Chronic Hepatitis BPhase 4NCT00393484
A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection
A Phase 4 study testing Entecavir and Lamivudine in people with Chronic Hepatitis B, run by Bristol-Myers Squibb at 15 sites in South Korea.
Trial summary
Entecavir, 0.5 mg daily, will have clinical efficacy (assessed as an undetectable hepatitis B DNA, <300 copies/mL, by Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction assay) that is comparable (noninferior) and potentially superior to lamivudine, 100 mg once daily, in adults with hepatitis… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Entecavir and Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 15 sitesSouth Korea
- Study dates
- Feb 2007to Sep 2013
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Nucleoside and nucleotide-naive subjects with chronic HBV infection
- Hepatitis B Surface antigen(HBsAg)-positive ≥6 months
- Detectable HBsAg
- HBV DNA ≥ 105 copies/mL by PCR
- ALT 1.3 to 10 x the ULN
- HBeAg negative, anti-hepatitis B Virus E antigen antibody (anti-HBeAb) positive status
Who cannot join
None listed.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
South Korea15 sites
Local Institution
Bucheon-si, 420-717
Local Institution
Busan, 602-739
Local Institution
Chuncheon, 200-704
Local Institution
Daegu, 700-721
Local Institution
Daegu, 705-030
Local Institution
Daejeon, 301-721
Local Institution
Guri-si, 471-020
Local Institution
Jeonju, 561-180
Local Institution
Seoul, 130-702
Local Institution
Seoul, 135-270
Local Institution
Seoul, 135-710
Local Institution
Seoul, 136-705
Local Institution
Seoul, 138-040
Local Institution
Seoul, 150-950
Local Institution
Seoul, 152-050
About this study
Official title: A Phase IV Study of the Antiviral Activity and Safety of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen in Korea
Entecavir, 0.5 mg daily, will have clinical efficacy (assessed as an undetectable hepatitis B DNA, <300 copies/mL, by Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction assay) that is comparable (noninferior) and potentially superior to lamivudine, 100 mg once daily, in adults with hepatitis B e antigen-negative chronic hepatitis B virus infection.
- Conditions
- Chronic Hepatitis B
- Being tested
- Entecavir, Lamivudine Placebo, Lamivudine, Entecavir Placebo
- 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.
EntecavirDrug
Also called Baraclude, BMS-200475
Tablets, Oral, 0.5 mg, once daily (0-96 weeks) and (96-240 weeks)
Lamivudine PlaceboDrug
Capsules, Oral, 0 mg, once daily (0-96 weeks)
LamivudineDrug
Capsules, Oral, 100 mg, once daily (0-96 weeks)
Tablets, Oral, 100 mg, once daily (96-240 weeks)
Entecavir PlaceboDrug
Tablets, Oral, 0 mg, once daily (0-96 weeks)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Entecavir + Lamivudine placebo (0-96 weeks)
Entecavir (96-240 weeks) Receives: Drug: Entecavir; Drug: Lamivudine Placebo |
| Arm B | Active comparator | Lamivudine + Entecavir placebo (0-96 weeks)
Lamivudine (96-240 weeks) Receives: Drug: Lamivudine; Drug: Entecavir Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Achieved a Virologic Response at Week 24
Virologic response=Hepatitis B virus DNA <300 copies/mL by polymerase chain reaction assay.
Measured: At Week 24
Secondary outcomes (13)
Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96
The number and percentage of participants achieving the following endpoints will be tabulated at each visit through Week 240 by treatment group: HBV DNA <300 copies/mL by PCR assay; HBV DNA <10^3, <10^4, or < 10^5 copies/mL by PCR assay. Treatment comparisons will be assessed using the same method as the primary endpoint.
Measured: At Weeks 24, 48, and 96
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
Mean log10 reduction from Baseline in HBV DNA virus by the Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction (PCR) assay at Week 24. The extent of the decrease was estimated by comparing HBV DNA levels of all participants in each group with a linear regression model with covariates of treatment and baseline HBV DNA by PCR assay.
Measured: At Weeks 24, 48, 96, 144, 192, and 240
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24
Mean ALT values from baseline by laboratory test. .
Measured: At Week 24
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
Normalization of serum ALT= ≤*institutional upper limit of normal.
Measured: At Weeks 24, 48, and 96
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Most common AEs=AEs affecting ≥3 participants. Grade 3 (Severe)/Grade 4 (Very Severe)AEs per World Health Organization (WHO) criteria.Serious adverse events/deaths reported for enrolled patients regardless of treatment status.
Measured: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24
ALT flares=ALT>2*Baseline and 10*upper limit of normal. Serious adverse events/deaths reported for enrolled patients regardless of treatment status.
Measured: Start of dosing (Day 1) until end of treatment (24 weeks) + 5 days and to end of 24-week follow-up period
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
ULN=upper limit of normal; ALT=alanine transaminase. WHO criteria: Grade 3=Severe (inability to carry out usual activity); Grade 4=Very severe (debilitating or significantly incapacitating patient despite symptomatic treatment).
Measured: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to the end of the 24-week follow-up period
Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24
Vital signs assessed included blood pressure, heart rate, body temperature, and respiration rate.
Measured: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Number of Participants With Virologic Rebound at Week 24
Virologic rebound was defined as a confirmed ≥1 log10 increase in hepatitis B virus (HBV) DNA from nadir on blinded treatment (as determined by 2 sequential HBV DNA measurements or last on-treatment measurement).
Measured: At Week 24
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
Undetectable HBV DNA= <300 copies/mL by polymerase chain reaction assay
Measured: At Weeks 48, 96, 144, 192, and 240
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96
Virologic rebound was defined as a confirmed ≥1 log10 increase in HBV DNA from nadir on blinded treatment (as determined by 2 sequential HBV DNA values or last on-treatment measurement).
Measured: At 96 weeks
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Measured: Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
ULN=upper limit of normal; ALT=alanine transaminase. WHO criteria: Grade 3=Severe (inability to carry out usual activity); Grade 4=Very severe (debilitating or significantly incapacitating patient despite symptomatic treatment).
Measured: Start of dosing (Day 1) until Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2006 (estimated)
- Study startFeb 2007
- Primary completionJan 2009
- Study completionSep 2013
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 Bristol-Myers SquibbThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00393484
- Sponsor's protocol ID
- AI463-105
- Status last verified
- Nov 2014
- First submitted
- 26 Oct 2006
- Last updated
- 26 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV Study of the Antiviral Activity and Safety of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen in Korea
- ClinicalTrials.gov ID
- NCT00393484
- Acronym / sponsor ID
- AI463-105
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 27 Oct 2006 (estimated)
- Results
- Posted 18 Nov 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Entecavir, 0.5 mg daily, will have clinical efficacy (assessed as an undetectable hepatitis B DNA, <300 copies/mL, by Roche Comprehensive Bio-Analytical System Amplicor polymerase chain reaction assay) that is comparable (noninferior) and potentially superior to lamivudine, 100 mg once daily, in adults with hepatitis B e antigen-negative chronic hepatitis B virus infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Entecavir, Drug: Lamivudine PlaceboEntecavir + Lamivudine placebo (0-96 weeks) Entecavir (96-240 weeks) |
| Arm B | Active comparator | Drug: Lamivudine, Drug: Entecavir PlaceboLamivudine + Entecavir placebo (0-96 weeks) Lamivudine (96-240 weeks) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Nucleoside and nucleotide-naive subjects with chronic HBV infection
- Hepatitis B Surface antigen(HBsAg)-positive ≥6 months
- Detectable HBsAg
- HBV DNA ≥ 105 copies/mL by PCR
- ALT 1.3 to 10 x the ULN
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| EntecavirAlso: Baraclude, BMS-200475Tablets, Oral, 0.5 mg, once daily (0-96 weeks) and (96-240 weeks) | Drug | Arm A |
| Lamivudine PlaceboCapsules, Oral, 0 mg, once daily (0-96 weeks) | Drug | Arm A |
| LamivudineCapsules, Oral, 100 mg, once daily (0-96 weeks) Tablets, Oral, 100 mg, once daily (96-240 weeks) | Drug | Arm B |
| Entecavir PlaceboTablets, Oral, 0 mg, once daily (0-96 weeks) | Drug | Arm B |
Primary outcome
Percentage of Participants Who Achieved a Virologic Response at Week 24
Time frame: At Week 24
Virologic response=Hepatitis B virus DNA <300 copies/mL by polymerase chain reaction assay.
13 secondary outcomes
Number of Participants With Hepatitis B Virus (HBV) DNA <10^3, <10^4, or < 10^5 Copies/mL by Polymerase Chain Reaction (PCR) Assy at Weeks 24, 48, and 96
Time frame: At Weeks 24, 48, and 96
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
Time frame: At Weeks 24, 48, 96, 144, 192, and 240
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24
Time frame: At Week 24
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
Time frame: At Weeks 24, 48, and 96
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 24
Time frame: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Number of Participants With Elevations in Alanine Transaminase (ALT) and Aspartate Aminoaminase (AST) Levels, Elevations in ALT and AST Levels,Simultaneous Elevations in ALT and Total Bilirubin Levels, and ALT Flares at Week 24
Time frame: Start of dosing (Day 1) until end of treatment (24 weeks) + 5 days and to end of 24-week follow-up period
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
Time frame: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to the end of the 24-week follow-up period
Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24
Time frame: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Number of Participants With Virologic Rebound at Week 24
Time frame: At Week 24
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
Time frame: At Weeks 48, 96, 144, 192, and 240
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96
Time frame: At 96 weeks
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Most Common AEs, and Grade 3/4 AEs at Week 240
Time frame: Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Time frame: Start of dosing (Day 1) until Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Entecavir and Lamivudine in people with Chronic Hepatitis B, run by Bristol-Myers Squibb at 15 sites in South Korea.
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 6 inclusion and 0 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 26 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 18 Nov 2010). 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?
Percentage of Participants Who Achieved a Virologic Response at Week 24 (time frame: At Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2014.