Chronic Hepatitis BPhase 3NCT00316719

Adefovir Dipivoxil In Compensated Chronic Hepatitis B Patients

A Phase 3 study testing LAM group and ADV group in people with Chronic Hepatitis B, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 16 to 64 years
Conditions the study is for: Chronic Hepatitis B
What is being tested?: LAM group and ADV group
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 105 participants
Where: No sites listed yet
Study dates: Jan 2006to Jan 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 64 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Who cannot join

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.

About this study

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

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.

Conditions: Chronic Hepatitis B
Being tested: LAM group, ADV group
Keywords: treatment naive, CHB, adefovir, monotherapy
Medical subject headings: Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LAM groupDrug
Also called Lamivudine
Subjects took one LAM 100mg tablet orally once daily and one ADV placebo tablet orally once daily.
ADV groupDrug
Also called adefovir dipivoxil
Subjects took one ADV 10mg tablet orally once daily and one LAM placebo tablet orally once daily.

Study groups in NCT00316719
Study group	Role	What they receive
Adefovir Dipivoxil (ADV)	Experimental	Not described Receives: Drug: ADV group
Lamivudine (LAM)	Active comparator	Not described Receives: Drug: LAM group

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Baseline and Week 52

Secondary outcomes (12)

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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Week 52
Mean Alanine Aminotransferase (ALT) Level at Week 52
Summary statistics were displayed for serum ALT.
Measured: 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
Measured: Week 52
Time to Onset of ALT Normalization
Time to onset of ALT normalization was summarized using the Kaplan-Meier method.
Measured: 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
Measured: Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2006Jan 2008

First posted21 Apr 2006 (estimated)
Study startJan 2006
Primary completionJan 2008
Study completionJan 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 105 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00316719
Sponsor's protocol ID: ADF105220
Status last verified: Oct 2009
First submitted: 19 Apr 2006
Last updated: 6 Oct 2009
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

All Chronic Hepatitis B trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase III Study of Adefovir Dipivoxil Tablets in Patients With Compensated Chronic Hepatitis B -Comparative Study Against Lamivudine-
ClinicalTrials.gov ID: NCT00316719
Acronym / sponsor ID: ADF105220
Conditions: Chronic Hepatitis B
Keywords: treatment naive, CHB, adefovir, monotherapy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 105 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: Jan 2006
Primary completion: Jan 2008 (actual)
Study completion: Jan 2008 (actual)
First posted: 21 Apr 2006 (estimated)
Results: Posted 3 Aug 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Adefovir Dipivoxil (ADV)	Experimental	Drug: ADV group
Lamivudine (LAM)	Active comparator	Drug: LAM group

Who may qualify

Ages: 16 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LAM groupAlso: LamivudineSubjects took one LAM 100mg tablet orally once daily and one ADV placebo tablet orally once daily.	Drug	Lamivudine (LAM)
ADV groupAlso: adefovir dipivoxilSubjects took one ADV 10mg tablet orally once daily and one LAM placebo tablet orally once daily.	Drug	Adefovir Dipivoxil (ADV)

Primary outcome

Mean Change From Baseline in Hepatitis B Virus (HBV) DNA at Week 52
Time frame: Baseline and 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

12 secondary outcomes

Percentage of Participants With HBV DNA Loss (<400 Copies/mL) at Week 52
Time frame: Week 52
Time to Onset of HBV DNA Loss (< 400 Copies/mL)
Time frame: From Baseline to Week 52
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 52
Time frame: Week 52
Percentage of Participants With Hepatitis B e Antigen/Antibody (HBeAg/Ab) Seroconversion at Week 52
Time frame: Week 52
Time to Onset of HBeAg Loss
Time frame: From Baseline to Week 52
Time to Onset of HBeAg/Ab Seroconversion
Time frame: From Baseline to Week 52
Percentage of Participants With Hepatitis B s Antigen (HBsAg) Loss at Week 52
Time frame: Week 52
Percentage of Participants With Hepatitis B s Antigen/ Antibody (HBsAg/Ab) Seroconversion at Week 52
Time frame: Week 52
Mean Alanine Aminotransferase (ALT) Level at Week 52
Time frame: Week 52
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 52
Time frame: Week 52
Time to Onset of ALT Normalization
Time frame: From Baseline to Week 52
Rate of Emergence of Resistant Virus at Week 52
Time frame: Week 52

Results and safety

Results posted to the registry on 3 Aug 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Adefovir (ADV)	52	50
Lamivudine (LAM)	53	47

Primary outcome: Mean Change From Baseline in Hepatitis B Virus (HBV) DNA at Week 52

Time frame: Baseline and Week 52. Mean (Standard Deviation). Unit: log10 copies/mL

Measure	Adefovir (ADV) n = 50	Lamivudine (LAM) n = 52
Value	-3.69 (1.169)	-3.40 (1.896)

Adefovir (ADV) vs Lamivudine (LAM): Mean Difference (Net): -0.33 (95% CI -0.94 to 0.28), p <0.001, ANCOVA

Population analysed: Per Protocol Set (PPS): participants in the Full Analysis Set (all subjects who entered the study, received at least one dose of investigational product, and had at least one efficacy assessment after the treatment initiation) population with no major protocol violations

12 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Adefovir (ADV)	0 of 52 (0%)	39 of 52 (75%)	Not reported
Lamivudine (LAM)	4 of 53 (7.5%)	47 of 53 (88.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2009.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Chronic Hepatitis B

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LAM group and ADV group in people with Chronic Hepatitis B, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Hepatitis B Virus (HBV) DNA at Week 52 (time frame: Baseline and Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00316719.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2009.