Trial Outcomes & Findings for A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection (NCT NCT00393484)
NCT ID: NCT00393484
Last Updated: 2014-11-26
Results Overview
Virologic response=Hepatitis B virus DNA \<300 copies/mL by polymerase chain reaction assay.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
122 participants
Primary outcome timeframe
At Week 24
Results posted on
2014-11-26
Participant Flow
A total of 122 participants were enrolled in this study; 2 did not receive treatment.
Participant milestones
| Measure |
Entecavir, 0.5 mg + Placebo
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Double-blind Period (Day 1 to Week 96)
STARTED
|
56
|
64
|
|
Double-blind Period (Day 1 to Week 96)
Participants Excluded From Analysis
|
1
|
1
|
|
Double-blind Period (Day 1 to Week 96)
COMPLETED
|
54
|
52
|
|
Double-blind Period (Day 1 to Week 96)
NOT COMPLETED
|
2
|
12
|
|
Open-label Period (Weeks 96 to 240)
STARTED
|
48
|
44
|
|
Open-label Period (Weeks 96 to 240)
Withdrew Consent
|
6
|
6
|
|
Open-label Period (Weeks 96 to 240)
Lack of Efficacy
|
0
|
2
|
|
Open-label Period (Weeks 96 to 240)
COMPLETED
|
40
|
21
|
|
Open-label Period (Weeks 96 to 240)
NOT COMPLETED
|
8
|
23
|
Reasons for withdrawal
| Measure |
Entecavir, 0.5 mg + Placebo
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Double-blind Period (Day 1 to Week 96)
Adverse Event
|
0
|
1
|
|
Double-blind Period (Day 1 to Week 96)
Withdrawal by Subject
|
2
|
0
|
|
Double-blind Period (Day 1 to Week 96)
No longer met inclusion criteria
|
0
|
3
|
|
Double-blind Period (Day 1 to Week 96)
Lack of Efficacy
|
0
|
6
|
|
Double-blind Period (Day 1 to Week 96)
Lost to Follow-up
|
0
|
2
|
|
Open-label Period (Weeks 96 to 240)
Withdrawal by Subject
|
4
|
1
|
|
Open-label Period (Weeks 96 to 240)
Death
|
1
|
0
|
|
Open-label Period (Weeks 96 to 240)
Lost to Follow-up
|
1
|
2
|
|
Open-label Period (Weeks 96 to 240)
Noncompliance
|
2
|
2
|
|
Open-label Period (Weeks 96 to 240)
Lack of Efficacy
|
0
|
18
|
Baseline Characteristics
A Study in Korea of Entecavir Versus Lamivudine in Adults With Chronic Hepatitis B Infection
Baseline characteristics by cohort
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.73 years
STANDARD_DEVIATION 11.93 • n=5 Participants
|
48.98 years
STANDARD_DEVIATION 7.84 • n=7 Participants
|
47.46 years
STANDARD_DEVIATION 10.05 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
56 participants
n=5 Participants
|
64 participants
n=7 Participants
|
120 participants
n=5 Participants
|
|
Prior interferon treatment status
No
|
54 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
|
Prior interferon treatment status
Yes
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Hepatitis B virus DNA by polymerase chain reaction
|
6.06 log10 copies/mL
STANDARD_DEVIATION 0.78 • n=5 Participants
|
5.79 log10 copies/mL
STANDARD_DEVIATION 0.90 • n=7 Participants
|
5.91 log10 copies/mL
STANDARD_DEVIATION 0.86 • n=5 Participants
|
|
Alanine aminotransferase
|
110.46 U/L
STANDARD_DEVIATION 81.97 • n=5 Participants
|
93.94 U/L
STANDARD_DEVIATION 58.46 • n=7 Participants
|
101.65 U/L
STANDARD_DEVIATION 70.59 • n=5 Participants
|
PRIMARY outcome
Timeframe: At Week 24Population: Randomized participants who received at least 1 dose of study drug
Virologic response=Hepatitis B virus DNA \<300 copies/mL by polymerase chain reaction assay.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Percentage of Participants Who Achieved a Virologic Response at Week 24
|
92.86 Percentage of participants
|
67.19 Percentage of participants
|
SECONDARY outcome
Timeframe: At Weeks 24, 48, and 96Population: Randomized participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
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
Week 24: HBV DNA <10^3
|
54 Participants
|
46 Participants
|
|
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
Week 24: HBV DNA <10^4
|
54 Participants
|
53 Participants
|
|
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
Week 24: HBV DNA <10^5
|
54 Participants
|
59 Participants
|
|
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
Week 48: HBV DNA <10^3
|
54 Participants
|
45 Participants
|
|
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
Week 48: HBV DNA <10^4
|
55 Participants
|
50 Participants
|
|
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
Week 48: HBV DNA <10^5
|
55 Participants
|
52 Participants
|
|
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
Week 96: HBV DNA <10^3
|
53 Participants
|
38 Participants
|
|
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
Week 96: HBV DNA <10^4
|
53 Participants
|
42 Participants
|
|
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
Week 96: HBV DNA <10^5
|
53 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: At Weeks 24, 48, 96, 144, 192, and 240Population: Randomized participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
At 24 Weeks
|
3.58 log10 copies/mL
Standard Deviation 0.60
|
2.95 log10 copies/mL
Standard Deviation 0.69
|
|
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
At 48 Weeks
|
3.56 log10 copies/mL
Standard Deviation 0.53
|
2.65 log10 copies/mL
Standard Deviation 0.61
|
|
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
At 96 Weeks
|
3.59 log10 copies/mL
Standard Deviation 0.52
|
2.42 log10 copies/mL
Standard Deviation 0.60
|
|
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
At 144 Weeks
|
-3.60 log10 copies/mL
Standard Deviation 0.60
|
-2.74 log10 copies/mL
Standard Deviation 0.70
|
|
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
At 192 Weeks
|
-3.60 log10 copies/mL
Standard Deviation 0.63
|
-2.75 log10 copies/mL
Standard Deviation 0.73
|
|
Mean Log10 Reduction From Baseline in Hepatitis B Virus (HBV) DNA at Weeks 24, 48, 96, 144, 192, and 240
At 240 Weeks
|
-3.53 log10 copies/mL
Standard Deviation 0.85
|
-2.69 log10 copies/mL
Standard Deviation 0.98
|
SECONDARY outcome
Timeframe: At Week 24Population: Randomized participants who received at least 1 dose of study drug
Mean ALT values from baseline by laboratory test. .
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Mean Laboratory Test Values for Alanine Aminotransferase (ALT) at Week 24
|
31.5 U/L
Standard Deviation 14.04
|
43.26 U/L
Standard Deviation 32.08
|
SECONDARY outcome
Timeframe: At Weeks 24, 48, and 96Population: Randomized participants who received at least 1 dose of study drug
Normalization of serum ALT= ≤\*institutional upper limit of normal.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
At 24 Weeks
|
43 Participants
|
37 Participants
|
|
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
At 48 Weeks
|
48 Participants
|
38 Participants
|
|
Number of Participants With Normalization of Serum Alanine Aminotransferase (ALT) Levels at Weeks 24, 48, and 96
At 96 Weeks
|
49 Participants
|
33 Participants
|
SECONDARY outcome
Timeframe: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up periodPopulation: Treated cohort: includes participants who are randomized and received at least 1 dose of study drug (ETV or LVD).
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.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
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
Deaths
|
0 Participants
|
0 Participants
|
|
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
SAEs
|
0 Participants
|
3 Participants
|
|
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
Discontinuations Due to AEs
|
0 Participants
|
1 Participants
|
|
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
Any AEs
|
14 Participants
|
23 Participants
|
|
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
Most common AEs: Upper Respiratory Infection
|
3 Participants
|
7 Participants
|
|
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
Most common AEs: Nasopharyngitis
|
1 Participants
|
4 Participants
|
|
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
Most common AEs: Urticaria
|
0 Participants
|
3 Participants
|
|
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
WHO Grade 3/4 AEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Start of dosing (Day 1) until end of treatment (24 weeks) + 5 days and to end of 24-week follow-up periodPopulation: Randomized participants who received at least 1 dose of study drug
ALT flares=ALT\>2\*Baseline and 10\*upper limit of normal. Serious adverse events/deaths reported for enrolled patients regardless of treatment status.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
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 elevations >2*Baseline (BL)
|
0 Participants
|
1 Participants
|
|
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
AST elevations >2*BL
|
0 Participants
|
1 Participants
|
|
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 elevations >3*BL & AST elevations >2*BL
|
0 Participants
|
1 Participants
|
|
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
Simultaneous ALT & Total bilirubin elevation
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to the end of the 24-week follow-up periodPopulation: Randomized participants who received at least 1 dose of study drug
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).
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
Gr 4 Prothrombin time (>3*ULN)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
Gr 3 Glucose (251-500 mg/dL)
|
1 Participants
|
2 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
Gr 3 ALT (5.1-10*ULN)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 24
Gr 3 Lipase (2.0-5.0*ULN)
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Start of dosing (Day 1) until end of treatment (Week 24) + 5 days and to end of 24-week follow-up periodPopulation: Randomized participants who received at least 1 dose of study drug
Vital signs assessed included blood pressure, heart rate, body temperature, and respiration rate.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Number of Participants With Clinically or Statistically Significant Changes in Vital Sign Measurements at Week 24
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Week 24Virologic 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).
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Number of Participants With Virologic Rebound at Week 24
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: At Weeks 48, 96, 144, 192, and 240Population: Randomized participants who received at least 1 dose of study drug
Undetectable HBV DNA= \<300 copies/mL by polymerase chain reaction assay
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
At 48 Weeks
|
94.64 Percetage of participants
|
60.94 Percetage of participants
|
|
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
At 96 Weeks
|
94.64 Percetage of participants
|
48.44 Percetage of participants
|
|
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
At 144 Weeks
|
67.86 Percetage of participants
|
34.38 Percetage of participants
|
|
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
At 192 Weeks
|
69.64 Percetage of participants
|
25.00 Percetage of participants
|
|
Percentage of Participants With a Virologic Response as Defined by Undetectable Hepatitis B Virus DNA at Weeks 48, 96, 144, 192, and 240
At 240 Weeks
|
67.86 Percetage of participants
|
15.63 Percetage of participants
|
SECONDARY outcome
Timeframe: At 96 weeksPopulation: All participants who received study drug and who had samples of measureable HBV DNA values
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).
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=55 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=61 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96
Viral rebound
|
1 Participants
|
26 Participants
|
|
Number of Participants With Viral Rebound and Drug-resistant Hepatitis B Virus (HBV) DNA Mutations at Week 96
Drug-resistant mutations
|
0 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: Start of dosing (Day 1) until end of treatment (Week 240) + 5 daysPopulation: Participants who were randomized and received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=56 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
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
SAEs
|
7 Participants
|
17 Participants
|
|
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
Discontinuations due to AEs
|
0 Participants
|
1 Participants
|
|
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
Any nonserious AEs
|
48 Participants
|
49 Participants
|
|
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
Nonserious AEs related to study conditions
|
1 Participants
|
6 Participants
|
|
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
SAEs related to study conditions
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Start of dosing (Day 1) until Week 96Population: Randomized participants who received at least 1 dose of study drug and who were evaluable.
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).
Outcome measures
| Measure |
Entecavir, 0.5 mg + Placebo
n=55 Participants
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=62 Participants
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
ALT
|
0 Participants
|
6 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Platelets
|
1 Participants
|
1 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Prothrombin time
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Neutrophils
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
AST
|
0 Participants
|
3 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Total bilirubiin
|
1 Participants
|
3 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Creatinine
|
2 Participants
|
0 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Lipase
|
2 Participants
|
4 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Potassium
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results by World Health Organization (WHO) Criteria at Week 96
Glucose, fasting
|
3 Participants
|
2 Participants
|
Adverse Events
Entecavir , 0.5 mg + Placebo
Serious events: 7 serious events
Other events: 28 other events
Deaths: 0 deaths
Lamivudine, 100 mg + Placebo
Serious events: 17 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Entecavir , 0.5 mg + Placebo
n=56 participants at risk
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 participants at risk
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liposarcoma recurrent
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Injury, poisoning and procedural complications
Subdural hemorrhage
|
3.6%
2/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Investigations
Blood glucose increased
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Hepatobiliary disorders
Gallbladder polyp
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Injury, poisoning and procedural complications
Rib fracture
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Musculoskeletal and connective tissue disorders
Tibia fracture
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Infections and infestations
Cellulitis
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumor benign
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Injury, poisoning and procedural complications
Cerebral vertebral fracture
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc herniation
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Investigations
Red blood cell count decreased
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chondrosarcoma
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
1.6%
1/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Nervous system disorders
Hydrocephalus
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Eye disorders
Optic neuropathy
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Nervous system disorders
Subarachnoid hemorrhage
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
0.00%
0/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
Other adverse events
| Measure |
Entecavir , 0.5 mg + Placebo
n=56 participants at risk
Participants received entecavir, 0.5 mg, once daily, with lamivudine placebo tablets, once daily, administered orally through Week 96 (double-blind period). Then, participants received entecavir, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
Lamivudine, 100 mg + Placebo
n=64 participants at risk
Participants received lamivudine, 100 mg, once daily, with entecavir placebo tablets, once daily, administered orally, through Week 96 (double-blind period). Then, participants received lamivudine, 0.5 mg, once daiy, administered orally for Weeks 96-240 (open-label period).
|
|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
16.1%
9/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
18.8%
12/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Infections and infestations
Nasopharyngitis
|
10.7%
6/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
9.4%
6/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
4.7%
3/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
General disorders
Fatigue
|
8.9%
5/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
9.4%
6/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Psychiatric disorders
Insomnia
|
3.6%
2/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
4.7%
3/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Investigations
Blood glucose increased
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
4.7%
3/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Gastrointestinal disorders
Reflux esophagitis
|
5.4%
3/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
3.1%
2/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis, contact
|
1.8%
1/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
4.7%
3/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Gastrointestinal disorders
Gastritis
|
8.9%
5/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
3.1%
2/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
4.7%
3/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.6%
2/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
4.7%
3/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
|
Gastrointestinal disorders
Dyspepsia
|
5.4%
3/56 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
3.1%
2/64 • Start of dosing (Day 1) until end of treatment (Week 240) + 5 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER