Hepatitis B, ChronicPhase 3DEFINENCT00410202
Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus
A Phase 3 study testing Entecavir, Tenofovir and Adefovir in people with Hepatitis B, Chronic, run by Bristol-Myers Squibb at 67 sites in 18 countries.
Trial summary
The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Entecavir, Tenofovir and Adefovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 629 participants
- Where
- 67 sitesin 18 countries
- Study dates
- Mar 2008to Jul 2012
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Evidence of lamivudine (LVD) resistance
- Subjects must have a history of previous LVD treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S)
- Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV) infection
- Compensated liver function and must have met ALL of the following criteria:International normalization ratio (INR) ≤ 1.5; Serum albumin ≥ 3 g/dL (≥ 30 g/L); Serum total bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L)
- HBV DNA > 1.72 x 10*4* IU/mL (approximately 10*5* copies/mL)
- Documentation of hepatitis B e antigen (HBeAg) positive and hepatitis B e antibody (HBeAb) negative status at screening
Show all 11Show fewer
- alanine aminotransferase (ALT) ≤ 10 * upper limit of normal (ULN) at screening
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized
- WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post menopausal is defined as:
- Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the start of investigational product
Who cannot join
- Evidence of decompensated cirrhosis
- Coinfection with human immunodeficiency virus, hepatitis C virus , or hepatitis D virus
- Women who are pregnant or breastfeeding
- Sexually active fertile men not using effective birth control if their partners were WOCBP
- Laboratory values out of protocol-specified range
Trial locations and contacts
67 sites in 18 countries.
67 sites in 18 countries
South Korea27 sites
Local Institution
Ansan-si, Gyeonggi-do, 425-707
Local Institution
Anyang-si, Gyeonggi-do, 431-070
Local Institution
Bucheon-si, Gyeonggi-do, 420767
Local Institution
Chuncheon, 200-704
Local Institution
Daegu, 700-721
Local Institution
Gangneung, 210-711
Local Institution
Incheon, Jung-Gu, 400-711
Local Institution
Incheon, 405-760
Local Institution
Koyang, Ilsanseo Gu, 411-706
Local Institution
Pusan, 602-739
Local Institution
Seongnam-si, Gyeonggi-do, 463 712
Local Institution
Seoul, Dongdaemun-Gu, 130-702
Local Institution
Seoul, Nowon-Gu, 139-872
Local Institution
Seoul, 110-744
Local Institution
Seoul, 120-752
Local Institution
Seoul, 135-710
Local Institution
Seoul, 135-720
Local Institution
Seoul, 136-705
Local Institution
Seoul, 137-040
Local Institution
Seoul, 138-736
Local Institution
Seoul, 143-729
Local Institution
Seoul, 152-703
Local Institution
Seoul, 156-755
Local Institution
Suwon, Gyeonggi-do, 442-723
Local Institution
Suwon, 443-721
Local Institution
Ulsan, Donggu, 682-714
Local Institution
Yangsan, 626770
India7 sites
Local Institution
Ahmedabad, 380006
Local Institution
Chandigarh, 160012
Local Institution
Indore, 452014
Local Institution
Lucknow, Uttar Pradesh, 226014
Local Institution
Ludhiana, 141001
Local Institution
New Delhi, 110002
Local Institution
Vellore, 632004
Poland5 sites
Local Institution
Chorzów, 41-500
Local Institution
Kielce, 25-317
Local Institution
Lodz, 91-347
Local Institution
Lublin, 20-081
Local Institution
Warsaw, 01-201
Russia4 sites
Local Institution
Moscow, 105275
Local Institution
Moscow, 115446
Local Institution
Saint Petersburg, 190103
Local Institution
Saint Petersburg, 191167
Taiwan4 sites
Local Institution
Kaohsiung City, 80756
Local Institution
Tainan R.o.c., 70403
Local Institution
Taipei, 100
Local Institution
Taoyuan, 333
Hong Kong3 sites
Local Institution
Hong Kong, Hong Kong
Local Institution
Shatin, New Territories
Local Institution
Tai Po
Australia2 sites
Local Institution
Concord, New South Wales, 2139
Local Institution
Randwick, New South Wales, 2031
Malaysia2 sites
Local Institution
Kota Kinabalu, Sabah, 88586
Local Institution
Kuala Lumpur, 50603
Philippines2 sites
Local Institution
Cebu City, 6000
Local Institution
Manila, 1502
Thailand2 sites
Local Institution
Bangkok, 10700
Local Institution
Chiang Mai, 50200
Turkey (Türkiye)2 sites
Local Institution
Bornova Izmir, 35100
Local Institution
Trabzon, 610808
United States1 site
University Of Connecticut Health Center
Farmington, Connecticut, 06030
About this study
Official title: A Comparative Study of Entecavir vs. Adefovir Plus Lamivudine vs Combination Entecavir Plus Adefovir in Lamivudine-resistant Chronic Hepatitis B Subjects: The DEFINE Study
The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine
- Conditions
- Hepatitis B, Chronic
- Being tested
- Entecavir, Tenofovir, Adefovir, Lamivudine
- 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, 1mg, once daily, 100 weeks
TenofovirDrug
Also called Viread
Tablets, Oral, 300 mg, once daily
AdefovirDrug
Also called Hepsera
Tablets, Oral, 10mg, once daily, 100 weeks
LamivudineDrug
Also called Epivir
Tablets, Oral, 100mg, once daily, 100 weeks
| Study group | Role | What they receive |
|---|---|---|
| Entecavir | Active comparator | With the option of adding tenofovir at week 48. (This does not apply to Korea) Receives: Drug: Entecavir; Drug: Tenofovir |
| Adefovir + Lamivudine | Active comparator | Not described Receives: Drug: Adefovir; Drug: Lamivudine |
| Entecavir + Adefovir | Active comparator | Not described Receives: Drug: Entecavir; Drug: Adefovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.
Measured: Week 48
Secondary outcomes (24)
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. HBV DNA < 50 IU/mL = approximately 300 copies/mL. Percentage n/N: n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.
Measured: Week 96
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.
Measured: Week 48
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.
Measured: Week 96
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.
Measured: Week 48
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest amount or concentration of analyte in a sample, which can be reliably detected, but not necessarily quantified.
Measured: Week 96
Percentage of Participants With HBV DNA by PCR Category at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay.
Measured: Week 48
Percentage of Participants With HBV DNA by PCR Category at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay.
Measured: Week 96
Change in Mean log10 From Baseline in HBV DNA at Week 48
HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load, negative values means reduction.
Measured: Baseline, Week 48
Change in Mean log10 From Baseline in HBV DNA at Week 96
HBV DNA was analyzed by PCR, using the Roche COBAS® TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load.
Measured: Baseline, Week 96
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48
ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 or 48 U/L.
Measured: Week 48
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96
ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 U/L.
Measured: Baseline, Week 96
Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Measured: Week 48
Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Measured: Week 96
Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Measured: Week 48
Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Measured: Week 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Measured: Week 48
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Measured: Week 96
Percentage of Participants With HBsAg Seroconversion at Week 48
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Measured: Week 48
Percentage of Participants With HBsAg Seroconversion at Week 96
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Measured: Week 96
Cumulative Probability of Emergent Genotypic Resistance at Year 1
yr=year. Cumulative probability (CP): Ptotal=1-(1-Pyr1)*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An "event" is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).
Measured: Year 1
Cumulative Probability of Emergent Genotypic Resistance at Year 2
Cumulative probability (CP): Ptotal=1-(1-Pyr1)*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An "event" is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).
Measured: Year 2
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. Grade 1 = mild, Grade 2= moderate, Grade 3 = severe, Grade 4 = life threatening/disabling, Grade 5 = death.
Measured: From start of study therapy through Week 100 + 5 days
Number of Participants With Laboratory Abnormalities: Hematology
Criteria for hematology abnormalities were: Hemoglobin: <=11.0 g/dL; White Blood Cells: <4000/mm^3; Absolute Neutrophils (includes absolute bands): <1500/mm^3; Platelets: <=99,000/mm^3; International Normalized Ratio: ≥ 1.5 and ≥ 0.5 from baseline.
Measured: From start of study through Week 100 + 5 days
Number of Participants With Laboratory Abnormalities: Serum Chemistry
ULN=upper limit of normal (Normal ranges are Central lab data and vary according to the site). ALT:>1.25*ULN, AST:>1.25*ULN, ALP:>1.25*ULN, Total Bilirubin:>1.1*ULN, Serum Lipase:>1.10*ULN, Creatinine:>1.1*ULN, Blood Urea Nitrogen:1.25*ULN, Hyperglycemia:>116 mg/dL, Hypoglycemia:<64 mg/dL, Hyponatremia:<132meq/L, Hypokalemia:<3.4 meq/L, Albumin:≥1g/dL decrease from baseline, <3 g/dL; Hypernatremia:>148 meq/L, Hyperkalemia:>5.6 meq/L, Hypokalemia:<3.4 meq/L, Hyperchloremia:>113 meq/L, Hypochloremia:<93 meq/L; ALT flare: on treatment (OT), >2*Baseline and >10*ULN; off treatment (OF), 2*end of dosing value and >10*ULN
Measured: On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2006 (estimated)
- Study startMar 2008
- Primary completionJan 2011
- Study completionJul 2012
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 Hepatitis B, ChronicStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 629 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
- NCT00410202
- Sponsor's protocol ID
- AI463-111
- Acronym
- DEFINE
- Status last verified
- Oct 2013
- First submitted
- 11 Dec 2006
- Last updated
- 21 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative Study of Entecavir vs. Adefovir Plus Lamivudine vs Combination Entecavir Plus Adefovir in Lamivudine-resistant Chronic Hepatitis B Subjects: The DEFINE Study
- ClinicalTrials.gov ID
- NCT00410202
- Acronym / sponsor ID
- DEFINE / AI463-111
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 629 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Mar 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 12 Dec 2006 (estimated)
- Results
- Posted 4 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Entecavir | Active comparator | Drug: Entecavir, Drug: TenofovirWith the option of adding tenofovir at week 48. (This does not apply to Korea) |
| Adefovir + Lamivudine | Active comparator | Drug: Adefovir, Drug: Lamivudine |
| Entecavir + Adefovir | Active comparator | Drug: Entecavir, Drug: Adefovir |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Evidence of lamivudine (LVD) resistance
- Subjects must have a history of previous LVD treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S)
- Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV) infection
- Compensated liver function and must have met ALL of the following criteria:International normalization ratio (INR) ≤ 1.5; Serum albumin ≥ 3 g/dL (≥ 30 g/L); Serum total bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L)
- HBV DNA > 1.72 x 10*4* IU/mL (approximately 10*5* copies/mL)
Key exclusion criteria (5 listed)
- Evidence of decompensated cirrhosis
- Coinfection with human immunodeficiency virus, hepatitis C virus , or hepatitis D virus
- Women who are pregnant or breastfeeding
- Sexually active fertile men not using effective birth control if their partners were WOCBP
- Laboratory values out of protocol-specified range
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, 1mg, once daily, 100 weeks | Drug | Entecavir, Entecavir + Adefovir |
| TenofovirAlso: VireadTablets, Oral, 300 mg, once daily | Drug | Entecavir |
| AdefovirAlso: HepseraTablets, Oral, 10mg, once daily, 100 weeks | Drug | Adefovir + Lamivudine, Entecavir + Adefovir |
| LamivudineAlso: EpivirTablets, Oral, 100mg, once daily, 100 weeks | Drug | Adefovir + Lamivudine |
Primary outcome
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48
Time frame: Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.
24 secondary outcomes
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96
Time frame: Week 96
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
Time frame: Week 48
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96
Time frame: Week 96
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48
Time frame: Week 48
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96
Time frame: Week 96
Percentage of Participants With HBV DNA by PCR Category at Week 48
Time frame: Week 48
Percentage of Participants With HBV DNA by PCR Category at Week 96
Time frame: Week 96
Change in Mean log10 From Baseline in HBV DNA at Week 48
Time frame: Baseline, Week 48
Change in Mean log10 From Baseline in HBV DNA at Week 96
Time frame: Baseline, Week 96
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48
Time frame: Week 48
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96
Time frame: Baseline, Week 96
Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)
Time frame: Week 48
Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)
Time frame: Week 96
Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)
Time frame: Week 48
Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)
Time frame: Week 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Time frame: Week 48
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96
Time frame: Week 96
Percentage of Participants With HBsAg Seroconversion at Week 48
Time frame: Week 48
Percentage of Participants With HBsAg Seroconversion at Week 96
Time frame: Week 96
Cumulative Probability of Emergent Genotypic Resistance at Year 1
Time frame: Year 1
Cumulative Probability of Emergent Genotypic Resistance at Year 2
Time frame: Year 2
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Time frame: From start of study therapy through Week 100 + 5 days
Number of Participants With Laboratory Abnormalities: Hematology
Time frame: From start of study through Week 100 + 5 days
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Time frame: On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
67 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Entecavir, Tenofovir and Adefovir in people with Hepatitis B, Chronic, run by Bristol-Myers Squibb at 67 sites in 18 countries.
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 11 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 21 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 67 sites in South Korea, India, Poland, Russia, Taiwan and 13 more countries. 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 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 4 Jul 2012). 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 With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48 (time frame: Week 48). 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 21 Nov 2013.