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A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Entecavir
Lamivudine Placebo
Lamivudine
Entecavir Placebo
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Entecavir + Lamivudine placebo (0-96 weeks) Entecavir (96-240 weeks)

Lamivudine + Entecavir placebo (0-96 weeks) Lamivudine (96-240 weeks)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24
Mean ALT values from baseline by laboratory test. .
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.
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.
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.
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).
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.
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).
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
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).
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.
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).

Full Information

First Posted
October 26, 2006
Last Updated
November 6, 2014
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00393484
Brief Title
A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

5. Study Description

Brief 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 B e antigen-negative chronic hepatitis B virus infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
122 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Entecavir + Lamivudine placebo (0-96 weeks) Entecavir (96-240 weeks)
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Lamivudine + Entecavir placebo (0-96 weeks) Lamivudine (96-240 weeks)
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude, BMS-200475
Intervention Description
Tablets, Oral, 0.5 mg, once daily (0-96 weeks) and (96-240 weeks)
Intervention Type
Drug
Intervention Name(s)
Lamivudine Placebo
Intervention Description
Capsules, Oral, 0 mg, once daily (0-96 weeks)
Intervention Type
Drug
Intervention Name(s)
Lamivudine
Intervention Description
Capsules, Oral, 100 mg, once daily (0-96 weeks) Tablets, Oral, 100 mg, once daily (96-240 weeks)
Intervention Type
Drug
Intervention Name(s)
Entecavir Placebo
Intervention Description
Tablets, Oral, 0 mg, once daily (0-96 weeks)
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved a Virologic Response at Week 24
Description
Virologic response=Hepatitis B virus DNA <300 copies/mL by polymerase chain reaction assay.
Time Frame
At Week 24
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
At Weeks 24, 48, and 96
Title
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
Description
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.
Time Frame
At Weeks 24, 48, 96, 144, 192, and 240
Title
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24
Description
Mean ALT values from baseline by laboratory test. .
Time Frame
At Week 24
Title
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
Description
Normalization of serum ALT= ≤*institutional upper limit of normal.
Time Frame
At Weeks 24, 48, and 96
Title
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
Description
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.
Time Frame
Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Title
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
Description
ALT flares=ALT>2*Baseline and 10*upper limit of normal. Serious adverse events/deaths reported for enrolled patients regardless of treatment status.
Time Frame
Start of dosing (Day 1) until end of treatment (24 weeks) + 5 days and to end of 24-week follow-up period
Title
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
Description
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).
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
Title
Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24
Description
Vital signs assessed included blood pressure, heart rate, body temperature, and respiration rate.
Time Frame
Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up period
Title
Number of Participants With Virologic Rebound at Week 24
Description
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).
Time Frame
At Week 24
Title
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
Description
Undetectable HBV DNA= <300 copies/mL by polymerase chain reaction assay
Time Frame
At Weeks 48, 96, 144, 192, and 240
Title
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96
Description
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).
Time Frame
At 96 weeks
Title
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
Description
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.
Time Frame
Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
Title
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Description
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).
Time Frame
Start of dosing (Day 1) until Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Bucheon
ZIP/Postal Code
420-717
Country
Korea, Republic of
Facility Name
Local Institution
City
Busan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Local Institution
City
Chuncheon
ZIP/Postal Code
200-704
Country
Korea, Republic of
Facility Name
Local Institution
City
Daegu
ZIP/Postal Code
700-721
Country
Korea, Republic of
Facility Name
Local Institution
City
Daegu
ZIP/Postal Code
705-030
Country
Korea, Republic of
Facility Name
Local Institution
City
Daejeon
ZIP/Postal Code
301-721
Country
Korea, Republic of
Facility Name
Local Institution
City
Guri
ZIP/Postal Code
471-020
Country
Korea, Republic of
Facility Name
Local Institution
City
Jeonju
ZIP/Postal Code
561-180
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
130-702
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
135-270
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
136-705
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
138-040
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
150-950
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
152-050
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection

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