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A Study of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus (HBV)-Infection

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00423891
Collaborator
(none)
64
Enrollment
19
Locations
1
Arm
122.2
Actual Duration (Months)
3.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this clinical study is to determine the appropriate doses of entecavir to use in children and adolescents. Safety, tolerability and efficacy will also be studied

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
64 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Evaluation of the Pharmacokinetics, Safety, Tolerability and Efficacy of Entecavir (ETV) in Pediatric Subjects With Chronic Hepatitis B Virus (HBV) Infection Who Are HBeAg-Positive
Actual Study Start Date :
Jun 30, 2007
Actual Primary Completion Date :
Aug 31, 2013
Actual Study Completion Date :
Sep 4, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: Entecavir

Drug: Entecavir
Tablets / Oral Solution, Oral, Naïve: 0.015 mg/kg up to 0.5 mg; Experienced: 0.030 mg/kg up to 1 mg, once daily, 48 - 120 weeks depending on response
Other Names:
  • Baraclude
  • BMS-200475

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment [Day 1 to Week 120]

      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. Medical Dictionary for Regulatory Activities (MedDRA) version 16.0 was used.

    Secondary Outcome Measures

    1. Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort [Day 14]

      Cmax and Cmin were derived from plasma concentration of ETV versus time and measured in nanograms per milliliters (ng/mL). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. Note: PK parameters were summarized for only Groups A and B. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.

    2. Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort [Day 14]

      Tmax was derived from plasma concentration of ETV versus time and measured in hours (h). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. Age categories presented below: participants age as of first day of dosing. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.

    3. Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort [Day 14]

      Area under the Curve (AUC) was derived from plasma concentration of ETV versus time. AUC(TAU) was calculated by log- and linear trapezoidal summations, TAU = 24 hours, and was measured in nanograms*hours per milliliter (ng*h/mL). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.

    4. Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort [At 2 weeks]

      CLT/F was calculated by dividing the dose of ETV by AUC(TAU) of ETV and was measured in liters per hour (L/h). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.

    5. Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants [Baseline to Week 96]

      Hepatitis B virus DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS TaqMan - high pure system (HPS) assay and was reported in international units per milliliter (IU/mL). Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    6. Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants [Baseline to Week 96]

      HBeAg loss: HBeAg negative. The method used for the detection of HBe Ag was the DiaSorin - Anti HBe enzyme immunoassay kit. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    7. Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants [Baseline to Week 96]

      HBsAg loss: HBsAg negative. The method used for detection of HBsAg was the ADVIA Centaur iImmunoassay system. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    8. Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants [Baseline through Week 96]

      HBe seroconversion: loss of HBeAg (HBeAg negative) with positive HB e antibodies (HBeAb), ie both the presence of HBeAb and the absence of HBeAg. The method used for the detection HBeAg seroconversion was the DiaSorin - Anti HBe enzyme immunoassay kit. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    9. Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants [Baseline to Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLD = 6 IU/mL). Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    10. Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants [Baseline through Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLQ = 29 IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    11. Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants [Baseline through Week 96]

      HB s Ag seroconversion: loss of HBsAg (HBsAg negative) and presence of HB s antibodies (HBsAb). The method used for the detection of HBsAg seroconversion was the ADVIA Centaur iImmunoassay system. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    12. Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants [Baseline to Week 96]

      PDR was defined as confirmed HBV DNA < 50 IU/mL plus confirmed HBeAg seroconversion on 2 sequential measurements at least 14 days apart. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    13. Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants [Baseline to Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. HBV DNA log10 changes from baseline were summarized over time.

    14. Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants [Baseline to Week 96]

      Normalization in ALT= ALT ≤ 1.0*upper limit of normal (ULN). Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    15. Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants [Baseline, Week 48, Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLQ = 29 IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy.

    16. Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants [Baseline to Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0*ULN.

    17. Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants [Baseline to Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0*ULN. HBe seroconversion was determination of presence of HBeAb and loss of HBeAg. The method used for the detection of HBeAg seroconversion was the DiaSorin - Anti HBe enzyme immunoassay kit.

    18. Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants [Baseline to Week 96]

      Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0*ULN. HBe seroconversion: loss of HBeAg (HBeAg negative) with positive HBeAb. The method used for the detection of HBeAg/Ab serologies was the DiaSorin enzyme immunoassay kit.

    19. Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants [Day 1 to Week 120]

      Toxicity Scale: Division of AIDs (DAIDS) grades Version 1.0. Upper limit of normal (ULN); lower limit of normal (LLN); Cells per Liter (c/L); cells per microliter (c/µL); grams per deciliter (g/dL); milliequivalents per liter (mEq/L); cells per microliter (c/µL): Grade (Gr). Hemoglobin g/dL: Gr1:10.0-10.9;Gr2: 9.0-9.9; Gr3:7.0-8.9; Gr4: <7.0. International normalization ratio (INR): Gr1:1.1-<1.5*ULN; Gr2: 1.6-<2.0*ULN; Gr3: 2.1-3.0*ULN;Gr4: >3.0*ULN. Neutrophils/bands c/µL: Gr1;1.0-1.3*10^3; Gr2: 0.75-0.99*10^3; Gr 3: 0.50-0.749*10^3; Gr4: <0.5*10^3.

    20. Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants [Day 1 to Week 120]

      Toxicity Scale: DAIDS Version 1.0 and modified World Health Organization (WHO). Grade (Gr). ALT: Gr1:1.25-<2.5*ULN; Gr2: 2.6-<5.0 *ULN; Gr3: 5.1-10.0*ULN; Gr4:>10.0*ULN. Aspartate aminotransferase (AST): Gr1: 1.25-<2.5*ULN; Gr2:2.6-<5.0*ULN; Gr 3: 5.1-10.0*ULN; Gr4>10.0*ULN. Alkaline phosphatase: Gr1:1.25-<2.5*ULN; Gr2: 2.6-<5.0*ULN; Gr3: 5.1-10.0*ULN; Gr4: >10.0*ULN. Lipase: Gr1:1.1-<1.5*ULN;Gr2:1.6-<3.0*ULN; Gr3: 3.1-5.0*ULN; Gr4: >5.0*ULN. Creatinine: Gr1: 1.1-1.3*ULN; Gr2: 1.4-<1.8*ULN; Gr3: 1.9 - <3.4*ULN; Gr4: >=3.5*ULN. Glucose mg/dL (high): Gr1:110-<125 (Fasting)/116-<160;Gr2:126-<250 (F)/161-<250; Gr3: 251-500; Gr4: >500.Glucose (low): Gr1: 55-64; Gr2: 40 - <54; Gr3: 30-39; Gr4: <30 mg/dL.

    21. Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants [Day 1 Week 120]

      Toxicity Scale: DAIDS Version 1.0 and modified World Health Organization (WHO) for chloride. Milliequivalents per liter (mEq/L); Grade (Gr). Chloride high (mEq/L): Gr1: 113-<117; Gr2: 117-<121; Gr3: 121-125; Gr4: >125. Potassium low (mEq/L): Gr1: 3.0-3.4; Gr2: 2.5-2.9; Gr3:2.0-<2.4; Gr4: <2.0. Potassium high: Gr1; 5.6- <6.0; Gr2: 6.1-<6.5; Gr3: 6.6-7.0; Gr4: >7.0. Sodium high (mEq/L): Gr1; 146-<150; Gr2: 151-<154; Gr3: 155-<159; Gr4: >=160.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 2-18 years of age

    • Group A: Lamivudine naive (<1 week of Lamivudine) and not within 24 weeks of screening; Group B: Lamivudine experienced (> 12 weeks of Lamivudine); Group C: nucleoside/nucleotide experienced (> 12 weeks of nucleoside/tide therapy) added as a country-specific protocol amendment (not all sites had Group C).

    • HBV Deoxyribonucleic acid (DNA) ≥ 100000 copies/mL; ≥ 10000 copies for nucleoside/nucleotide experienced (Group C)

    • Detectable Hepatitis B surface antigen (HBsAg) for 24 weeks prior to screening

    • Hepatitis B e antigen (HBeAg) positive

    • Compensated liver and renal function

    • Elevated alanine aminotransferase (ALT) at screening and during the 24 weeks prior to screening (for Groups A and B)

    Exclusion Criteria:

    • Coinfection with Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis D Virus (HDV)

    • Children who were breastfed while their mother received Lamivudine, or children whose mothers received Lamivudine during pregnancy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, San Francisco San Francisco California United States 94143
    2 Connecticut Children'S Medical Center Hartford Connecticut United States 06106
    3 University Of Florida Gainesville Florida United States 32610
    4 Johns Hopkins School Of Medicine Baltimore Maryland United States 21287
    5 Boston Childrens Hospital Boston Massachusetts United States 02115
    6 Mount Sinai School Of Medicine New York New York United States 10029
    7 Children'S Hospital Of Philadelphia Philadelphia Pennsylvania United States 19104
    8 Rhode Island Hospital Providence Rhode Island United States 02903
    9 University Of Texas Southwestern Medical Center Dallas Texas United States 75390
    10 Local Institution Buenos Aires Argentina 1425
    11 Local Institution Bruxelles Belgium 1200
    12 Local Institution Porto Alegre Rio Grande Do Sul Brazil 90035
    13 Local Institution Sco Paulo Sao Paulo Brazil 05403
    14 Local Institution Toronto Ontario Canada M5G 1X8
    15 Local Institution Seoul Korea, Republic of 135-710
    16 Local Institution Seoul Korea, Republic of 138-736
    17 Local Institution Taipei Taiwan 100
    18 Local Institution London Greater London United Kingdom SE5 9RS
    19 Local Institution Birmingham West Midlands United Kingdom B4 6NH

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00423891
    Other Study ID Numbers:
    • AI463-028
    First Posted:
    Jan 18, 2007
    Last Update Posted:
    May 2, 2018
    Last Verified:
    Mar 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Entecavir

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 64 enrolled. 48 treated. Participants received a minimum of 48 weeks study drug but depending on response to drug, could remain on treatment for up to a total of 120 weeks. Participants were to receive post dosing follow up after last dose, for a total of 5 years on-study (on and off study drug).
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with less than (<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with greater than (>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Period Title: Enrolled
    STARTED 35 21 8
    COMPLETED 24 19 5
    NOT COMPLETED 11 2 3
    Period Title: Enrolled
    STARTED 24 19 5
    COMPLETED 22 19 5
    NOT COMPLETED 2 0 0
    Period Title: Enrolled
    STARTED 22 18 5
    COMPLETED 20 15 3
    NOT COMPLETED 2 3 2

    Baseline Characteristics

    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C) Total
    Arm/Group Description Participants with less than (<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with greater than (>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks. Total of all reporting groups
    Overall Participants 24 19 5 48
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    9.2
    (5.41)
    11.0
    (4.42)
    8.8
    (5.02)
    9.9
    (4.98)
    Age, Customized (participants) [Number]
    ≥ 2 years to ≤ 6 years
    7
    29.2%
    3
    15.8%
    2
    40%
    12
    25%
    >6 years to ≤ 12 years
    9
    37.5%
    7
    36.8%
    2
    40%
    18
    37.5%
    >12 years to ≤18 years
    8
    33.3%
    9
    47.4%
    1
    20%
    18
    37.5%
    Sex: Female, Male (Count of Participants)
    Female
    14
    58.3%
    7
    36.8%
    2
    40%
    23
    47.9%
    Male
    10
    41.7%
    12
    63.2%
    3
    60%
    25
    52.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    17
    70.8%
    10
    52.6%
    5
    100%
    32
    66.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    5.3%
    0
    0%
    1
    2.1%
    Black or African American
    0
    0%
    2
    10.5%
    0
    0%
    2
    4.2%
    White
    5
    20.8%
    6
    31.6%
    0
    0%
    11
    22.9%
    More than one race
    1
    4.2%
    0
    0%
    0
    0%
    1
    2.1%
    Unknown or Not Reported
    1
    4.2%
    0
    0%
    0
    0%
    1
    2.1%
    Region of Enrollment (participants) [Number]
    United States
    10
    41.7%
    5
    26.3%
    1
    20%
    16
    33.3%
    Taiwan
    3
    12.5%
    0
    0%
    0
    0%
    3
    6.3%
    Canada
    1
    4.2%
    0
    0%
    0
    0%
    1
    2.1%
    Argentina
    3
    12.5%
    0
    0%
    0
    0%
    3
    6.3%
    Belgium
    1
    4.2%
    1
    5.3%
    0
    0%
    2
    4.2%
    Brazil
    1
    4.2%
    3
    15.8%
    0
    0%
    4
    8.3%
    United Kingdom
    2
    8.3%
    1
    5.3%
    0
    0%
    3
    6.3%
    Korea, Republic of
    3
    12.5%
    9
    47.4%
    4
    80%
    16
    33.3%
    Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) (log10 IU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 IU/mL]
    7.92
    (0.864)
    7.74
    (0.856)
    7.96
    (0.238)
    7.85
    (0.812)
    Alanine Aminotransferase (ALT) (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    142.8
    (85.18)
    125.7
    (67.96)
    44.6
    (22.96)
    125.8
    (78.83)

    Outcome Measures

    1. Secondary Outcome
    Title Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
    Description Cmax and Cmin were derived from plasma concentration of ETV versus time and measured in nanograms per milliliters (ng/mL). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. Note: PK parameters were summarized for only Groups A and B. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
    Time Frame Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in Groups A and B who received study drug and had PK assessment.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B)
    Arm/Group Description Participants with less than (<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with greater than (>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
    Measure Participants 24 19
    Cmax of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
    8.07
    (24)
    16.03
    (8)
    Cmax of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
    6.29
    (25)
    19.01
    (15)
    Cmax of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
    5.11
    (27)
    11.32
    (37)
    Cmin of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
    0.244
    (32)
    0.468
    (17)
    Cmin of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
    0.320
    (22)
    0.497
    (32)
    Cmin of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
    0.271
    (25)
    0.455
    (25)
    2. Secondary Outcome
    Title Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort
    Description Tmax was derived from plasma concentration of ETV versus time and measured in hours (h). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. Age categories presented below: participants age as of first day of dosing. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
    Time Frame Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in Groups A and B who received study drug and had PK assessment.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B)
    Arm/Group Description Participants with less than (<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with greater than (>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
    Measure Participants 24 19
    Tmax of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
    0.50
    1.00
    Tmax of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
    0.57
    0.72
    Tmax of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
    0.78
    0.52
    3. Secondary Outcome
    Title Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
    Description Area under the Curve (AUC) was derived from plasma concentration of ETV versus time. AUC(TAU) was calculated by log- and linear trapezoidal summations, TAU = 24 hours, and was measured in nanograms*hours per milliliter (ng*h/mL). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
    Time Frame Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in Groups A and B who received study drug and had PK assessment.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with greater than (>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
    Measure Participants 24 19
    AUC(TAU) of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
    18.69
    (21)
    42.26
    (27)
    AUC(TAU) of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
    20.42
    (20)
    41.50
    (21)
    AUC(TAU) of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
    15.96
    (22)
    35.36
    (24)
    4. Secondary Outcome
    Title Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
    Description CLT/F was calculated by dividing the dose of ETV by AUC(TAU) of ETV and was measured in liters per hour (L/h). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
    Time Frame At 2 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in Groups A and B who received study drug and had PK assessment.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
    Measure Participants 24 19
    CLT/F of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
    11.40
    (2.564)
    12.31
    (3.102)
    CLT/F of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
    22.66
    (6.134)
    21.67
    (6.940)
    CLT/F of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
    31.92
    (6.429)
    28.95
    (6.496)
    5. Secondary Outcome
    Title Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
    Description Hepatitis B virus DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS TaqMan - high pure system (HPS) assay and was reported in international units per milliliter (IU/mL). Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    1
    4.2%
    0
    0%
    0
    0%
    Week 24
    10
    41.7%
    3
    15.8%
    0
    0%
    Week 36
    11
    45.8%
    6
    31.6%
    0
    0%
    Week 48
    14
    58.3%
    9
    47.4%
    0
    0%
    Week 96
    8
    33.3%
    11
    57.9%
    2
    40%
    6. Secondary Outcome
    Title Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
    Description HBeAg loss: HBeAg negative. The method used for the detection of HBe Ag was the DiaSorin - Anti HBe enzyme immunoassay kit. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    3
    12.5%
    0
    0%
    0
    0%
    Week 24
    4
    16.7%
    1
    5.3%
    0
    0%
    Week 36
    5
    20.8%
    1
    5.3%
    0
    0%
    Week 48
    10
    41.7%
    3
    15.8%
    0
    0%
    Week 96
    5
    20.8%
    2
    10.5%
    0
    0%
    7. Secondary Outcome
    Title Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
    Description HBsAg loss: HBsAg negative. The method used for detection of HBsAg was the ADVIA Centaur iImmunoassay system. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    0
    0%
    0
    0%
    0
    0%
    Week 24
    0
    0%
    0
    0%
    0
    0%
    Week 36
    1
    4.2%
    0
    0%
    0
    0%
    Week 48
    1
    4.2%
    0
    0%
    0
    0%
    Week 96
    0
    0%
    0
    0%
    0
    0%
    8. Secondary Outcome
    Title Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
    Description HBe seroconversion: loss of HBeAg (HBeAg negative) with positive HB e antibodies (HBeAb), ie both the presence of HBeAb and the absence of HBeAg. The method used for the detection HBeAg seroconversion was the DiaSorin - Anti HBe enzyme immunoassay kit. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline through Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    3
    12.5%
    0
    0%
    0
    0%
    Week 24
    4
    16.7%
    1
    5.3%
    0
    0%
    Week 36
    5
    20.8%
    1
    5.3%
    0
    0%
    Week 48
    10
    41.7%
    3
    15.8%
    0
    0%
    Week 96
    5
    20.8%
    1
    5.3%
    0
    0%
    9. Primary Outcome
    Title Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment
    Description 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. Medical Dictionary for Regulatory Activities (MedDRA) version 16.0 was used.
    Time Frame Day 1 to Week 120

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug. On-treatment period began on the first day of study therapy and ended 5 days after the last dose of study therapy.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Serious Adverse Events (n=24, 19, 5)
    2
    8.3%
    0
    0%
    0
    0%
    Discontinuations Due to AEs (n=24,19,5)
    0
    0%
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLD = 6 IU/mL). Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    1
    4.2%
    0
    0%
    0
    0%
    Week 24
    6
    25%
    1
    5.3%
    0
    0%
    Week 36
    7
    29.2%
    5
    26.3%
    0
    0%
    Week 48
    13
    54.2%
    6
    31.6%
    0
    0%
    Week 96
    8
    33.3%
    8
    42.1%
    1
    20%
    11. Secondary Outcome
    Title Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLQ = 29 IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline through Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    1
    4.2%
    0
    0%
    0
    0%
    Week 24
    9
    37.5%
    2
    10.5%
    0
    0%
    Week 36
    10
    41.7%
    5
    26.3%
    0
    0%
    Week 48
    14
    58.3%
    7
    36.8%
    0
    0%
    Week 96
    8
    33.3%
    8
    42.1%
    2
    40%
    12. Secondary Outcome
    Title Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
    Description HB s Ag seroconversion: loss of HBsAg (HBsAg negative) and presence of HB s antibodies (HBsAb). The method used for the detection of HBsAg seroconversion was the ADVIA Centaur iImmunoassay system. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline through Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    0
    0%
    0
    0%
    0
    0%
    Week 24
    0
    0%
    0
    0%
    0
    0%
    Week 36
    0
    0%
    0
    0%
    0
    0%
    Week 48
    0
    0%
    0
    0%
    0
    0%
    Week 96
    0
    0%
    0
    0%
    0
    0%
    13. Secondary Outcome
    Title Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
    Description PDR was defined as confirmed HBV DNA < 50 IU/mL plus confirmed HBeAg seroconversion on 2 sequential measurements at least 14 days apart. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Week 12
    0
    0%
    0
    0%
    0
    0%
    Week 24
    4
    16.7%
    0
    0%
    0
    0%
    Week 36
    4
    16.7%
    1
    5.3%
    0
    0%
    Week 48
    7
    29.2%
    3
    15.8%
    0
    0%
    Week 96
    3
    12.5%
    1
    5.3%
    0
    0%
    14. Secondary Outcome
    Title Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. HBV DNA log10 changes from baseline were summarized over time.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of study drug, and had a measurement at baseline and at the specific analysis week.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Week 12
    -4.45
    (0.2418)
    -3.89
    (0.1592)
    -3.80
    (0.4657)
    Week 24
    -5.30
    (0.2744)
    -4.85
    (0.2900)
    -3.89
    (0.5440)
    Week 36
    -5.61
    (0.2580)
    -5.14
    (0.2604)
    -3.90
    (0.2499)
    Week 48
    -5.86
    (0.2176)
    -5.36
    (0.3032)
    -4.32
    (0.4794)
    Week 96
    -6.30
    (0.2576)
    -5.86
    (0.2222)
    -5.79
    (0.5308)
    15. Secondary Outcome
    Title Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
    Description Normalization in ALT= ALT ≤ 1.0*upper limit of normal (ULN). Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    1
    5.3%
    2
    40%
    Week 4
    1
    4.2%
    1
    5.3%
    2
    40%
    Week 8
    3
    12.5%
    2
    10.5%
    2
    40%
    Week 12
    5
    20.8%
    7
    36.8%
    3
    60%
    Week 18
    15
    62.5%
    10
    52.6%
    5
    100%
    Week 24
    15
    62.5%
    12
    63.2%
    5
    100%
    Week 30
    16
    66.7%
    13
    68.4%
    5
    100%
    Week 36
    16
    66.7%
    16
    84.2%
    5
    100%
    Week 42
    16
    66.7%
    15
    78.9%
    5
    100%
    Week 48
    20
    83.3%
    18
    94.7%
    4
    80%
    Week 96
    10
    41.7%
    13
    68.4%
    3
    60%
    16. Secondary Outcome
    Title Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLQ = 29 IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
    Time Frame Baseline, Week 48, Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline >=17,200 IU/mL
    24
    100%
    19
    100%
    5
    100%
    Week 48: < 50 IU/mL
    14
    58.3%
    9
    47.4%
    0
    0%
    Week 48: 50 - < 172 IU/mL
    1
    4.2%
    2
    10.5%
    0
    0%
    Week 48: 172 - < 1720 IU/mL
    3
    12.5%
    3
    15.8%
    1
    20%
    Week 48: 1720 - < 17,200 IU/mL
    3
    12.5%
    1
    5.3%
    3
    60%
    Week 48: > = 17,200 IU/mL
    1
    4.2%
    3
    15.8%
    1
    20%
    Week 96: < 50 IU/mL
    8
    33.3%
    11
    57.9%
    2
    40%
    Week 96: 50 - < 172 IU/mL
    1
    4.2%
    1
    5.3%
    0
    0%
    Week 96: 172 - < 1720 IU/mL
    3
    12.5%
    0
    0%
    1
    20%
    Week 96: 1720 - < 17,200 IU/mL
    0
    0%
    1
    5.3%
    1
    20%
    Week 96: > = 17,200 IU/mL
    0
    0%
    0
    0%
    0
    0%
    17. Secondary Outcome
    Title Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0*ULN.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    0
    0%
    0
    0%
    0
    0%
    Week 24
    10
    41.7%
    3
    15.8%
    0
    0%
    Week 36
    11
    45.8%
    4
    21.1%
    0
    0%
    Week 48
    13
    54.2%
    9
    47.4%
    0
    0%
    Week 96
    7
    29.2%
    11
    57.9%
    2
    40%
    18. Secondary Outcome
    Title Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0*ULN. HBe seroconversion was determination of presence of HBeAb and loss of HBeAg. The method used for the detection of HBeAg seroconversion was the DiaSorin - Anti HBe enzyme immunoassay kit.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    0
    0%
    0
    0%
    0
    0%
    Week 24
    4
    16.7%
    0
    0%
    0
    0%
    Week 36
    4
    16.7%
    1
    5.3%
    0
    0%
    Week 48
    8
    33.3%
    3
    15.8%
    0
    0%
    Week 96
    3
    12.5%
    1
    5.3%
    0
    0%
    19. Secondary Outcome
    Title Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
    Description Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0*ULN. HBe seroconversion: loss of HBeAg (HBeAg negative) with positive HBeAb. The method used for the detection of HBeAg/Ab serologies was the DiaSorin enzyme immunoassay kit.
    Time Frame Baseline to Week 96

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Baseline
    0
    0%
    0
    0%
    0
    0%
    Week 12
    0
    0%
    0
    0%
    0
    0%
    Week 24
    6
    25%
    3
    15.8%
    0
    0%
    Week 36
    7
    29.2%
    3
    15.8%
    0
    0%
    Week 48
    5
    20.8%
    6
    31.6%
    0
    0%
    Week 96
    4
    16.7%
    10
    52.6%
    2
    40%
    20. Secondary Outcome
    Title Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
    Description Toxicity Scale: Division of AIDs (DAIDS) grades Version 1.0. Upper limit of normal (ULN); lower limit of normal (LLN); Cells per Liter (c/L); cells per microliter (c/µL); grams per deciliter (g/dL); milliequivalents per liter (mEq/L); cells per microliter (c/µL): Grade (Gr). Hemoglobin g/dL: Gr1:10.0-10.9;Gr2: 9.0-9.9; Gr3:7.0-8.9; Gr4: <7.0. International normalization ratio (INR): Gr1:1.1-<1.5*ULN; Gr2: 1.6-<2.0*ULN; Gr3: 2.1-3.0*ULN;Gr4: >3.0*ULN. Neutrophils/bands c/µL: Gr1;1.0-1.3*10^3; Gr2: 0.75-0.99*10^3; Gr 3: 0.50-0.749*10^3; Gr4: <0.5*10^3.
    Time Frame Day 1 to Week 120

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study therapy, and had a measurement during the on-treatment period (i.e., after the first day of study therapy through 5 days after the last dose of study therapy).
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Hemoglobin
    1
    4.2%
    0
    0%
    1
    20%
    International normalization ratio
    4
    16.7%
    3
    15.8%
    0
    0%
    Neutrophils (absolute) + bands
    3
    12.5%
    3
    15.8%
    0
    0%
    21. Secondary Outcome
    Title Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
    Description Toxicity Scale: DAIDS Version 1.0 and modified World Health Organization (WHO). Grade (Gr). ALT: Gr1:1.25-<2.5*ULN; Gr2: 2.6-<5.0 *ULN; Gr3: 5.1-10.0*ULN; Gr4:>10.0*ULN. Aspartate aminotransferase (AST): Gr1: 1.25-<2.5*ULN; Gr2:2.6-<5.0*ULN; Gr 3: 5.1-10.0*ULN; Gr4>10.0*ULN. Alkaline phosphatase: Gr1:1.25-<2.5*ULN; Gr2: 2.6-<5.0*ULN; Gr3: 5.1-10.0*ULN; Gr4: >10.0*ULN. Lipase: Gr1:1.1-<1.5*ULN;Gr2:1.6-<3.0*ULN; Gr3: 3.1-5.0*ULN; Gr4: >5.0*ULN. Creatinine: Gr1: 1.1-1.3*ULN; Gr2: 1.4-<1.8*ULN; Gr3: 1.9 - <3.4*ULN; Gr4: >=3.5*ULN. Glucose mg/dL (high): Gr1:110-<125 (Fasting)/116-<160;Gr2:126-<250 (F)/161-<250; Gr3: 251-500; Gr4: >500.Glucose (low): Gr1: 55-64; Gr2: 40 - <54; Gr3: 30-39; Gr4: <30 mg/dL.
    Time Frame Day 1 to Week 120

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of study drug, and had a measurement during the on-treatment period (i.e., after the first day of study therapy through 5 days after the last dose of study therapy).
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    ALT
    23
    95.8%
    17
    89.5%
    4
    80%
    AST
    14
    58.3%
    9
    47.4%
    1
    20%
    Alkaline Phosphatase
    3
    12.5%
    3
    15.8%
    0
    0%
    Lipase
    5
    20.8%
    12
    63.2%
    3
    60%
    Creatinine
    1
    4.2%
    1
    5.3%
    0
    0%
    Glucose, high
    3
    12.5%
    4
    21.1%
    1
    20%
    Glucose, low
    3
    12.5%
    4
    21.1%
    1
    20%
    22. Secondary Outcome
    Title Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
    Description Toxicity Scale: DAIDS Version 1.0 and modified World Health Organization (WHO) for chloride. Milliequivalents per liter (mEq/L); Grade (Gr). Chloride high (mEq/L): Gr1: 113-<117; Gr2: 117-<121; Gr3: 121-125; Gr4: >125. Potassium low (mEq/L): Gr1: 3.0-3.4; Gr2: 2.5-2.9; Gr3:2.0-<2.4; Gr4: <2.0. Potassium high: Gr1; 5.6- <6.0; Gr2: 6.1-<6.5; Gr3: 6.6-7.0; Gr4: >7.0. Sodium high (mEq/L): Gr1; 146-<150; Gr2: 151-<154; Gr3: 155-<159; Gr4: >=160.
    Time Frame Day 1 Week 120

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of study drug, and had a measurement during the on-treatment period (i.e., after the first day of study therapy through 5 days after the last dose of study therapy).
    Arm/Group Title Lamivudine (LVD)-Naive (Group A) Lamivudine (LVD)-Experienced (Group B) Nucleoside/Tide Analog (NA) - Experienced (Group C)
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    Measure Participants 24 19 5
    Chloride, high
    3
    12.5%
    0
    0%
    0
    0%
    Potassium, low
    1
    4.2%
    0
    0%
    0
    0%
    Potassium, high
    1
    4.2%
    1
    5.3%
    0
    0%
    Sodium, high
    4
    16.7%
    3
    15.8%
    0
    0%

    Adverse Events

    Time Frame From first dose to date of last dose plus 5 days, up to 120 weeks
    Adverse Event Reporting Description
    Arm/Group Title Group A LVD-naive Group B LVD-exp Group C NA-exp
    Arm/Group Description Participants with < 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants with > 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age >12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks. Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
    All Cause Mortality
    Group A LVD-naive Group B LVD-exp Group C NA-exp
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/24 (0%) 0/19 (0%) 0/5 (0%)
    Serious Adverse Events
    Group A LVD-naive Group B LVD-exp Group C NA-exp
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Infections and infestations
    Gastroenteritis 1/24 (4.2%) 0/19 (0%) 0/5 (0%)
    Pneumonia 1/24 (4.2%) 0/19 (0%) 0/5 (0%)
    Investigations
    Alanine aminotransferase increased 1/24 (4.2%) 0/19 (0%) 0/5 (0%)
    Aspartate aminotransferase increased 1/24 (4.2%) 0/19 (0%) 0/5 (0%)
    Other (Not Including Serious) Adverse Events
    Group A LVD-naive Group B LVD-exp Group C NA-exp
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/24 (87.5%) 17/19 (89.5%) 4/5 (80%)
    Ear and labyrinth disorders
    Ear pain 0/24 (0%) 2/19 (10.5%) 0/5 (0%)
    Tinnitus 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Eye disorders
    Eye haemorrhage 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Ocular hyperaemia 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Gastrointestinal disorders
    Abdominal pain 4/24 (16.7%) 4/19 (21.1%) 1/5 (20%)
    Abdominal pain upper 2/24 (8.3%) 1/19 (5.3%) 0/5 (0%)
    Dental caries 1/24 (4.2%) 1/19 (5.3%) 0/5 (0%)
    Diarrhoea 5/24 (20.8%) 3/19 (15.8%) 1/5 (20%)
    Enteritis 1/24 (4.2%) 1/19 (5.3%) 0/5 (0%)
    Faeces soft 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Flatulence 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Gastrooesophageal reflux disease 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Mouth ulceration 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Nausea 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Odynophagia 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Tooth impacted 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Vomiting 2/24 (8.3%) 4/19 (21.1%) 1/5 (20%)
    General disorders
    Chest pain 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Fatigue 1/24 (4.2%) 2/19 (10.5%) 0/5 (0%)
    Influenza like illness 1/24 (4.2%) 2/19 (10.5%) 0/5 (0%)
    Pyrexia 10/24 (41.7%) 5/19 (26.3%) 1/5 (20%)
    Immune system disorders
    Seasonal allergy 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Infections and infestations
    Ear infection 1/24 (4.2%) 2/19 (10.5%) 0/5 (0%)
    Gastroenteritis 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Gastroenteritis viral 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Impetigo 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Influenza 0/24 (0%) 2/19 (10.5%) 0/5 (0%)
    Lyme disease 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Molluscum contagiosum 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Mumps 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Otitis externa 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Otitis media acute 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Pharyngotonsillitis 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Sinusitis 3/24 (12.5%) 0/19 (0%) 0/5 (0%)
    Tonsillitis 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Upper respiratory tract infection 10/24 (41.7%) 3/19 (15.8%) 2/5 (40%)
    Viral upper respiratory tract infection 4/24 (16.7%) 9/19 (47.4%) 1/5 (20%)
    Injury, poisoning and procedural complications
    Fall 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Joint injury 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Ligament sprain 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Limb injury 2/24 (8.3%) 0/19 (0%) 1/5 (20%)
    Skin abrasion 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Investigations
    Blood alkaline phosphatase increased 0/24 (0%) 2/19 (10.5%) 0/5 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/24 (4.2%) 0/19 (0%) 1/5 (20%)
    Myalgia 2/24 (8.3%) 1/19 (5.3%) 0/5 (0%)
    Nervous system disorders
    Dizziness 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Headache 7/24 (29.2%) 5/19 (26.3%) 0/5 (0%)
    Product Issues
    Product taste abnormal 1/24 (4.2%) 1/19 (5.3%) 0/5 (0%)
    Psychiatric disorders
    Anxiety 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Mood swings 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm 2/24 (8.3%) 0/19 (0%) 0/5 (0%)
    Cough 7/24 (29.2%) 5/19 (26.3%) 1/5 (20%)
    Epistaxis 2/24 (8.3%) 1/19 (5.3%) 0/5 (0%)
    Nasal congestion 2/24 (8.3%) 1/19 (5.3%) 0/5 (0%)
    Oropharyngeal pain 3/24 (12.5%) 1/19 (5.3%) 0/5 (0%)
    Rhinorrhoea 3/24 (12.5%) 1/19 (5.3%) 1/5 (20%)
    Skin and subcutaneous tissue disorders
    Acne 0/24 (0%) 2/19 (10.5%) 0/5 (0%)
    Dermatitis allergic 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Dermatitis bullous 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Pruritus 0/24 (0%) 1/19 (5.3%) 0/5 (0%)
    Rash 2/24 (8.3%) 2/19 (10.5%) 1/5 (20%)
    Rash macular 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Rash maculo-papular 0/24 (0%) 0/19 (0%) 1/5 (20%)
    Rash pruritic 0/24 (0%) 1/19 (5.3%) 0/5 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00423891
    Other Study ID Numbers:
    • AI463-028
    First Posted:
    Jan 18, 2007
    Last Update Posted:
    May 2, 2018
    Last Verified:
    Mar 1, 2018