Hepatitis B VirusPhase 2NCT01438424

Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials

A Phase 2 study testing Entecavir and Lamivudine in people with Hepatitis B Virus and HBV, run by Bristol-Myers Squibb.

Completed

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

Trial summary

The purpose of this study is to provide entecavir to participants who have completed another entecavir trial without achieving virologic response or who relapsed during postdosing follow-up. Read more about this study

Who is it for?: Ages 16 years and older
Conditions the study is for: Hepatitis B Virus, HBV
What is being tested?: Entecavir and Lamivudine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,053 participants
Where: No sites listed yet
Study dates: Jan 2001to Apr 2011
Phase: Phase 2
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

Age of 16 years and older
Receipt of entecavir or lamivudine in a previous entecavir study.
Participants who were, based on their response to entecavir:
Virologic nonresponders at Week 48
Partial virologic responders who became nonresponders during the second year of treatment
Partial virologic responders at Week 96

Show all 13Show fewer

Complete responders who relapsed during postdosing follow-up
Decompensated liver disease in AI463-048 that met 1 or more of the following criteria:
Nonresponse to adefovir after at least 24 weeks of treatment
Partial response to adefovir after 96 weeks of treatment
Complete response to adefovir after relapsing during postdosing follow-up
Demonstrated intolerance to adefovir
Except for those participants enrolled from AI463-048, compensated liver disease.

Who cannot join

HIV coinfection
Receiving nephrotoxic or hepatotoxic agents
Ongoing opportunistic infections
Hemoglobin level <11.0 g/dL except for those enrolled from AI463-048
Platelet count <70,000 mm^3 except for those enrolled from AI463-048
Absolute granulocyte count <1,500 cells/mm^3

Show all 9Show fewer

Recent history of pancreatitis (within 24 weeks prior to first dose of therapy)
Current evidence of ascites requiring paracentesis, hepatic encephalopathy, or variceal bleeding, except for those enrolled from AI463-048
Known history of allergy to nucleoside analogues.

About this study

Official title: A Preliminary Assessment of Safety and Antiviral Activity of Open-label Entecavir in Subjects With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials

The purpose of this study is to provide entecavir to participants who have completed another entecavir trial without achieving virologic response or who relapsed during postdosing follow-up.

Conditions: Hepatitis B Virus, HBV
Being tested: Entecavir, Lamivudine
Medical subject headings: Hepatitis B

What participants receive

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

EntecavirDrug
Also called Baraclude
Tablets, Oral, 1.0 mg, once daily
LamivudineDrug
Oral, 100 mg, daily

Study groups in NCT01438424
Study group	Role	What they receive
Entecavir, 1.0 mg, with or without lamivudine	Experimental	Not described Receives: Drug: Entecavir; Drug: Lamivudine

What is being measured

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

Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs
An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment. An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine transaminase; ULN=upper limit of normal.
Measured: Continuously from Day 1 through Week 240
Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240
Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0; Gr 2=8.0-<9.5; Gr 3=6.5-<8.0; Gr 4=<6.5 White blood cells (cells/mm^3): Gr 1=2,500-<4,000; Gr 2=1,000-<2,500; Gr 3=800-<1,000; Gr 4=<800. Neutrophils (cells/mm^3): Gr 1=1000-<1500; Gr 2=750-<1000; Gr 3=500-<750; Gr 4=<500. Platelets (cells/mm^3): Gr 1=75,000-99,000; Gr 2=50,000-<75,000; Gr 3=20,000-<50,000; Gr 4=<20,000. Prothrombin time (seconds): Gr 1=1.01-<1.26*ULN; Gr 2=1.26-<1.51 *ULN; Gr 3=1.51-3*ULN; Gr 4=>3*ULN. INR: Gr 1=1.24-1.5; Gr 2=1.5-2; Gr 3=2-3; Gr 4=>3. INR=international normalized ratio; ULN=upper limit of normal. .
Measured: Day 1 of treatment through Week 240
Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing
Amylase: Grade 1=1.10-<1.40*ULN; Grade 2=1.40-< 2.10*ULN; Grade 3=2.10-5.00*ULN; Grade 4=>5.00*ULN. Lipase: Grade 1.1-<1.4*ULN; Grade 2=1.4-<2.1*ULN; Grade 3=2.1-5.0*ULN; Grade 4=>5.0*ULN. Creatinine: Grade 1=1.10-< 1.60*ULN; Grade 2=1.60-<3.10*ULN; Grade 3=3.10-6.00*ULN; Grade 4=>6.00*ULN. Blood urea nitrogen (BUN): Grade 1=1.25-<2.60*ULN; Grade 2=2.60-<5.10*ULN; Grade 3=5.10-10*ULN; Grade 4=>10*ULN. ULN=upper limit of normal.
Measured: Day 1 of treatment through Week 240
Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing
Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-<90; Gr 3=80-<85; Gr 4=40-<80. Hyperchloremia: Gr 1=113-<117; Gr 2=117-<121; Gr 3=121-125; Gr 4>125. Hypocarbia: Gr 1=19-21; Gr 2=15-<19; Gr 3=41-45; Gr 4=>45. Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=>45. Hyponatremia: Gr 1=130-132; Gr 2=123-<130; Gr 3=116-<123; Gr 4<116. Hypernatremia: Gr 1=148-<151; Gr 2=151-<158; Gr 3=158-165; Gr 4=>165. Hypokalemia: Gr 1=3-3.4; Gr 2=2.5-<3; Gr 3=2-<2.5; Gr 4=<2. Hyperkalemia: Gr 1=5.6-<6.1; G2=6.1-<6.6; Gr 3=6.6-7; Gr 4=>7. Hypoglycemia: Gr 1=55-64; Gr 2=40-<55; Gr 3=30-< 40; G4=-<30. Hyperglycemia: Gr 1=116-<161; Gr 2=161-<251; Gr 3=251-500; Gr 4>500.
Measured: Day 1 of treatment through Week 240
Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. AST=aspartate aminotransferase; ULN=upper limit of normal.
Measured: Continuously from Day 1 through Week 144
Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine aminotransferase; ULN=upper limit of normal.
Measured: Continuously from Day 1 through Week 192
Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)
The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.
Measured: End of dosing to Week 48 off-treatment follow-up

Secondary outcomes (19)

Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay
Measured: Study entry to Week 192
Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay
Measured: Study entry to Week 192
Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay
Observed values.
Measured: Baseline to Week 192
Overall Study: Mean HBV DNA Level by PCR Assay
Measured: Study entry to Week 216
Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)
Observed values.
Measured: Study entry to Week 216
Overall Study: Percentage of Participants With HBeAg Seroconversion
Observed values. Seroconversion=negative HBeAg with detectable anti-HBe antibody.
Measured: Study entry to Week 216
Overall Study: Mean Alanine Transaminase (ALT) Levels
Observed values.
Measured: Study entry to Week 216
Overall Study: Percentage of Participants Who Achieved ALT Normalization
ULN=upper limit of normal. ALT normalization=ALT levels ≤1.0*ULN.
Measured: Study entry to Week 216
Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)
The Knodell Histologic Activity Index scores stage of necrosis and grade of inflammation in liver biopsies. Components are necrosis near the portal vein, intralobular degeneration and focal necrosis, portal inflammation, and fibrosis. The 4 components are scored from 1 to 4 and 1 to 10 (necrosis near the portal vein) and combined for a total score, with 22 being the highest possible score. Higher the score for each component=greater liver damage. Histologic improvement=a ≥2-point reduction in total Knodell score and no worsening in fibrosis. Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell necroinflammatory scores ≥2.
Measured: Baseline to Week 192
Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)
The Ishak Modification for Hepatic Activity Index (HAI) scores necroinflammatory activity in chronic hepatitis. 0=no fibrosis, 1=fibrosis expansion of some portal areas, 2=fibrosis expansion of most portal areas, 3=fibrosis expansion of most portal areas with occasional bridging, 4=fibrosis expansion of portal areas with marked bridging, 5=incomplete cirrhosis, 6=probable or definite cirrhosis. Higher score=more severe necrosis. Improvement in fibrosis=≥1-point reduction in HAI score. Cohort participants had to have adequate baseline and long-term biopsy samples and baseline Knodell scores ≥2.
Measured: Baseline to Week 192
Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay
Measured: Baseline to Week 144
Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)
The Entecavir Continuous Treatment Cohort consisted of participants from study AI463-022 (NCT00035633) who were nucleoside-naive HBeAg-positive and enrolled in the current study with ≤35 days off treatment between the last dose in AI463-022 and the first dose in the current. This cohort is considered to be on continuous entecavir treatment and permitted assessment of continuous administration of entecavir in AI463-022 and the current study.
Measured: Baseline to Weeks 48, 96, 144, 192, and 240
Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)
The Entecavir Retreatment Cohort consisted of participants who were nucleoside-naive, HBeAg-negative and enrolled from BMS study AI463-027 with >60 days off treatment between the last dose in AI463-027 and the first dose in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as retreatment in the current study.
Measured: Baseline to Weeks 48, 96, and 144
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Measured: Baseline to Week 96
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
The Lamivudine Continuous Switch Cohort consisted of participants who were nucleoside-naive, HBeAg-positive and received lamivudine in BMS study AI463-022 (NCT00035633) and enrolled in the current study with ≤35 days off treatment between end of dosing in AI463-022 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Measured: Baseline to Week 144
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with >60 days between end of dosing in AI463-027 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Measured: Baseline to Week 96
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
The Lamivudine Retreatment Switch Cohort consisted of participants who were nucleoside-naive HBeAg negative and enrolled from BMS study AI463-027 (NCT00035789) with >60 days between end of dosing in AI463-027 and the switch to entecavir in the current study. This cohort permitted assessment of entecavir, 1.0 mg, provided as switch therapy in the current study.
Measured: Baseline to Week 144
Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)
The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR Assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing. ULN=upper limit of normal.
Measured: End of dosing to Weeks 48 and 96 off-treatment follow-up
Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)
The Amendment 11 Cohort consisted of participants who were HBeAg negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing.
Measured: End of dosing to Weeks 48 and 96 off-treatment follow-up

Timeline

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

Jan 2001Apr 2011

First posted22 Sep 2011 (estimated)
Study startJan 2001
Primary completionDec 2009
Study completionApr 2011

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis B VirusStudies 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 1,053 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01438424
Sponsor's protocol ID: AI463-901
Status last verified: Jul 2012
First submitted: 16 Sep 2011
Last updated: 23 Aug 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Manns MP, Akarca US, Chang TT, Sievert W, Yoon SK, Tsai N, Min A, Pangerl A, Beebe S, Yu M, Wongcharatrawee S. Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901. Expert Opin Drug Saf. 2012 May;11(3):361-8. doi: 10.1517/14740338.2012.653340. Epub 2012 Jan 11.
PubMed 22233350

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 Hepatitis B Virus trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Preliminary Assessment of Safety and Antiviral Activity of Open-label Entecavir in Subjects With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
ClinicalTrials.gov ID: NCT01438424
Acronym / sponsor ID: AI463-901
Conditions: Hepatitis B Virus, HBV
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,053 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: Jan 2001
Primary completion: Dec 2009 (actual)
Study completion: Apr 2011 (actual)
First posted: 22 Sep 2011 (estimated)
Results: Posted 23 Aug 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 provide entecavir to participants who have completed another entecavir trial without achieving virologic response or who relapsed during postdosing follow-up.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Entecavir, 1.0 mg, with or without lamivudine	Experimental	Drug: Entecavir, Drug: Lamivudine

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (13 listed)

Age of 16 years and older
Receipt of entecavir or lamivudine in a previous entecavir study.
Virologic nonresponders at Week 48
Partial virologic responders who became nonresponders during the second year of treatment
Partial virologic responders at Week 96

Key exclusion criteria (9 listed)

HIV coinfection
Receiving nephrotoxic or hepatotoxic agents
Ongoing opportunistic infections
Hemoglobin level <11.0 g/dL except for those enrolled from AI463-048
Platelet count <70,000 mm^3 except for those enrolled from AI463-048

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: BaracludeTablets, Oral, 1.0 mg, once daily	Drug	Entecavir, 1.0 mg, with or without lamivudine
LamivudineOral, 100 mg, daily	Drug	Entecavir, 1.0 mg, with or without lamivudine

Primary outcome

Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Time frame: Continuously from Day 1 through Week 240
An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment. An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine transaminase; ULN=upper limit of normal.
Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240
Time frame: Day 1 of treatment through Week 240
Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0; Gr 2=8.0-<9.5; Gr 3=6.5-<8.0; Gr 4=<6.5 White blood cells (cells/mm^3): Gr 1=2,500-<4,000; Gr 2=1,000-<2,500; Gr 3=800-<1,000; Gr 4=<800. Neutrophils (cells/mm^3): Gr 1=1000-<1500; Gr 2=750-<1000; Gr 3=500-<750; Gr 4=<500. Platelets (cells/mm^3): Gr 1=75,000-99,000; Gr 2=50,000-<75,000; Gr 3=20,000-<50,000; Gr 4=<20,000. Prothrombin time (seconds): Gr 1=1.01-<1.26*ULN; Gr 2=1.26-<1.51 *ULN; Gr 3=1.51-3*ULN; Gr 4=>3*ULN. INR: Gr 1=1.24-1.5; Gr 2=1.5-2; Gr 3=2-3; Gr 4=>3. INR=international normalized ratio; ULN=upper limit of normal. .
Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing
Time frame: Day 1 of treatment through Week 240
Amylase: Grade 1=1.10-<1.40*ULN; Grade 2=1.40-< 2.10*ULN; Grade 3=2.10-5.00*ULN; Grade 4=>5.00*ULN. Lipase: Grade 1.1-<1.4*ULN; Grade 2=1.4-<2.1*ULN; Grade 3=2.1-5.0*ULN; Grade 4=>5.0*ULN. Creatinine: Grade 1=1.10-< 1.60*ULN; Grade 2=1.60-<3.10*ULN; Grade 3=3.10-6.00*ULN; Grade 4=>6.00*ULN. Blood urea nitrogen (BUN): Grade 1=1.25-<2.60*ULN; Grade 2=2.60-<5.10*ULN; Grade 3=5.10-10*ULN; Grade 4=>10*ULN. ULN=upper limit of normal.
Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing
Time frame: Day 1 of treatment through Week 240
Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-<90; Gr 3=80-<85; Gr 4=40-<80. Hyperchloremia: Gr 1=113-<117; Gr 2=117-<121; Gr 3=121-125; Gr 4>125. Hypocarbia: Gr 1=19-21; Gr 2=15-<19; Gr 3=41-45; Gr 4=>45. Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=>45. Hyponatremia: Gr 1=130-132; Gr 2=123-<130; Gr 3=116-<123; Gr 4<116. Hypernatremia: Gr 1=148-<151; Gr 2=151-<158; Gr 3=158-165; Gr 4=>165. Hypokalemia: Gr 1=3-3.4; Gr 2=2.5-<3; Gr 3=2-<2.5; Gr 4=<2. Hyperkalemia: Gr 1=5.6-<6.1; G2=6.1-<6.6; Gr 3=6.6-7; Gr 4=>7. Hypoglycemia: Gr 1=55-64; Gr 2=40-<55; Gr 3=30-< 40; G4=-<30. Hyperglycemia: Gr 1=116-<161; Gr 2=161-<251; Gr 3=251-500; Gr 4>500.
Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
Time frame: Continuously from Day 1 through Week 144
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. AST=aspartate aminotransferase; ULN=upper limit of normal.
Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
Time frame: Continuously from Day 1 through Week 192
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine aminotransferase; ULN=upper limit of normal.
Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)
Time frame: End of dosing to Week 48 off-treatment follow-up
The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA <300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.

19 secondary outcomes

Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay
Time frame: Study entry to Week 192
Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay
Time frame: Study entry to Week 192
Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay
Time frame: Baseline to Week 192
Overall Study: Mean HBV DNA Level by PCR Assay
Time frame: Study entry to Week 216
Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)
Time frame: Study entry to Week 216
Overall Study: Percentage of Participants With HBeAg Seroconversion
Time frame: Study entry to Week 216
Overall Study: Mean Alanine Transaminase (ALT) Levels
Time frame: Study entry to Week 216
Overall Study: Percentage of Participants Who Achieved ALT Normalization
Time frame: Study entry to Week 216
Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)
Time frame: Baseline to Week 192
Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)
Time frame: Baseline to Week 192
Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay
Time frame: Baseline to Week 144
Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)
Time frame: Baseline to Weeks 48, 96, 144, 192, and 240
Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)
Time frame: Baseline to Weeks 48, 96, and 144
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
Time frame: Baseline to Week 96
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
Time frame: Baseline to Week 144
Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
Time frame: Baseline to Week 96
Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
Time frame: Baseline to Week 144
Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)
Time frame: End of dosing to Weeks 48 and 96 off-treatment follow-up
Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)
Time frame: End of dosing to Weeks 48 and 96 off-treatment follow-up

Results and safety

Results posted to the registry on 23 Aug 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine	1,051	634

Primary outcome: Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs

Time frame: Continuously from Day 1 through Week 240. Number. Unit: Participants

Measure	Entecavir, 0.5 or 1.0 mg QD, With or Without Lamivudine n = 1051
Deaths on treatment	18
Deaths off treatment	9
SAEs on treatment	169
Discontinuations due to AEs on treatment	14
Any AE on treatment	900
Grade 3 and 4 AEs on treatment	203
Malignancies on and off treatment	35
ALT flares (ALT>2entry and >10ULN) on treatment	32

Population analysed: All participants who received at least 1 dose of study drug in the current study.

Primary outcome: Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240

Time frame: Day 1 of treatment through Week 240. Number. Unit: Participants

Measure	Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine n = 1051
Hemoglobin (All grades) (n=1007)	49
White blood cells (All grades) (n=950)	226
Neutrophils (All grades) (n=1002)	109
Platelets (All grades) (n=979)	51
Protrombin time (All grades) (n=746)	226
INR (All grades)(n=746)	214
Hemoglobin (Grades 3-4) (n=1007)	2
White blood cells (Grades 3-4) (n=950)	1

Population analysed: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Primary outcome: Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing

Time frame: Day 1 of treatment through Week 240. Number. Unit: Participants

Measure	Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine n = 1051
Amylase (All grades) (n=875)	179
Lipase (All grades) (n=390)	126
Amylase (Grades 3-4) (n=875)	13
Lipase (Grades 3-4) (n=390)	38
BUN/Urea (All grades) (n=998)	57
Creatinine (All grades) (n=1000)	61
BUN/Urea (Grades 3-4) (n=998)	0
Creatinine (Grades 3-4) (n=1000)	2

Population analysed: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

Primary outcome: Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing

Time frame: Day 1 of treatment through Week 240. Number. Unit: Participants

Measure	Entecavir, 0.5 or 1.0 mg, With or Without Lamivudine n = 1051
Hypochloremia (mEq/L) (All grades) (n=982)	44
Hyperchloremia (mEq/L) (All grades) (n=982)	76
Hypocarbia (mEq/L) (All grades) (n=831)	285
Hypercarbia (mEq/L) (All grades) (n=831)	148
Hyponatremia (mEq/L) (All grades) (n=1003)	68
Hypernatremia (mEq/L) (All grades) (n=1003)	106
Hypokalemia (mEq/L) (All grades) (n=993)	135
Hyperkalemia (mEq/L) (All grades (n=993)	42

Population analysed: Participants who received at least 1 dose of study drug in the current study. (n=number of evaluable participants)

19 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, 10 mg	7 of 35 (20%)	27 of 35 (77.1%)	Not reported
Entecavir, 0.02588 mg	0 of 1 (0%)	0 of 1 (0%)	Not reported
Entecavir, 0.1 mg	3 of 29 (10.3%)	25 of 29 (86.2%)	Not reported
Entecavir, 0.5 mg	57 of 336 (17%)	274 of 336 (81.5%)	Not reported
Entecavir, 1.0 mg	15 of 123 (12.2%)	94 of 123 (76.4%)	Not reported
Lamovidine, 100 mg	87 of 523 (16.6%)	439 of 523 (83.9%)	Not reported
Missing	0 of 2 (0%)	2 of 2 (100%)	Not reported
Placebo	0 of 2 (0%)	1 of 2 (50%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22233350Manns MP, Akarca US, Chang TT, Sievert W, Yoon SK, Tsai N, Min A, Pangerl A, Beebe S, Yu M, Wongcharatrawee S. Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901. Expert Opin Drug Saf. 2012 May;11(3):361-8. doi: 10.1517/14740338.2012.653340. Epub 2012 Jan 11.

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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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Entecavir and Lamivudine in people with Hepatitis B Virus and HBV, run by Bristol-Myers Squibb.

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 13 inclusion and 9 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 23 Aug 2012. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 23 Aug 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?

Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs (time frame: Continuously from Day 1 through Week 240). The study lists 7 primary outcomes in all. 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 NCT01438424, which also lists 1 linked publication.

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 23 Aug 2012.