Trial Outcomes & Findings for Safety and Efficacy of Adefovir Dipivoxil in Children and Adolescents With Chronic Hepatitis B (NCT NCT00095121)

Last Updated: 2012-05-22

Results Overview

In the absence of biopsy data from these pediatric participants, this endpoint enables assessments of drug effect on viral replication and the underlying degree of inflammation in the liver.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

173 participants

Primary outcome timeframe

Week 48

Results posted on

2012-05-22

Participant Flow

First participant screened on 17 May 2004; first participant randomized on 21 June 2004. Participants from Gilead pharmacokinetics Study GS-02-517 were allowed to enroll regardless of screening serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) or alanine aminotransferase (ALT) concentration if they met all other entry criteria.

Participant milestones

Participant milestones
Measure	ADV - ADV Once daily treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. The adefovir dipivoxil (ADV) baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind \[DB\] ADV \[ADV-ADV group\]). Additionally, ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240). Lamivudine was to be added to the open-label ADV regimen of subjects between 12 and \<18 years old who had prior lamivudine exposure and who had a serum HBV DNA concentration \>= 1000 copies/mL at 2 consecutive study visits at or after Study Week 96.	PLB - ADV Placebo (PLB) was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group. The ADV baseline was defined as the day of first dose of ADV (ie, Week 48 for those originally randomized to placebo \[PLB-ADV group\]). Additionally, ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the PLB-ADV group could receive only up to 192 weeks of open-label (OL) ADV treatment (ADV Week 192). Lamivudine was to be added to the open-label ADV regimen of subjects between 12 and \<18 years old who had prior lamivudine exposure and who had a serum HBV DNA concentration \>= 1000 copies/mL at 2 consecutive study visits at or after Study Week 96.
Double-Blind (Study Weeks 0 Through 48) STARTED	115	58
Double-Blind (Study Weeks 0 Through 48) COMPLETED	112	58
Double-Blind (Study Weeks 0 Through 48) NOT COMPLETED	3	0
Open-Label (Study Weeks 49 Through 240) STARTED	108	54
Open-Label (Study Weeks 49 Through 240) Received Lamivudine (LAM) After Week 96	21	11
Open-Label (Study Weeks 49 Through 240) COMPLETED	46	35
Open-Label (Study Weeks 49 Through 240) NOT COMPLETED	62	19

Reasons for withdrawal

Reasons for withdrawal
Measure	ADV - ADV Once daily treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. The adefovir dipivoxil (ADV) baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind \[DB\] ADV \[ADV-ADV group\]). Additionally, ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240). Lamivudine was to be added to the open-label ADV regimen of subjects between 12 and \<18 years old who had prior lamivudine exposure and who had a serum HBV DNA concentration \>= 1000 copies/mL at 2 consecutive study visits at or after Study Week 96.	PLB - ADV Placebo (PLB) was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group. The ADV baseline was defined as the day of first dose of ADV (ie, Week 48 for those originally randomized to placebo \[PLB-ADV group\]). Additionally, ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the PLB-ADV group could receive only up to 192 weeks of open-label (OL) ADV treatment (ADV Week 192). Lamivudine was to be added to the open-label ADV regimen of subjects between 12 and \<18 years old who had prior lamivudine exposure and who had a serum HBV DNA concentration \>= 1000 copies/mL at 2 consecutive study visits at or after Study Week 96.
Double-Blind (Study Weeks 0 Through 48) Adverse Event	1	0
Double-Blind (Study Weeks 0 Through 48) Not Compliant	2	0

Baseline Characteristics

Safety and Efficacy of Adefovir Dipivoxil in Children and Adolescents With Chronic Hepatitis B

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ADV - ADV n=115 Participants Once daily treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. The ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to DB ADV \[ADV-ADV group\]). Additionally, ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	PLB - ADV n=58 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group. The ADV baseline was defined as the day of first dose of ADV (ie, Week 48 for those originally randomized to placebo \[PLB-ADV group\]). Additionally, ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the PLB-ADV group could receive only up to 192 weeks of ADV treatment (ADV Week 192).	Total n=173 Participants Total of all reporting groups
Genotype HBV Genotype A	51 participants n=93 Participants	32 participants n=4 Participants	83 participants n=27 Participants
Age, Categorical <=18 years	115 Participants n=93 Participants	58 Participants n=4 Participants	173 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age Continuous	10.8 years STANDARD_DEVIATION 4.33 • n=93 Participants	10.7 years STANDARD_DEVIATION 3.94 • n=4 Participants	10.8 years STANDARD_DEVIATION 4.19 • n=27 Participants
Sex: Female, Male Female	41 Participants n=93 Participants	19 Participants n=4 Participants	60 Participants n=27 Participants
Sex: Female, Male Male	74 Participants n=93 Participants	39 Participants n=4 Participants	113 Participants n=27 Participants
Genotype HBV Genotype B	13 participants n=93 Participants	5 participants n=4 Participants	18 participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	114 Participants n=93 Participants	58 Participants n=4 Participants	172 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Asian	29 Participants n=93 Participants	12 Participants n=4 Participants	41 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	11 Participants n=93 Participants	3 Participants n=4 Participants	14 Participants n=27 Participants
Race (NIH/OMB) White	70 Participants n=93 Participants	41 Participants n=4 Participants	111 Participants n=27 Participants
Race (NIH/OMB) More than one race	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	35 participants n=93 Participants	13 participants n=4 Participants	48 participants n=27 Participants
Region of Enrollment Belgium	6 participants n=93 Participants	3 participants n=4 Participants	9 participants n=27 Participants
Region of Enrollment Germany	11 participants n=93 Participants	8 participants n=4 Participants	19 participants n=27 Participants
Region of Enrollment Poland	48 participants n=93 Participants	27 participants n=4 Participants	75 participants n=27 Participants
Region of Enrollment Spain	4 participants n=93 Participants	4 participants n=4 Participants	8 participants n=27 Participants
Region of Enrollment United Kingdom	11 participants n=93 Participants	3 participants n=4 Participants	14 participants n=27 Participants
Body Mass Index (Males)	19.3 kg/cm^2 STANDARD_DEVIATION 4.04 • n=93 Participants	19.7 kg/cm^2 STANDARD_DEVIATION 4.87 • n=4 Participants	19.4 kg/cm^2 STANDARD_DEVIATION 4.33 • n=27 Participants
Body Mass Index (Females)	17.8 kg/cm^2 STANDARD_DEVIATION 3.68 • n=93 Participants	17.7 kg/cm^2 STANDARD_DEVIATION 3.76 • n=4 Participants	17.7 kg/cm^2 STANDARD_DEVIATION 3.67 • n=27 Participants
Prior Exposure to Hepatitis B Treatment Yes	64 participants n=93 Participants	33 participants n=4 Participants	97 participants n=27 Participants
Prior Exposure to Hepatitis B Treatment No	51 participants n=93 Participants	25 participants n=4 Participants	76 participants n=27 Participants
HBV DNA	8.74 log10 copies/mL STANDARD_DEVIATION 0.894 • n=93 Participants	8.67 log10 copies/mL STANDARD_DEVIATION 1.016 • n=4 Participants	8.71 log10 copies/mL STANDARD_DEVIATION 0.935 • n=27 Participants
Hepatitis B Surface Antigen (HBsAg) Negative	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Hepatitis B Surface Antigen (HBsAg) Positive	115 participants n=93 Participants	58 participants n=4 Participants	173 participants n=27 Participants
Antibody to HBsAg (HBsAb) Negative	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Antibody to HBsAg (HBsAb) Positive	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Antibody to HBsAg (HBsAb) Not Done	115 participants n=93 Participants	58 participants n=4 Participants	173 participants n=27 Participants
Hepatitis B e Antigen (HBeAg) Negative	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Hepatitis B e Antigen (HBeAg) Positive	113 participants n=93 Participants	57 participants n=4 Participants	170 participants n=27 Participants
Antibody to HBeAg (HBeAb) Negative	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Antibody to HBeAg (HBeAb) Positive	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Antibody to HBeAg (HBeAb) Not Done	113 participants n=93 Participants	57 participants n=4 Participants	170 participants n=27 Participants
ALT	111 U/L STANDARD_DEVIATION 81.6 • n=93 Participants	99 U/L STANDARD_DEVIATION 52.8 • n=4 Participants	107 U/L STANDARD_DEVIATION 73.3 • n=27 Participants
ALT >= Upper Limit of Normal (ULN)	108 participants n=93 Participants	56 participants n=4 Participants	164 participants n=27 Participants
ALT <ULN	7 participants n=93 Participants	2 participants n=4 Participants	9 participants n=27 Participants
ALT as Multiple of ULN <=median (2.265)	57 participants n=93 Participants	30 participants n=4 Participants	87 participants n=27 Participants
ALT as Multiple of ULN >median (2.265)	58 participants n=93 Participants	28 participants n=4 Participants	86 participants n=27 Participants
ALT Category Alanine aminotransferase <=ULN	8 participants n=93 Participants	2 participants n=4 Participants	10 participants n=27 Participants
ALT Category ULN <alanine aminotransferase <=2*ULN	37 participants n=93 Participants	25 participants n=4 Participants	62 participants n=27 Participants
ALT Category 2ULN <alanine aminotransferase <=5ULN	52 participants n=93 Participants	26 participants n=4 Participants	78 participants n=27 Participants
ALT Category Alanine aminotransferase >5*ULN	18 participants n=93 Participants	5 participants n=4 Participants	23 participants n=27 Participants
ALT (Multiples of ULN)	2.9 multiples STANDARD_DEVIATION 2.03 • n=93 Participants	2.6 multiples STANDARD_DEVIATION 1.40 • n=4 Participants	2.8 multiples STANDARD_DEVIATION 1.85 • n=27 Participants
Genotype HBV Genotype C	10 participants n=93 Participants	4 participants n=4 Participants	14 participants n=27 Participants
Genotype HBV Genotype D	35 participants n=93 Participants	14 participants n=4 Participants	49 participants n=27 Participants
Genotype HBV Genotype E	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Genotype HBV Genotype F	2 participants n=93 Participants	0 participants n=4 Participants	2 participants n=27 Participants
Prior Use of Other Hepatitis B Medications No	107 participants n=93 Participants	56 participants n=4 Participants	163 participants n=27 Participants
Genotype Not Done	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Time Since HBV Diagnosis	6.8 years until enrollment STANDARD_DEVIATION 4.12 • n=93 Participants	6.8 years until enrollment STANDARD_DEVIATION 4.06 • n=4 Participants	6.8 years until enrollment STANDARD_DEVIATION 4.09 • n=27 Participants
Mode of HBV Acquisition Perinatal transmission or within 1st year of life	47 participants n=93 Participants	24 participants n=4 Participants	71 participants n=27 Participants
Mode of HBV Acquisition Unknown	37 participants n=93 Participants	21 participants n=4 Participants	58 participants n=27 Participants
Mode of HBV Acquisition Childhood acquisition after 1st year of life	19 participants n=93 Participants	8 participants n=4 Participants	27 participants n=27 Participants
Mode of HBV Acquisition Transfusion or exposure to infected blood products	8 participants n=93 Participants	3 participants n=4 Participants	11 participants n=27 Participants
Mode of HBV Acquisition Other	4 participants n=93 Participants	2 participants n=4 Participants	6 participants n=27 Participants
Mode of HBV Acquisition Intravenous drug user	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Mode of HBV Acquisition Missing	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Mode of HBV Acquisition Sexual contact with HBV infected person	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Symptoms of Acute Hepatitis B Yes	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Symptoms of Acute Hepatitis B No	113 participants n=93 Participants	56 participants n=4 Participants	169 participants n=27 Participants
Hepatitis B Flares (Acute Exacerbation) Yes	12 participants n=93 Participants	4 participants n=4 Participants	16 participants n=27 Participants
Hepatitis B Flares (Acute Exacerbation) No	103 participants n=93 Participants	54 participants n=4 Participants	157 participants n=27 Participants
Current Alcohol Consumption Yes	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants
Current Alcohol Consumption No	115 participants n=93 Participants	58 participants n=4 Participants	173 participants n=27 Participants
Any Prior Hepatitis B Medication Yes	66 participants n=93 Participants	33 participants n=4 Participants	99 participants n=27 Participants
Any Prior Hepatitis B Medication No	49 participants n=93 Participants	25 participants n=4 Participants	74 participants n=27 Participants
Prior Use of Famciclovir Yes	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Prior Use of Famciclovir No	115 participants n=93 Participants	57 participants n=4 Participants	172 participants n=27 Participants
Prior Use of Lamivudine Yes	46 participants n=93 Participants	23 participants n=4 Participants	69 participants n=27 Participants
Prior Use of Lamivudine No	69 participants n=93 Participants	35 participants n=4 Participants	104 participants n=27 Participants
Prior Use of Interferon Alpha Yes	52 participants n=93 Participants	28 participants n=4 Participants	80 participants n=27 Participants
Prior Use of Interferon Alpha No	63 participants n=93 Participants	30 participants n=4 Participants	93 participants n=27 Participants
Prior Use of ADV Yes	4 participants n=93 Participants	4 participants n=4 Participants	8 participants n=27 Participants
Prior Use of ADV No	111 participants n=93 Participants	54 participants n=4 Participants	165 participants n=27 Participants
Prior Use of Other Hepatitis B Medications Yes	8 participants n=93 Participants	2 participants n=4 Participants	10 participants n=27 Participants

PRIMARY outcome

Timeframe: Week 48

Population: All randomized participants who received \>= 1 dose study medication. If either endpoint was missing a Week 48 value, Week 44 value was substituted and used in the combined endpoint. If participant did not have serum HBV DNA value at Weeks 44 and 48 or ALT value at Weeks 44 and 48, then participant was considered a failure for the Week-48 analysis.

In the absence of biopsy data from these pediatric participants, this endpoint enables assessments of drug effect on viral replication and the underlying degree of inflammation in the liver.

Outcome measures

Outcome measures
Measure	ADV - ADV n=115 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=58 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 1000 Copies/mL (Polymerase Chain Reaction [PCR]-Based Assay) and Normal Alanine Aminotransferase (ALT) at Week 48 (Missing = Failure) Baseline	0 percentage of participants	0 percentage of participants
Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 1000 Copies/mL (Polymerase Chain Reaction [PCR]-Based Assay) and Normal Alanine Aminotransferase (ALT) at Week 48 (Missing = Failure) Week 24	5 percentage of participants	0 percentage of participants
Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 1000 Copies/mL (Polymerase Chain Reaction [PCR]-Based Assay) and Normal Alanine Aminotransferase (ALT) at Week 48 (Missing = Failure) Week 48 or End of Double-blind Treatment	19 percentage of participants	2 percentage of participants

SECONDARY outcome

Timeframe: ADV baseline

Population: The OL analysis set was used for this endpoint and included any participant who took at least 1 dose of open-label ADV. Participants with missing values were considered as failures rather than excluded.

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: ADV Week 192

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment - Missing = Failure) (ADV Week 192)	15 percentage of participants	15 percentage of participants

SECONDARY outcome

Timeframe: ADV Week 240

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240)	6 percentage of participants	—

SECONDARY outcome

Timeframe: ADV baseline

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: ADV Week 192

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 192)	11 percentage of participants	13 percentage of participants

SECONDARY outcome

Timeframe: ADV Week 240

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240)	6 percentage of participants	—

SECONDARY outcome

Timeframe: ADV baseline

Population: The OL analysis set included any participant who took at least one dose of open-label ADV. This analysis set was also subdivided based on DB drug, as ADV-ADV or PLB-ADV. Analysis set included only data from participants while on study treatment.

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Adefovir (ADV) Baseline Serum HBV DNA	8.76 log10 HBV DNA copies/mL Standard Deviation 0.869	8.24 log10 HBV DNA copies/mL Standard Deviation 1.248

SECONDARY outcome

Timeframe: ADV baseline to ADV 192 weeks

Population: The OL analysis set included any participant who took at least one dose of open-label ADV. This analysis set was subdivided based on DB drug, as ADV-ADV or PLB-ADV. Analysis set included only data from participants while on study treatment.

Outcome measures

Outcome measures
Measure	ADV - ADV n=17 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=9 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Change From ADV Baseline to ADV Week 192 for Serum HBV DNA	-5.89 log10 HBV DNA copies/mL Standard Deviation 1.119	-5.41 log10 HBV DNA copies/mL Standard Deviation 1.573

SECONDARY outcome

Timeframe: ADV baseline to ADV 240 weeks

Outcome measures

Outcome measures
Measure	ADV - ADV n=7 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Change From ADV Baseline to ADV Week 240 for Serum HBV DNA	-5.87 log10 HBV DNA copies/mL Standard Deviation 1.826	—

SECONDARY outcome

Timeframe: ADV baseline

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
ADV Baseline ALT	108.69 U/L Standard Deviation 79.069	99.81 U/L Standard Deviation 97.583

SECONDARY outcome

Timeframe: ADV baseline to ADV 192 weeks

Outcome measures

Outcome measures
Measure	ADV - ADV n=17 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=8 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Change From ADV Baseline to ADV Week 192 for ALT	-66.06 U/L Standard Deviation 42.655	-38.88 U/L Standard Deviation 33.566

SECONDARY outcome

Timeframe: ADV baseline to ADV 240 weeks

Outcome measures

Outcome measures
Measure	ADV - ADV n=6 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Change From ADV Baseline to ADV Week 240 for ALT	-64.33 U/L Standard Deviation 44.742	—

SECONDARY outcome

Timeframe: ADV baseline

Population: The OL analysis set included any participant who took at least one dose of open-label ADV. This analysis set was also subdivided based on DB drug, as ADV-ADV or PLB-ADV. Participants with missing values were considered as failures rather than excluded. Analysis set included only data from participants while on study treatment.

The ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\] and Week 48 for those originally randomized to placebo \[PLB-ADV group\]). Normal ALT: 0-1 year old = \<=54 U/L; females 1-88 years old and males 1-10 years old = 8-34 U/L; males 10-88 years old = 8-43 U/L.

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Normal ALT at Adefovir Baseline (Missing = Failure)	7 percentage of participants	15 percentage of participants

SECONDARY outcome

Timeframe: ADV Week 192

Population: The OL analysis set included any participant who took at least one dose of open-label ADV. This analysis set was subdivided based on DB drug, as ADV-ADV or PLB-ADV. Participants with missing values were considered as failures rather than excluded. Analysis set included only data from participants while on study treatment.

Adefovir week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240), whereas participants in the PLB-ADV group could receive only up to 192 weeks of ADV treatment (ADV Week 192). Normal ALT: 0-1 year old = \<=54 U/L; females 1-88 years old and males 1-10 years old = 8-34 U/L; males 10-88 years old = 8-43 U/L.

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=54 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Normal ALT at ADV Week 192 (Missing = Failure)	14 percentage of participants	13 percentage of participants

SECONDARY outcome

Timeframe: ADV Week 240

Normal ALT: 0-1 year old = \<=54 U/L; females 1-88 years old and males 1-10 years old = 8-34 U/L; males 10-88 years old = 8-43 U/L.

Outcome measures

Outcome measures
Measure	ADV - ADV n=108 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Normal ALT at ADV Week 240 (Missing = Failure)	5 percentage of participants	—

SECONDARY outcome

Timeframe: Study Week 0 to Study Week 48 (double-blind period)

Population: The randomized and treated analysis set included all participants who were randomized into the study and received at least one dose of study medication. For Week 48 data; if Week 48 was missing, Week 44 was carried forward; if Week 44 was missing, missing = failure.

HBeAg loss is defined for an individual participant as HBeAg+ at ADV baseline and HBeAg- post baseline. HBeAg seroconversion is defined for an individual participant as HBeAg+ at ADV baseline and HBeAg- and hepatitis B e antibody + (anti-HBe+) post baseline.

Outcome measures

Outcome measures
Measure	ADV - ADV n=113 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=57 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss or Seroconversion by End of Blinded Treatment (Study Week 48; Randomized and Treated Analysis Set) HBeAg Loss	17 percentage of participants	5 percentage of participants
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss or Seroconversion by End of Blinded Treatment (Study Week 48; Randomized and Treated Analysis Set) Seroconversion to Anti-HBe	16 percentage of participants	5 percentage of participants

SECONDARY outcome

Timeframe: ADV baseline to ADV Week 192

Population: The OL analysis set included any participant who took at least one dose of open-label ADV. This analysis set was subdivided based on DB drug, as ADV-ADV or PLB-ADV. Participants with missing values were excluded. Analysis set included only data from participants while on study treatment.

ADV baseline = 1st ADV-dose day = Week 0 for ADV-ADV group and Week 48 for PLB-ADV group. ADV week = windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240), whereas participants in the PLB-ADV group could receive only up to 192 weeks of ADV treatment (ADV Week 192). HBeAg loss is defined per individual participant as HBeAg+ at ADV baseline and HBeAg- post baseline. HBeAg seroconversion is defined for an individual participant as HBeAg+ at ADV baseline and HBeAg- and anti-HBe+ post baseline.

Outcome measures

Outcome measures
Measure	ADV - ADV n=16 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=9 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With HBeAg Loss or Seroconversion by ADV Week 192 (Open Label Analysis Set, Participants Who Were HBeAg Positive at ADV Baseline; Missing = Excluded) HBeAg Loss	56 percentage of participants	33 percentage of participants
Percentage of Participants With HBeAg Loss or Seroconversion by ADV Week 192 (Open Label Analysis Set, Participants Who Were HBeAg Positive at ADV Baseline; Missing = Excluded) Seroconversion to Anti-HBe	44 percentage of participants	11 percentage of participants

SECONDARY outcome

Timeframe: ADV baseline to ADV Week 240

Population: The OL analysis set included any participant who took at least one dose of open-label ADV. This analysis set was subdivided based on DB drug, as ADV-ADV or PLB-ADV. Participants with missing values were excluded. Analysis set included only data from participants while on study treatment.

Per protocol, participants could discontinue study medication due to HBeAg seroconversion and remain in the study in order to evaluate the durability of seroconversion. HBeAg loss is defined for an individual participant as HBeAg+ at ADV baseline and HBeAg- post baseline. HBeAg seroconversion is defined for an individual participant as HBeAg+ at ADV baseline and HBeAg- and anti-HBe+ post baseline.

Outcome measures

Outcome measures
Measure	ADV - ADV n=6 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With HBeAg Loss or Seroconversion by ADV Week 240 (Open Label Analysis Set, Participants Who Were HBeAg Positive at ADV Baseline; Missing = Excluded) HBeAg Loss	33 percentage of participants	—
Percentage of Participants With HBeAg Loss or Seroconversion by ADV Week 240 (Open Label Analysis Set, Participants Who Were HBeAg Positive at ADV Baseline; Missing = Excluded) Seroconversion to Anti-HBe	17 percentage of participants	—

SECONDARY outcome

Timeframe: 240 weeks

Population: Last on-ADV sample through Week 240 was analyzed, and participant was excluded from the cumulative Week 240 analysis if HBV DNA value was \< 169 copies/mL at Week 240/last time point or if participant discontinued study drug but remained in study. One ADV-ADV participant had an ADV-specific, conserved-site mutation and is counted twice in the table.

Resistance surveillance was conducted annually for all participants who remained on treatment and had HBV DNA concentrations greater than or equal to the level of detection (\>= 169 copies/mL) by PCR. The last on-ADV sample for all participants in the study was analyzed in the cumulative Week 240 resistance surveillance analysis.

Outcome measures

Outcome measures
Measure	ADV - ADV n=74 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=37 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) No genotypic changes from baseline	48 Participants	18 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) Polymorphic site changes	17 Participants	12 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) Changes at conserved sites in HBV polymerase	3 Participants	3 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) Developed mutations specific to ADV/lamivudine	1 Participants	0 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) Unable to be genotyped	6 Participants	4 Participants

SECONDARY outcome

Timeframe: 240 weeks

Population: 32/173 added lamivudine from Weeks 108 - 144. Last on-ADV sample through Week 240 analyzed; participant omitted from cumulative Week 240 analysis if HBV DNA \<169 copies/mL at Week 240/last time point or stopped study drug but remained in study. 2 ADV-ADV participants had ADV/lamivudine-specific, conserved-site mutation, and counted 2x in table.

Resistance surveillance was conducted at Week 240/last on-treatment study visit for all participants who had HBV DNA concentrations greater than or equal to the level of detection (\>= 169 copies/mL) by PCR while on combination ADV + lamivudine treatment.

Outcome measures

Outcome measures
Measure	ADV - ADV n=14 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=3 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy No genotypic changes from baseline	5 Participants	1 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy Polymorphic site changes	3 Participants	1 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy Changes at conserved sites in HBV polymerase	3 Participants	1 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy Developed mutations specific to ADV and/or LAM	2 Participants	0 Participants
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy Unable to be genotyped	3 Participants	0 Participants

SECONDARY outcome

Timeframe: 240 weeks

Population: Participants who discontinued treatment because of confirmed HBeAg seroconversion in Weeks 49 to 240 were to remain in the study through Week 240 to monitor the durability of seroconversion. Any participant who formally stopped drug early and restarted, by definition, did not have durable HBeAg seroconversion.

A participant was defined to have durable HBeAg seroconversion only if she/he remained in a seroconverted state (HBeAg-, hepatitis B e antibody + \[anti-HBe+\]) from the date that she/he first seroconverted through and including her/his last study visit. This endpoint could only be assessed for participants who (HBeAg-) seroconverted on-treatment and subsequently discontinued open-label dosing.

Outcome measures

Outcome measures
Measure	ADV - ADV n=45 Participants Double-blind once daily ADV treatment: children aged 2 to \<7 years received 0.3 mg/kg oral suspension; children aged \>=7 to \<12 years received 0.25 mg/kg oral suspension; children aged \>=12 to \<18 years received 10 mg tablet. At Week 48, ADV-treated participants were offered the opportunity to receive open-label ADV for up to an additional 192 weeks (ie, OL Weeks 49 to 240). ADV baseline was defined as the day of first dose of ADV (ie, Week 0 for participants originally randomized to double-blind ADV \[ADV-ADV group\]). ADV week was defined as the windowed visit week relative to ADV baseline. Thus, participants in the ADV-ADV group could have received up to 240 weeks of ADV treatment (ADV Week 240).	Placebo (PLB) n=24 Participants Placebo was matched to adefovir dipivoxil treatment (oral suspension or tablet) by age group.
Percentage of Participants With Durable HBeAg Seroconversion	82 Percentage of participants	71 Percentage of participants

Adverse Events

ADV (Double-Blind)

Serious events: 7 serious events

Other events: 95 other events

Deaths: 0 deaths

PLB (Double-Blind)

Serious events: 5 serious events

Other events: 47 other events

Deaths: 0 deaths

ADV - ADV

Serious events: 10 serious events

Other events: 73 other events

Deaths: 0 deaths

PLB - ADV

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

John Flaherty, PharmD, Director, Clinical Research

Gilead Sciences

Phone: 650-522-5592

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication must include results in their entirety and not as individual center data. Results may be published/presented at scientific meetings. All manuscripts/abstracts must be submitted to Gilead prior to submission. Any formal publication of the study in which input of Gilead personnel exceeded that of conventional monitoring will be considered as a joint publication by the investigator and the appropriate Gilead personnel.
Publication restrictions are in place

Restriction type: OTHER