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

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ClinicalTrials.gov Identifier: NCT00393484
Recruitment Status : Completed
First Posted : October 27, 2006
Results First Posted : November 18, 2010
Last Update Posted : November 26, 2014
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: Entecavir Drug: Lamivudine Placebo Drug: Lamivudine Drug: Entecavir Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : February 2007
Actual Primary Completion Date : January 2009
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A

Entecavir + Lamivudine placebo (0-96 weeks)

Entecavir (96-240 weeks)

Drug: Entecavir
Tablets, Oral, 0.5 mg, once daily (0-96 weeks) and (96-240 weeks)
Other Names:
  • Baraclude
  • BMS-200475

Drug: Lamivudine Placebo
Capsules, Oral, 0 mg, once daily (0-96 weeks)

Active Comparator: Arm B

Lamivudine + Entecavir placebo (0-96 weeks)

Lamivudine (96-240 weeks)

Drug: Lamivudine

Capsules, Oral, 100 mg, once daily (0-96 weeks)

Tablets, Oral, 100 mg, once daily (96-240 weeks)


Drug: Entecavir Placebo
Tablets, Oral, 0 mg, once daily (0-96 weeks)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 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.

  3. Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24 [ Time Frame: At Week 24 ]
    Mean ALT values from baseline by laboratory test. .

  4. 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 ]
    Normalization of serum ALT= ≤*institutional upper limit of normal.

  5. 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 ]
    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.

  6. 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 ]
    ALT flares=ALT>2*Baseline and 10*upper limit of normal. Serious adverse events/deaths reported for enrolled patients regardless of treatment status.

  7. 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 ]
    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).

  8. 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 ]
    Vital signs assessed included blood pressure, heart rate, body temperature, and respiration rate.

  9. Number of Participants With Virologic Rebound at Week 24 [ Time Frame: 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).

  10. 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 ]
    Undetectable HBV DNA= <300 copies/mL by polymerase chain reaction assay

  11. Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 [ Time Frame: At 96 weeks ]
    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).

  12. 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 ]
    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.

  13. 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 ]
    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).



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00393484


Locations
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Korea, Republic of
Local Institution
Bucheon, Korea, Republic of, 420-717
Local Institution
Busan, Korea, Republic of, 602-739
Local Institution
Chuncheon, Korea, Republic of, 200-704
Local Institution
Daegu, Korea, Republic of, 700-721
Local Institution
Daegu, Korea, Republic of, 705-030
Local Institution
Daejeon, Korea, Republic of, 301-721
Local Institution
Guri, Korea, Republic of, 471-020
Local Institution
Jeonju, Korea, Republic of, 561-180
Local Institution
Seoul, Korea, Republic of, 130-702
Local Institution
Seoul, Korea, Republic of, 135-270
Local Institution
Seoul, Korea, Republic of, 135-710
Local Institution
Seoul, Korea, Republic of, 136-705
Local Institution
Seoul, Korea, Republic of, 138-040
Local Institution
Seoul, Korea, Republic of, 150-950
Local Institution
Seoul, Korea, Republic of, 152-050
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00393484     History of Changes
Other Study ID Numbers: AI463-105
First Posted: October 27, 2006    Key Record Dates
Results First Posted: November 18, 2010
Last Update Posted: November 26, 2014
Last Verified: November 2014
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Lamivudine
Entecavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents