Adefovir Dipivoxil In Compensated Chronic Hepatitis B Patients

Study Overview
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Brief Summary
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This study is designed to compare the efficacy and safety of adefovir dipivoxil 10 mg with lamivudine 100 mg in Japanese patients with compensated chronic hepatitis B over 52-week periods.

Official Title
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Phase III Study of Adefovir Dipivoxil Tablets in Patients With Compensated Chronic Hepatitis B -Comparative Study Against Lamivudine-

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: LAM group
* Drug: ADV group


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Have compensated chronic hepatitis B. Have not been treated with anti HBV agents with antiproliferative activity against. However, previous Interferon (IFN) therapy is permitted. Ability to read, understand, and sign the informed consent. Have a positive serum HBV-DNA >= 1,000,000 copies/mL and ALT level 50-500 U/L Exclusion criteria: Having or suspected of having liver cancer. Co-infected with Hepatitis C virus (HCV) or Human Immunodeficiency virus (HIV). Autoimmune hepatitis. Received any previous transplantation or having a plan for any transplantation. Existence of any serious complication, except hepatitis B.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adefovir Dipivoxil (ADV)<br> | Drug: ADV group<br>* Subjects took one ADV 10mg tablet orally once daily and one LAM placebo tablet orally once daily.<br>* Other names: adefovir dipivoxil;|
| Active Comparator: Lamivudine (LAM)<br> | Drug: LAM group<br>* Subjects took one LAM 100mg tablet orally once daily and one ADV placebo tablet orally once daily.<br>* Other names: Lamivudine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Hepatitis B Virus (HBV) DNA at Week 52 | Change from baseline was the difference of the HBV DNA copy numbers (log10) in serum collected by blood draw between baseline and Week 52 | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HBV DNA Loss (<400 Copies/mL) at Week 52 | The percentages of participants with an HBV DNA level in serum of less than 400 copies/mL, which is the lower limit of detection (HBV DNA loss) at Week 52 | Week 52 | 
| Time to Onset of HBV DNA Loss (< 400 Copies/mL) | Time to onset of an HBV DNA level in serum of less than 400 copies/mL was summarized using the Kaplan-Meier method. Regarding the Measured Values, the median time to onset and its upper limit for the ADV group and the upper limit of the median time to onset for the LAM group are non-estimable because they are not observed until the end of the study. The lower limit of the median time to onset for the ADV and LAM groups are 36.0 and 20.0, respectively. The median time to onset for the LAM group is 28.0 | From Baseline to Week 52 | 
| Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 52 | Participants with loss of Hepatitis B e antigen (HBeAg) in serum collected by blood draw: Cheminoluminescent Immuno Assay (CLIA) method | Week 52 | 
| Percentage of Participants With Hepatitis B e Antigen/Antibody (HBeAg/Ab) Seroconversion at Week 52 | Participants with loss of Hepatitis B e antigen (HBeAg) and positive for anti-Hepatitis B e antibody (HBeAb) in serum collected by blood draw: CLIA method | Week 52 | 
| Time to Onset of HBeAg Loss | Time to onset with loss of HBeAg in serum collected by blood draw was summarized using the Kaplan-Meier method.: CLIA method. Regarding the Measured Values, the median time to onset and its lower limit and its upper limit for all groups are non-estimable because they are not observed until the end of the study. | From Baseline to Week 52 | 
| Time to Onset of HBeAg/Ab Seroconversion | Time to onset of HBeAg/Ab seroconversion in serum collected by blood draw was summarized using the Kaplan-Meier method.: CLIA method. Regarding the Measured Values, the median time to onset and its lower limit and its upper limit for all groups are non-estimable because they are not observed until the end of the study. | From Baseline to Week 52 | 
| Percentage of Participants With Hepatitis B s Antigen (HBsAg) Loss at Week 52 | Participants with loss of Hepatitis B s antigen (HBsAg) in serum collected by blood draw: CLIA method | Week 52 | 
| Percentage of Participants With Hepatitis B s Antigen/ Antibody (HBsAg/Ab) Seroconversion at Week 52 | Participants with loss of Hepatitis B s antigen (HBsAg) and positive for anti-Hepatitis B s antibody (HBsAb) in serum collected by blood draw: CLIA method | Week 52 | 
| Mean Alanine Aminotransferase (ALT) Level at Week 52 | Summary statistics were displayed for serum ALT. | Week 52 | 
| Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 52 | ALT normalization was defined as an ALT value that was in the normal range (<= 45IU/L; upper limit of normal [ULN]) at Week 52 of the participants whose ALT values were abnormal (>45IU/L) at baseline | Week 52 | 
| Time to Onset of ALT Normalization | Time to onset of ALT normalization was summarized using the Kaplan-Meier method. | From Baseline to Week 52 | 
| Rate of Emergence of Resistant Virus at Week 52 | Participants with resistant mutation at Week 52. LAM resistant mutation (enzyme-linked mini-sequencing assay): rtM204I/V; ADV resistant mutation (direct sequencing assay): rtN236T or rtA181T/V in HBV DNA ; rt: reverse transcriptase gene | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment naive, CHB, adefovir, monotherapy