEq/L) (Grades 3-4) (n=982)	7 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypocarbia (mEq/L) (Grades 3-4) (n=831)	14 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypercarbia (mEq/L) (Grades 3-4) (n=831)	2 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyponatremia (mEq/L)(Grades 3-4) (n=1003)	2 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypernatremia (mEq/L) (Grades 3-4) (n=1003)	5 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypokalemia (mEq/L) (Grades 3-4) (n=993)	1 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyperkalemia (mEq/L) (Grades 3-4) (n=993)	6 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypoglycemia (mg/dL) (All grades) (n=521)	47 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyperglycemia (mg/dL) (All grades) (n=521)	150 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hypoglycemia (mg/dL) (Grades 3-4) (n=521)	3 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing	Hyperglycemia (mg/dL) (Grades 3-4) (n=521)	4 Participants

Primary

Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240

Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0; Gr 2=8.0-\<9.5; Gr 3=6.5-\<8.0; Gr 4=\<6.5 White blood cells (cells/mm\^3): Gr 1=2,500-\<4,000; Gr 2=1,000-\<2,500; Gr 3=800-\<1,000; Gr 4=\<800. Neutrophils (cells/mm\^3): Gr 1=1000-\<1500; Gr 2=750-\<1000; Gr 3=500-\<750; Gr 4=\<500. Platelets (cells/mm\^3): Gr 1=75,000-99,000; Gr 2=50,000-\<75,000; Gr 3=20,000-\<50,000; Gr 4=\<20,000. Prothrombin time (seconds): Gr 1=1.01-\<1.26\*ULN; Gr 2=1.26-\<1.51 \*ULN; Gr 3=1.51-3\*ULN; Gr 4=\>3\*ULN. INR: Gr 1=1.24-1.5; Gr 2=1.5-2; Gr 3=2-3; Gr 4=\>3. INR=international normalized ratio; ULN=upper limit of normal. .

Time frame: Day 1 of treatment through Week 240

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Hemoglobin (All grades) (n=1007)	49 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	White blood cells (All grades) (n=950)	226 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Neutrophils (All grades) (n=1002)	109 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	INR (All grades)(n=746)	214 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Hemoglobin (Grades 3-4) (n=1007)	2 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	White blood cells (Grades 3-4) (n=950)	1 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Neutrophils (Grades 3-4) (n=1002)	21 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Platelets (Grades 3-4) (n=979)	1 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Prothrombin time (Grades 3-4) (n=746)	21 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	INR (Grades 3-4) (n=746)	12 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Platelets (All grades) (n=979)	51 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240	Protrombin time (All grades) (n=746)	226 Participants

Primary

Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing

Amylase: Grade 1=1.10-\<1.40\*ULN; Grade 2=1.40-\< 2.10\*ULN; Grade 3=2.10-5.00\*ULN; Grade 4=\>5.00\*ULN. Lipase: Grade 1.1-\<1.4\*ULN; Grade 2=1.4-\<2.1\*ULN; Grade 3=2.1-5.0\*ULN; Grade 4=\>5.0\*ULN. Creatinine: Grade 1=1.10-\< 1.60\*ULN; Grade 2=1.60-\<3.10\*ULN; Grade 3=3.10-6.00\*ULN; Grade 4=\>6.00\*ULN. Blood urea nitrogen (BUN): Grade 1=1.25-\<2.60\*ULN; Grade 2=2.60-\<5.10\*ULN; Grade 3=5.10-10\*ULN; Grade 4=\>10\*ULN. ULN=upper limit of normal.

Time frame: Day 1 of treatment through Week 240

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Amylase (All grades) (n=875)	179 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Amylase (Grades 3-4) (n=875)	13 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Lipase (Grades 3-4) (n=390)	38 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	BUN/Urea (All grades) (n=998)	57 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Creatinine (All grades) (n=1000)	61 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	BUN/Urea (Grades 3-4) (n=998)	0 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Lipase (All grades) (n=390)	126 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing	Creatinine (Grades 3-4) (n=1000)	2 Participants

Primary

Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. AST=aspartate aminotransferase; ULN=upper limit of normal.

Time frame: Continuously from Day 1 through Week 144

Population: Participants enrolled up to Week 144 who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Malignant neoplasms	17 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	SAEs	107 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Discontinuations due to AEs	13 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	ALT >5.0*ULN	93 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Lipase >2.0*ULN	71 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Deaths on study	13 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Any AE	842 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Grade 3 and 4 AEs	156 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	ALT flares (ALT>2entry and >10ULN)	29 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	AST >5.0*ULN	53 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Total bilirubin >2.5*ULN	22 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Creatinine ≥0.5 mg/dL from baseline	6 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Hypocarbia	4 Participants

Primary

Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine aminotransferase; ULN=upper limit of normal.

Time frame: Continuously from Day 1 through Week 192

Population: Participants who enrolled from Phase 3 studies of nucleoside-naive HBeAg-positive (AI463-022) and HBeAg-negative (AI463-027) participants and received at least 1 dose of study drug in the current study up to Week 192. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Deaths on study	18 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Malignant neoplasms	27 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	SAEs	135 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Discontinuations due to AEs	11 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Any AE	862 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Grade 3 and 4 AEs	174 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	ALT flares (ALT>2entry and >10ULN)	30 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	ALT >5.0*ULN	175 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Total bilirubin >2.5*ULN	32 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Lipase >2.0*ULN	81 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Creatinine ≥0.3 mg/dL from baseline	80 Participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results	Hypocarbia Grades 3-4	5 Participants

Secondary

Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)

The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.

Time frame: End of dosing to Weeks 48 and 96 off-treatment follow-up

Population: Participants who were HBeAg negative and who had liver disease, a minimum of 192 weeks of entecavir treatment, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks before end of dosing, and had serum ALT levels ≤1.0\*ULN at the end of study drug dosing. (n=number of evaluable participants)

Arm	Measure	Group	Value (MEAN)	Dispersion
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)	Off-treatment Week 48	1.54 Log10 copies/mL	Standard Error 0.336
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)	Off-treatment Week 96	1.18 Log10 copies/mL	Standard Error 0.326

Secondary

Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)

The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR Assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing. ULN=upper limit of normal.

Time frame: End of dosing to Weeks 48 and 96 off-treatment follow-up

Population: Participants who were HBeAg negative and who had liver disease, a minimum of 192 weeks of entecavir treatment, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks before end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off-treatment Week 48 <1000 copies/mL	10 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off-treatment Week 96 <1000 copies/mL	10 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off-treatment Week 48 <300 copies/mL	7 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off-treatment Week 96 <300 copies/mL	3 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off treatment Week 96 <10,000 copies/mL	14 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off treatment Week 48: ALT ≤1*ULN	31 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)	Off treatment Week 96: ALT ≤1*ULN	24 Percentage of participants

Secondary

Overall Study: Mean Alanine Transaminase (ALT) Levels

Observed values.

Time frame: Study entry to Week 216

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (MEAN)	Dispersion
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	At study entry (n=1051)	109.4 U/L	Standard Deviation 170.5
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 12 (n=1049)	48.77 U/L	Standard Deviation 48.68
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 24 (n=1029)	42.10 U/L	Standard Deviation 36.83
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 48 (n=942)	37.06 U/L	Standard Deviation 34.2
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 72 (n=835)	38.10 U/L	Standard Deviation 41.9
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 96 (n=740)	39.30 U/L	Standard Deviation 46.35
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 120 (n=675)	37.43 U/L	Standard Deviation 28.97
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 144 (n=627)	38.51 U/L	Standard Deviation 38.95
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 168 (n=563)	36.80 U/L	Standard Deviation 29.06
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 192 (n=528)	37.36 U/L	Standard Deviation 30.44
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean Alanine Transaminase (ALT) Levels	Week 216 (n=482)	38.43 U/L	Standard Deviation 55.09

Secondary

Overall Study: Mean HBV DNA Level by PCR Assay

Time frame: Study entry to Week 216

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (MEAN)	Dispersion
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	At study entry (n=1051)	6.14 log10 copies/mL	Standard Deviation 2.667
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 12 (n=1017)	3.87 log10 copies/mL	Standard Deviation 1.749
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 24 (n=1010)	3.62 log10 copies/mL	Standard Deviation 1.684
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 48 (n=905)	3.37 log10 copies/mL	Standard Deviation 1.543
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 72 (n=769)	3.31 log10 copies/mL	Standard Deviation 1.549
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 96 (n=691)	3.34 log10 copies/mL	Standard Deviation 1.592
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 120 (n=629)	3.32 log10 copies/mL	Standard Deviation 1.665
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 144 (n=597)	3.34 log10 copies/mL	Standard Deviation 1.826
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 168 (n=514)	3.18 log10 copies/mL	Standard Deviation 1.663
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 192 (n=485)	3.19 log10 copies/mL	Standard Deviation 1.757
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Mean HBV DNA Level by PCR Assay	Week 216 (n=455)	3.20 log10 copies/mL	Standard Deviation 1.789

Secondary

Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay

Observed values.

Time frame: Baseline to Week 192

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)	Dispersion
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: <300 copies/mL (n=1051)	17 Percentage of participants	4
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 300 - <1.0E3 copies/mL (n=1051)	4 Percentage of participants	8
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E3 - <1.0E4 copies/mL (n=1051)	8 Percentage of participants	13
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E4 - <1.0E5 copies/mL (n=1051)	8 Percentage of participants	11
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E5 - <1.0E6 copies/mL (n=1051)	12 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E6 - <1.0E7 copies/mL (n=1051)	13 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E7 - <1.0E8 copies/mL (n=1051)	8 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E8 - <1.0E9 copies/mL (n=1051)	11 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: 1.0E9 - <1.0E10 copies/mL (n=1051)	13 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Baseline: >= 1.0E10 copies/mL (n=1051)	6 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: < 300 copies/mL (n=485)	78 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 300 - <1.0E3 copies/mL (n=485)	3 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E3 - <1.0E4 copies/mL (n=485)	3 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E4 - <1.0E5 copies/mL (n=485)	4 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E5 - <1.0E6 copies/mL (n=485)	2 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E6 - <1.0E7 copies/mL (n=485)	2 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E7 - <1.0E8 copies/mL (n=485)	1 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E8 - <1.0E9 copies/mL (n=485)	5 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: 1.0E9 - <1.0E10 copies/mL (n=485)	2 Percentage of participants	—
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay	Week 192: >= 1.0E10 copies/mL (n=485)	0 Percentage of participants	—

Secondary

Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)

Observed values.

Time frame: Study entry to Week 216

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	At study entry (n=1051)	34 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 12 (n=935)	40 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 24 (n=939)	42 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 48 (n=864)	46 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 72 (n=752)	45 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 96 (n=679)	50 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 120 (n=609)	51 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 144 (n=587)	53 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 168 (n=518)	58 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 192 (n=491)	60 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)	Week 216 (n=436)	59 Percentage of participants

Secondary

Overall Study: Percentage of Participants Who Achieved ALT Normalization

ULN=upper limit of normal. ALT normalization=ALT levels ≤1.0\*ULN.

Time frame: Study entry to Week 216

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved ALT Normalization	At study entry (n=1019)	40 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved ALT Normalization	Week 48 (n=942)	75 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved ALT Normalization	Week 144 (n=627)	74 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants Who Achieved ALT Normalization	Week 216 (n=482)	78 Percentage of participants

Secondary

Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay

Time frame: Baseline to Week 144

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay	18 Percentage of participants

Secondary

Overall Study: Percentage of Participants With HBeAg Seroconversion

Observed values. Seroconversion=negative HBeAg with detectable anti-HBe antibody.

Time frame: Study entry to Week 216

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 216 (n=434)	40 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	At study entry (n=1051)	30 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 12 (n=931)	33 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 24 (n=934)	34 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 48 (n=862)	36 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 72 (n=755)	32 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 96 (n=678)	34 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 120 (n=607)	36 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 144 (n=587)	37 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 168 (n=517)	39 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With HBeAg Seroconversion	Week 192 (n=491)	42 Percentage of participants

Secondary

Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay

Time frame: Study entry to Week 192

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay	At study entry (n=1051)	28 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay	Week 48 (n=905)	76 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay	Week 96 (n=691)	77 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay	Week 144 (n=597)	81 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay	Week 192 (n=485)	85 Percentage of participants

Secondary

Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay

Time frame: Study entry to Week 192

Population: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay	At study entry (n=1051)	17 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay	Week 48 (n=905)	63 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay	Week 96 (n=691)	67 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay	Week 144 (n=597)	73 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay	Week 192 (n=485)	78 Percentage of participants

Secondary

Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)

The Entecavir Retreatment Cohort consisted of participants who were nucleoside-naive, HBeAg-negative and enrolled from BMS study AI463-027 with \>60 days off treatment between the last dose in AI463-027 and the first dose in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as retreatment in the current study.

Time frame: Baseline to Weeks 48, 96, and 144

Population: Participants enrolled from study AI463-027 who were nucleoside-naive, HBeAg-negative and had \>60 days off treatment between the last dose in AI463-027 and the first dose in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week 48: HBV DNA <300 copies/mL (n=119)	88 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week 48: HBV DNA <10^4 copies/mL (n=88)	87 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week: 48: ALT ≤1.0*ULN (n=95)	83 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week 96: HBV DNA <300 copies/mL (n=74)	91 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week: 96: ALT ≤1.0*ULN (n=76)	79 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week 144: HBV DNA <300 copies/mL (n=57)	95 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)	Week 144: ALT ≤1.0*ULN (n=66)	86 Percentage of participants

Secondary

Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)

The Entecavir Continuous Treatment Cohort consisted of participants from study AI463-022 (NCT00035633) who were nucleoside-naive HBeAg-positive and enrolled in the current study with ≤35 days off treatment between the last dose in AI463-022 and the first dose in the current. This cohort is considered to be on continuous entecavir treatment and permitted assessment of continuous administration of entecavir in AI463-022 and the current study.

Time frame: Baseline to Weeks 48, 96, 144, 192, and 240

Population: Participants enrolled from study AI463-022 who were nucleoside-naive, HBeAg-positive and enrolled in the current study with ≤35 days off treatment between the last dose in AI463-022 and the first dose in the current study and were evaluable. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 48: HBV DNA <300 copies/mL (n=146)	55 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 240: ALT ≤1.0*ULN (n=98)	80 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 96: HBV DNA <300 copies/mL (n=140)	83 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 144: HBV DNA <10^4 copies/mL (n=131)	89 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 192: HBV DNA < 10^4 copies/mL (n=108)	91 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 240: HBV DNA <300 copies/mL (n=94)	94 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 48: Loss of HBeAg (n=146)	1 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 96: Loss of HBeAg (n=140)	4 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 144: Loss of HBeAg (n=132)	30 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 192: Loss of HBeAg (n=111)	39 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 240: Loss of HBeAg (n=95)	41 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 48: Seroconversion (n=146)	1 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 96: Seroconversion (n=140)	3 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 144: Seroconversion (n=133)	17 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 192: Seroconversion (n=111)	16 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 240: Seroconversion (n=95)	17 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 48: ALT ≤1.0*ULN (n=146)	65 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 96: ALT ≤1.0*ULN (n=140)	78 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 144: ALT ≤1.0*ULN (n=134)	77 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)	Week 192: ALT ≤1.0*ULN (n=112)	86 Percentage of participants

Secondary

Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)

The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.

Time frame: Baseline to Week 144

Population: Participants enrolled from AI463-022 who received lamivudine, were nucleoside-naive HBeAg-positive, and had ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	HBV DNA <300 copies/mL (n=130)	65 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	Achieved ALT ≤1.0*ULN (n=135)	68 Percentage of participants

Secondary

Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)

The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with \>60 days between end of dosing in AI463-027 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.

Time frame: Baseline to Week 144

Population: Participants enrolled from study AI463-027 who were nucleoside-naive HBeAg-negative and had \>60 days off treatment between the last dose in AI463-027 and the first dose in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)	HBV DNA <300 copies/mL (n=67)	99 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)	Achieved ALT ≤1.0*ULN (n=73)	85 Percentage of participants

Secondary

Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)

The Knodell Histologic Activity Index scores stage of necrosis and grade of inflammation in liver biopsies. Components are necrosis near the portal vein, intralobular degeneration and focal necrosis, portal inflammation, and fibrosis. The 4 components are scored from 1 to 4 and 1 to 10 (necrosis near the portal vein) and combined for a total score, with 22 being the highest possible score. Higher the score for each component=greater liver damage. Histologic improvement=a ≥2-point reduction in total Knodell score and no worsening in fibrosis. Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell necroinflammatory scores ≥2.

Time frame: Baseline to Week 192

Population: Subset of participants who who had evaluable paired liver biopsy results at Phase 3 study baseline and on their last observed biopsies performed in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)	Histologic improvement (n=56) (Week 48)	73 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)	Histologic improvement (n=57) (Long-term biopsy)	96 Percentage of participants

Secondary

Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)

The Ishak Modification for Hepatic Activity Index (HAI) scores necroinflammatory activity in chronic hepatitis. 0=no fibrosis, 1=fibrosis expansion of some portal areas, 2=fibrosis expansion of most portal areas, 3=fibrosis expansion of most portal areas with occasional bridging, 4=fibrosis expansion of portal areas with marked bridging, 5=incomplete cirrhosis, 6=probable or definite cirrhosis. Higher score=more severe necrosis. Improvement in fibrosis=≥1-point reduction in HAI score. Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell scores ≥2.

Time frame: Baseline to Week 192

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)	Improvement in fibrosis (n=57) (Long-term biopsy)	88 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)	Improvement in fibrosis (n=56) (Week 48)	32 Percentage of participants

Secondary

Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)

Time frame: Baseline to Week 96

Population: Participants enrolled from AI463-027 who were nucleoside-naive HBeAg-negative, received lamivudine, and had \>60 days between end of dosing in AI463-027 and the switch to entecavir in the current study. (n=number of evaluable participants)

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)	HBV DNA <300 copies/mL (n=69)	97 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)	ALT ≤1.0*ULN (n=81)	81 Percentage of participants

Secondary

Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)

Time frame: Baseline to Week 96

Arm	Measure	Group	Value (NUMBER)
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	HBV DNA <300 copies/mL (n=147)	58 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	Achieved loss of HbeAg (n=129)	25 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	Achieved HBeAg seroconversion (n=129)	8 Percentage of participants
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)	Achieved ALT ≤1.0*ULN (n=154)	76 Percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)

Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs

Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing

Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240

Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing

Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results

Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results

Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)

Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)

Overall Study: Mean Alanine Transaminase (ALT) Levels

Overall Study: Mean HBV DNA Level by PCR Assay

Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay

Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)

Overall Study: Percentage of Participants Who Achieved ALT Normalization

Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay

Overall Study: Percentage of Participants With HBeAg Seroconversion

Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay

Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay

Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)

Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)

Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)

Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)

Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)

Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)

Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)

Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)