A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT00393484
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 122
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Lamivudine Placebo Entecavir + Lamivudine placebo (0-96 weeks) Entecavir (96-240 weeks) Arm B Entecavir Placebo Lamivudine + Entecavir placebo (0-96 weeks) Lamivudine (96-240 weeks) Arm A Entecavir Entecavir + Lamivudine placebo (0-96 weeks) Entecavir (96-240 weeks) Arm B Lamivudine Lamivudine + Entecavir placebo (0-96 weeks) Lamivudine (96-240 weeks)
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved a Virologic Response at Week 24 At Week 24 Virologic response=Hepatitis B virus DNA \<300 copies/mL by polymerase chain reaction assay.
- Secondary Outcome Measures
Name Time Method 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 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.
Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24 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.
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240 At Weeks 48, 96, 144, 192, and 240 Undetectable HBV DNA= \<300 copies/mL by polymerase chain reaction assay
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240 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.
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 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.
Number of Participants With Virologic Rebound at Week 24 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).
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24 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 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 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.
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24 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).
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96 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).
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96 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).
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 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.
Trial Locations
- Locations (1)
Local Institution
🇰🇷Seoul, Korea, Republic of