Chronic Hepatitis B
Conditions
Keywords
Hepatitis B, Children, Pediatric, Adefovir Dipivoxil
Brief summary
The purpose of this study is to investigate the efficacy and safety of adefovir dipivoxil for the treatment of chronic hepatitis B in children and adolescents (age 2 to less than 18 years) following 48 weeks of placebo-controlled, double-blind treatment and following an additional 192 weeks of open-label adefovir dipivoxil treatment.
Detailed description
Weeks 1 through 48 (Study Year 1): The first 48 weeks of the study were a randomized, double-blind, placebo-controlled, parallel-group treatment period. Participants were randomly assigned to treatment in a 2:1 fashion to ADV or PLB. Prior to randomization, eligible participants were classified into 1 of 6 strata based upon age at screening (2 to \< 7 years; \>= 7 to \< 12 years; \>= 12 to \< 18 years) and prior exposure to treatment for chronic hepatitis B (CHB) (prior treatment; no prior treatment). Weeks 49 through 240 (Study Years 2 through 5): At Week 48, all placebo-treated participants who did not exhibit HBeAg or hepatitis B surface antigen (HBsAg) seroconversion at Week 44, plus all ADV-treated participants, were offered the opportunity to receive open-label ADV for up to an additional 192 weeks. Any participant with HBV DNA \>= 1000 copies/mL at 2 consecutive visits 12 weeks apart was to be discontinued from open-label study treatment. The only exception was for participants in the adolescent age range with prior lamivudine experience who were allowed the opportunity to add lamivudine to ADV; similarly, if combination failed to impart suppression of HBV DNA below 1000 copies/mL (confirmed) discontinuation was necessary. All participants who discontinued study drug due to confirmed seroconversion were requested to continue to return for study visits for the remainder of the study in order to evaluate the durability of seroconversion. Participants who wished to discontinue study treatment and withdraw from the study prior to study completion were requested to return every 4 weeks for 16 weeks for posttreatment evaluations following an early termination visit. Any participants who experienced posttreatment hepatic flares during the 16-week follow-up period were to be followed every 4 weeks until their ALT levels returned to \<= 2 times the upper limit of normal (ULN) for a maximum off-treatment follow-up of 6 months. Participants who experienced a severe hepatic flare (per protocol definition) after discontinuation of ADV during the open-label treatment period may have been eligible to receive ADV for treatment of the hepatic flare (after consultation with the Gilead medical monitor).
Interventions
DRUGPlacebo (PLB)
Matching placebo
DRUGAdefovir Dipivoxil (ADV)
10-mg tablet or 2-mg/mL oral suspension
DRUGLamivudine
100-mg tablet administered according to package labeling. Lamivudine was to be added to the open-label ADV regimen of subjects with a serum HBV DNA concentration \>= 1000 copies/mL at 2 consecutive study visits at or after Study Week 96. If the HBV DNA concentration remained \>= 1000 copies/mL at 2 consecutive study visits after the addition of lamivudine, the investigator was required to discontinue all study drugs, perform the early termination ssessments, and have the subject return every 4 weeks for 16 weeks of posttreatment evaluations.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Positive HBsAg \>= 6 months prior to randomization and positive HBeAg at screening. * Serum HBV DNA greater than or equal to 1 x 100,000 copies/mL (PCR assay) at initial or confirmatory screening visit. * Serum ALT levels greater than or equal to 1.5 x ULN at both initial and confirmatory screening visits. * Compensated liver disease with anticipated survival greater than 12 months and with the following laboratory and clinical parameters within 4 weeks of baseline: \*Prothrombin time less than or equal to 1 second above normal range. \*Total bilirubin less than 1.3 mg/dL or normal direct bilirubin. \*Serum albumin greater than 3 g/dL (greater than 30 g/L). \*No clinical history of ascites, variceal bleeding, encephalopathy or splenomegaly. \*Adequate renal function defined as creatinine clearance greater than or equal to 80 mL/min (calculated using Schwartz Formula). Key
Exclusion criteria
* Received immunoglobulin, interferon or lamivudine therapy within 6 months prior to initial screening visit. * Participated in any investigational trial with any investigational compound within 2 months prior to initial screening. * Organ or bone marrow transplant recipients. * Clinical evidence of decompensated liver disease. * A Child-Pugh-Turcotte score greater than 6. * Inability to comply with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment - Missing = Failure) (ADV Week 192) | ADV Week 192 | 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). |
| Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240) | ADV Week 240 | — |
| Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) | ADV baseline | 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 \[PLB-ADV group\]). |
| Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 192) | ADV Week 192 | 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). |
| Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240) | ADV Week 240 | — |
| Adefovir (ADV) Baseline Serum HBV DNA | ADV baseline | 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 \[PLB-ADV group\]). |
| Change From ADV Baseline to ADV Week 192 for Serum HBV DNA | ADV baseline to ADV 192 weeks | 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). |
| Change From ADV Baseline to ADV Week 240 for Serum HBV DNA | ADV baseline to ADV 240 weeks | — |
| ADV Baseline ALT | ADV baseline | 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 \[PLB-ADV group\]). |
| Change From ADV Baseline to ADV Week 192 for ALT | ADV baseline to ADV 192 weeks | 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). |
| Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) | ADV baseline | 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 \[PLB-ADV group\]). |
| Percentage of Participants With Normal ALT at Adefovir Baseline (Missing = Failure) | ADV baseline | 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. |
| Percentage of Participants With Normal ALT at ADV Week 192 (Missing = Failure) | ADV Week 192 | 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. |
| Percentage of Participants With Normal ALT at ADV Week 240 (Missing = Failure) | 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. |
| 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) | Study Week 0 to Study Week 48 (double-blind period) | 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. |
| 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) | ADV baseline to ADV Week 192 | 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. |
| 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) | ADV baseline to ADV Week 240 | 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. |
| Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | 240 weeks | 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. |
| Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy | 240 weeks | 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. |
| Percentage of Participants With Durable HBeAg Seroconversion | 240 weeks | 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. |
| Change From ADV Baseline to ADV Week 240 for ALT | ADV baseline to ADV 240 weeks | — |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 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). | 115 |
| PLB - ADV 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). | 58 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind (Study Weeks 0 Through 48) | Adverse Event | 1 | 0 |
| Double-Blind (Study Weeks 0 Through 48) | Not Compliant | 2 | 0 |
Baseline characteristics
| Characteristic | PLB - ADV | ADV - ADV | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 58 Participants | 115 Participants | 173 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 10.7 years STANDARD_DEVIATION 3.94 | 10.8 years STANDARD_DEVIATION 4.33 | 10.8 years STANDARD_DEVIATION 4.19 |
| ALT <ULN | 2 participants | 7 participants | 9 participants |
| ALT >= Upper Limit of Normal (ULN) | 56 participants | 108 participants | 164 participants |
| ALT | 99 U/L STANDARD_DEVIATION 52.8 | 111 U/L STANDARD_DEVIATION 81.6 | 107 U/L STANDARD_DEVIATION 73.3 |
| ALT as Multiple of ULN <=median (2.265) | 30 participants | 57 participants | 87 participants |
| ALT as Multiple of ULN >median (2.265) | 28 participants | 58 participants | 86 participants |
| ALT Category 2*ULN <alanine aminotransferase <=5*ULN | 26 participants | 52 participants | 78 participants |
| ALT Category Alanine aminotransferase >5*ULN | 5 participants | 18 participants | 23 participants |
| ALT Category Alanine aminotransferase <=ULN | 2 participants | 8 participants | 10 participants |
| ALT Category ULN <alanine aminotransferase <=2*ULN | 25 participants | 37 participants | 62 participants |
| ALT (Multiples of ULN) | 2.6 multiples STANDARD_DEVIATION 1.4 | 2.9 multiples STANDARD_DEVIATION 2.03 | 2.8 multiples STANDARD_DEVIATION 1.85 |
| Antibody to HBeAg (HBeAb) Negative | 0 participants | 0 participants | 0 participants |
| Antibody to HBeAg (HBeAb) Not Done | 57 participants | 113 participants | 170 participants |
| Antibody to HBeAg (HBeAb) Positive | 1 participants | 2 participants | 3 participants |
| Antibody to HBsAg (HBsAb) Negative | 0 participants | 0 participants | 0 participants |
| Antibody to HBsAg (HBsAb) Not Done | 58 participants | 115 participants | 173 participants |
| Antibody to HBsAg (HBsAb) Positive | 0 participants | 0 participants | 0 participants |
| Any Prior Hepatitis B Medication No | 25 participants | 49 participants | 74 participants |
| Any Prior Hepatitis B Medication Yes | 33 participants | 66 participants | 99 participants |
| Body Mass Index (Females) | 17.7 kg/cm^2 STANDARD_DEVIATION 3.76 | 17.8 kg/cm^2 STANDARD_DEVIATION 3.68 | 17.7 kg/cm^2 STANDARD_DEVIATION 3.67 |
| Body Mass Index (Males) | 19.7 kg/cm^2 STANDARD_DEVIATION 4.87 | 19.3 kg/cm^2 STANDARD_DEVIATION 4.04 | 19.4 kg/cm^2 STANDARD_DEVIATION 4.33 |
| Current Alcohol Consumption No | 58 participants | 115 participants | 173 participants |
| Current Alcohol Consumption Yes | 0 participants | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 114 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Genotype HBV Genotype A | 32 participants | 51 participants | 83 participants |
| Genotype HBV Genotype B | 5 participants | 13 participants | 18 participants |
| Genotype HBV Genotype C | 4 participants | 10 participants | 14 participants |
| Genotype HBV Genotype D | 14 participants | 35 participants | 49 participants |
| Genotype HBV Genotype E | 2 participants | 3 participants | 5 participants |
| Genotype HBV Genotype F | 0 participants | 2 participants | 2 participants |
| Genotype Not Done | 1 participants | 1 participants | 2 participants |
| HBV DNA | 8.67 log10 copies/mL STANDARD_DEVIATION 1.016 | 8.74 log10 copies/mL STANDARD_DEVIATION 0.894 | 8.71 log10 copies/mL STANDARD_DEVIATION 0.935 |
| Hepatitis B e Antigen (HBeAg) Negative | 1 participants | 2 participants | 3 participants |
| Hepatitis B e Antigen (HBeAg) Positive | 57 participants | 113 participants | 170 participants |
| Hepatitis B Flares (Acute Exacerbation) No | 54 participants | 103 participants | 157 participants |
| Hepatitis B Flares (Acute Exacerbation) Yes | 4 participants | 12 participants | 16 participants |
| Hepatitis B Surface Antigen (HBsAg) Negative | 0 participants | 0 participants | 0 participants |
| Hepatitis B Surface Antigen (HBsAg) Positive | 58 participants | 115 participants | 173 participants |
| Mode of HBV Acquisition Childhood acquisition after 1st year of life | 8 participants | 19 participants | 27 participants |
| Mode of HBV Acquisition Intravenous drug user | 0 participants | 0 participants | 0 participants |
| Mode of HBV Acquisition Missing | 0 participants | 0 participants | 0 participants |
| Mode of HBV Acquisition Other | 2 participants | 4 participants | 6 participants |
| Mode of HBV Acquisition Perinatal transmission or within 1st year of life | 24 participants | 47 participants | 71 participants |
| Mode of HBV Acquisition Sexual contact with HBV infected person | 0 participants | 0 participants | 0 participants |
| Mode of HBV Acquisition Transfusion or exposure to infected blood products | 3 participants | 8 participants | 11 participants |
| Mode of HBV Acquisition Unknown | 21 participants | 37 participants | 58 participants |
| Prior Exposure to Hepatitis B Treatment No | 25 participants | 51 participants | 76 participants |
| Prior Exposure to Hepatitis B Treatment Yes | 33 participants | 64 participants | 97 participants |
| Prior Use of ADV No | 54 participants | 111 participants | 165 participants |
| Prior Use of ADV Yes | 4 participants | 4 participants | 8 participants |
| Prior Use of Famciclovir No | 57 participants | 115 participants | 172 participants |
| Prior Use of Famciclovir Yes | 1 participants | 0 participants | 1 participants |
| Prior Use of Interferon Alpha No | 30 participants | 63 participants | 93 participants |
| Prior Use of Interferon Alpha Yes | 28 participants | 52 participants | 80 participants |
| Prior Use of Lamivudine No | 35 participants | 69 participants | 104 participants |
| Prior Use of Lamivudine Yes | 23 participants | 46 participants | 69 participants |
| Prior Use of Other Hepatitis B Medications No | 56 participants | 107 participants | 163 participants |
| Prior Use of Other Hepatitis B Medications Yes | 2 participants | 8 participants | 10 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 29 Participants | 41 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 70 Participants | 111 Participants |
| Region of Enrollment Belgium | 3 participants | 6 participants | 9 participants |
| Region of Enrollment Germany | 8 participants | 11 participants | 19 participants |
| Region of Enrollment Poland | 27 participants | 48 participants | 75 participants |
| Region of Enrollment Spain | 4 participants | 4 participants | 8 participants |
| Region of Enrollment United Kingdom | 3 participants | 11 participants | 14 participants |
| Region of Enrollment United States | 13 participants | 35 participants | 48 participants |
| Sex: Female, Male Female | 19 Participants | 41 Participants | 60 Participants |
| Sex: Female, Male Male | 39 Participants | 74 Participants | 113 Participants |
| Symptoms of Acute Hepatitis B No | 56 participants | 113 participants | 169 participants |
| Symptoms of Acute Hepatitis B Yes | 2 participants | 2 participants | 4 participants |
| Time Since HBV Diagnosis | 6.8 years until enrollment STANDARD_DEVIATION 4.06 | 6.8 years until enrollment STANDARD_DEVIATION 4.12 | 6.8 years until enrollment STANDARD_DEVIATION 4.09 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 95 / 115 | 47 / 58 | 73 / 108 | 46 / 54 |
| serious Total, serious adverse events | 7 / 115 | 5 / 58 | 10 / 108 | 3 / 54 |
Outcome results
Primary
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)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Placebo (PLB) | 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 |
| Placebo (PLB) | 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 | 0 percentage of participants |
| Placebo (PLB) | 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 | 2 percentage of participants |
Comparison: After unblinding the results, due to the small number of responders in the placebo group, it was determined that a statistical exact test would be more appropriate in the evaluation of treatment group differences than the originally planned 95% confidence intervals of the difference between the groups. Therefore, the results were analyzed by study visit, and a Fisher exact test was used to evaluate treatment differences between the adefovir dipivoxil and placebo groups.p-value: <0.001Fisher Exact
Secondary
Adefovir (ADV) Baseline Serum HBV DNA
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 \[PLB-ADV group\]).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | Adefovir (ADV) Baseline Serum HBV DNA | 8.76 log10 HBV DNA copies/mL | Standard Deviation 0.869 |
| Placebo (PLB) | Adefovir (ADV) Baseline Serum HBV DNA | 8.24 log10 HBV DNA copies/mL | Standard Deviation 1.248 |
Secondary
ADV Baseline ALT
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 \[PLB-ADV group\]).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | ADV Baseline ALT | 108.69 U/L | Standard Deviation 79.069 |
| Placebo (PLB) | ADV Baseline ALT | 99.81 U/L | Standard Deviation 97.583 |
Secondary
Change From ADV Baseline to ADV Week 192 for ALT
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | Change From ADV Baseline to ADV Week 192 for ALT | -66.06 U/L | Standard Deviation 42.655 |
| Placebo (PLB) | Change From ADV Baseline to ADV Week 192 for ALT | -38.88 U/L | Standard Deviation 33.566 |
Secondary
Change From ADV Baseline to ADV Week 192 for Serum HBV DNA
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | Change From ADV Baseline to ADV Week 192 for Serum HBV DNA | -5.89 log10 HBV DNA copies/mL | Standard Deviation 1.119 |
| Placebo (PLB) | Change From ADV Baseline to ADV Week 192 for Serum HBV DNA | -5.41 log10 HBV DNA copies/mL | Standard Deviation 1.573 |
Secondary
Change From ADV Baseline to ADV Week 240 for ALT
Time frame: ADV baseline to ADV 240 weeks
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | Change From ADV Baseline to ADV Week 240 for ALT | -64.33 U/L | Standard Deviation 44.742 |
Secondary
Change From ADV Baseline to ADV Week 240 for Serum HBV DNA
Time frame: ADV baseline to ADV 240 weeks
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | Change From ADV Baseline to ADV Week 240 for Serum HBV DNA | -5.87 log10 HBV DNA copies/mL | Standard Deviation 1.826 |
Secondary
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Polymorphic site changes | 17 Participants |
| Adefovir Dipivoxil (ADV) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Developed mutations specific to ADV/lamivudine | 1 Participants |
| Adefovir Dipivoxil (ADV) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Changes at conserved sites in HBV polymerase | 3 Participants |
| Adefovir Dipivoxil (ADV) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Unable to be genotyped | 6 Participants |
| Adefovir Dipivoxil (ADV) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | No genotypic changes from baseline | 48 Participants |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Unable to be genotyped | 4 Participants |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | No genotypic changes from baseline | 18 Participants |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Polymorphic site changes | 12 Participants |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Changes at conserved sites in HBV polymerase | 3 Participants |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) | Developed mutations specific to ADV/lamivudine | 0 Participants |
Secondary
Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy | Unable to be genotyped | 0 Participants |
| Placebo (PLB) | 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 | 1 Participants |
| Placebo (PLB) | Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy | Polymorphic site changes | 1 Participants |
| Placebo (PLB) | 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 | 1 Participants |
| Placebo (PLB) | 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 | 0 Participants |
Secondary
Percentage of Participants With 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | Percentage of Participants With Durable HBeAg Seroconversion | 82 Percentage of participants |
| Placebo (PLB) | Percentage of Participants With Durable HBeAg Seroconversion | 71 Percentage of participants |
Secondary
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)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Placebo (PLB) | 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 | 33 percentage of participants |
| Placebo (PLB) | 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 | 11 percentage of participants |
Secondary
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)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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
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 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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Adefovir Dipivoxil (ADV) | 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 |
| Placebo (PLB) | 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 | 5 percentage of participants |
| Placebo (PLB) | 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 | 5 percentage of participants |
p-value: 0.051Fisher Exact
p-value: 0.051Fisher Exact
Secondary
Percentage of Participants With Normal ALT at Adefovir Baseline (Missing = Failure)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | Percentage of Participants With Normal ALT at Adefovir Baseline (Missing = Failure) | 7 percentage of participants |
| Placebo (PLB) | Percentage of Participants With Normal ALT at Adefovir Baseline (Missing = Failure) | 15 percentage of participants |
Secondary
Percentage of Participants With Normal ALT at ADV Week 192 (Missing = Failure)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | Percentage of Participants With Normal ALT at ADV Week 192 (Missing = Failure) | 14 percentage of participants |
| Placebo (PLB) | Percentage of Participants With Normal ALT at ADV Week 192 (Missing = Failure) | 13 percentage of participants |
Secondary
Percentage of Participants With Normal ALT at ADV Week 240 (Missing = Failure)
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.
Time frame: 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 considered as failures rather than excluded. Analysis set included only data from participants while on study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | Percentage of Participants With Normal ALT at ADV Week 240 (Missing = Failure) | 5 percentage of participants |
Secondary
Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline)
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 \[PLB-ADV group\]).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) | 0 percentage of participants |
| Placebo (PLB) | Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) | 0 percentage of participants |
Secondary
Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment - Missing = Failure) (ADV Week 192)
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).
Time frame: ADV Week 192
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Placebo (PLB) | 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 |
Secondary
Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240)
Time frame: ADV Week 240
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | 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
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline)
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 \[PLB-ADV group\]).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) | 0 percentage of participants |
| Placebo (PLB) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) | 0 percentage of participants |
Secondary
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 192)
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).
Time frame: ADV Week 192
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |
| Placebo (PLB) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 192) | 13 percentage of participants |
Secondary
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240)
Time frame: ADV Week 240
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adefovir Dipivoxil (ADV) | 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 |