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Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus (DEFINE)

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ClinicalTrials.gov Identifier: NCT00410202
Recruitment Status : Completed
First Posted : December 12, 2006
Results First Posted : July 4, 2012
Last Update Posted : November 21, 2013
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis B, Chronic
Interventions Drug: Entecavir
Drug: Tenofovir
Drug: Adefovir
Drug: Lamivudine
Enrollment 629
Recruitment Details A total of 629 participants were enrolled at 60 sites.
Pre-assignment Details Of the 629 participants enrolled, 416 were randomized (195 no longer met study criteria, 9 withdrew consent, and 9 had other reason). One participant randomized to entecavir + adefovir (ADV+LVD) Arm withdrew consent before treatment.
Arm/Group Title Entecavir + Adefovir (ETV+ADV) Combination Therapy Entecavir (ETV) Monotherapy Adefovir + Lamivudine (ADV+LVD) Combination Therapy
Hide Arm/Group Description ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees. ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks
Period Title: On-Treatment
Started 138 140 137
Discontinued Prior to Week 48 Visit 4 2 2
Discontinued at or After Week 48 Visit 2 6 3
Completed 63 [1] 61 [1] 66 [1]
Not Completed 75 79 71
Reason Not Completed
Continuing treatment             69             71             66
Adverse Event             1             3             2
Death             1             0             0
Lost to Follow-up             1             0             1
Lack of Efficacy             1             4             0
Withdrawal by Subject             2             1             1
Other Reason             0             0             1
[1]
Completed the 100 week dosing
Period Title: Off-treatment Follow up
Started 15 8 14
Completed 1 0 2
Not Completed 14 8 12
Reason Not Completed
Continuing off-treatment follow up             10             8             11
Follow up not required per protocol             3             0             1
Lost to Follow-up             1             0             0
Arm/Group Title Entecavir + Adefovir (ETV+ADV) Combination Therapy Entecavir (ETV) Monotherapy Adefovir + Lamivudine (ADV+LVD) Combination Therapy Total
Hide Arm/Group Description ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees. ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks Total of all reporting groups
Overall Number of Baseline Participants 138 140 137 415
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 138 participants 140 participants 137 participants 415 participants
46.0
(18 to 69)
43.5
(19 to 71)
43.0
(16 to 74)
45.0
(16 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Female
47
  34.1%
52
  37.1%
40
  29.2%
139
  33.5%
Male
91
  65.9%
88
  62.9%
97
  70.8%
276
  66.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Asian 132 131 126 389
White 6 9 11 26
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Australia 0 1 1 2
Canada 1 0 0 1
Hong Kong 5 7 5 17
India 4 3 5 12
Indonesia 0 1 0 1
Italy 1 0 0 1
Korea, Republic of 108 105 102 315
Malaysia 3 0 2 5
Philippines 0 1 1 2
Poland 5 9 9 23
Russian Federation 0 0 2 2
Singapore 1 1 0 2
Taiwan 8 9 9 26
Thailand 1 3 1 5
Turkey 1 0 0 1
Hepatitis B surface antigen (HBsAg) status at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Positive 138 140 137 415
Negative 0 0 0 0
Hepatitis B e antigen (HBeAg) status at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Positive 138 139 135 412
Negative 0 1 2 3
Hepatitis B e antibody (HBeAb) at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Positive 0 1 2 3
Negative 138 139 135 412
Alanine Aminotransferase (ALT)  
Median (Full Range)
Unit of measure:  U/L
Number Analyzed 138 participants 140 participants 137 participants 415 participants
49
(10 to 480)
50
(12 to 367)
45
(14 to 1300)
47
(10 to 1300)
LVD-Resistance Substitution   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 140 participants 137 participants 415 participants
Present 136 137 134 407
Absent 2 3 3 8
[1]
Measure Description: LVD resistance (LVDr) substitution at reverse transcription codon 204 (M240V/I/S). The participants who did not have LVDr substitution mutations at baseline (day 1) were distributed equally among the 3 study groups (2 with ETV+ADV combination therapy and 3 each with ETV monotherapy and ADV+LVD combination therapy).
log10 HBV DNA by PCR  
Median (Full Range)
Unit of measure:  IU/mL
Number Analyzed 138 participants 140 participants 137 participants 415 participants
7.6
(4.2 to 9.5)
7.5
(3.0 to 9.7)
7.6
(3.2 to 10.0)
7.6
(3.0 to 10.0)
International Normalization Ratio  
Median (Full Range)
Unit of measure:  Ratio
Number Analyzed 138 participants 140 participants 137 participants 415 participants
1.07
(0.80 to 1.97)
1.07
(0.87 to 2.48)
1.05
(0.82 to 7.24)
1.07
(0.80 to 7.24)
Albumin  
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 138 participants 140 participants 137 participants 415 participants
4.4
(3.1 to 5.1)
4.5
(3.5 to 5.1)
4.5
(3.5 to 5.1)
4.5
(3.1 to 5.1)
Total Bilirubin  
Median (Full Range)
Unit of measure:  mg/dL
Number Analyzed 138 participants 140 participants 137 participants 415 participants
0.6
(0.2 to 1.8)
0.6
(0.2 to 2.4)
0.6
(0.2 to 2.6)
0.6
(0.2 to 2.6)
1.Primary Outcome
Title Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
25.4 16.4 19.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1336
Comments [Not Specified]
Method Hochberg procedure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 8.9
Confidence Interval (2-Sided) 95%
-2.0 to 19.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2619
Comments [Not Specified]
Method Hochberg procedure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
-4.2 to 15.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. HBV DNA < 50 IU/mL = approximately 300 copies/mL. Percentage n/N: n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: Percentage of participants
43.5 39.3 28.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0095
Comments [Not Specified]
Method Hochberg procedure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference estimate
Estimated Value 15.0
Confidence Interval (2-Sided) 95%
3.7 to 26.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
25.4 13.6 16.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 11.8
Confidence Interval (2-Sided) 95%
2.5 to 21.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 8.6
Confidence Interval (2-Sided) 95%
-1.1 to 18.2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: Percentage of participants
38.4 36.4 25.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference estimate
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
1.8 to 23.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
20.3 11.4 11.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 8.9
Confidence Interval (2-Sided) 95%
0.3 to 17.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 8.6
Confidence Interval (2-Sided) 95%
-0.1 to 17.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest amount or concentration of analyte in a sample, which can be reliably detected, but not necessarily quantified.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
33.3 27.1 20.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference estimate
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
2.4 to 23.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With HBV DNA by PCR Category at Week 48
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
< LOQ (29 IU/mL) 25.4 13.6 16.8
LOQ to < 50 0 2.9 2.9
50 to < 172 8.0 2.9 5.8
172 to < 1,720 26.1 7.9 12.4
1,720 to < 17,200 28.3 22.1 31.4
17,200 to < 172,000 8.0 25.7 24.8
>= 172,000 0.7 23.6 4.4
Missing 3.6 1.4 1.5
8.Secondary Outcome
Title Percentage of Participants With HBV DNA by PCR Category at Week 96
Hide Description HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy were analyzed.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
< LOQ (29 IU/mL) 38.4 36.4 25.5
LOQ to < 50 5.1 2.9 2.9
50 to < 172 10.1 3.6 5.8
172 to < 1,720 15.2 6.4 18.2
1,720 to < 17,200 20.3 10.0 24.8
17,200 to < 172,000 5.8 15.7 13.9
>= 172,000 0 16.4 2.9
Missing 5.1 8.6 5.8
9.Secondary Outcome
Title Change in Mean log10 From Baseline in HBV DNA at Week 48
Hide Description HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load, negative values means reduction.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and had both baseline and post-baseline values. n=participants with baseline and Week 48 values.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 133 138 135
Mean (Standard Error)
Unit of Measure: log10 (IU/mL
HBV DNA at Week 48 2.79  (0.093) 4.01  (0.128) 3.36  (0.111)
Change from baseline -4.65  (0.077) -3.35  (0.117) -4.11  (0.108)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -1.26
Confidence Interval (2-Sided) 95%
-1.534 to -0.994
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV Monotherapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -0.55
Confidence Interval (2-Sided) 95%
-0.824 to -0.281
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in Mean log10 From Baseline in HBV DNA at Week 96
Hide Description HBV DNA was analyzed by PCR, using the Roche COBAS® TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and had both baseline and post-baseline values were analyzed. n= participants with baseline and Week 96 values.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 131 128 129
Mean (Standard Error)
Unit of Measure: participants
-5.06  (0.090) -4.17  (0.163) -4.49  (0.116)
11.Secondary Outcome
Title Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48
Hide Description ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 or 48 U/L.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and had ALT > 1 x ULN at baseline (day 1). Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator’s discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 78 82 69
Measure Type: Number
Unit of Measure: percentage of participants
75.6 78.0 76.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-15.5 to 10.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-15.0 to 12.6
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96
Hide Description ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 U/L.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and had ALT > 1 x ULN at baseline (day 1) were analyzed. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 78 82 69
Measure Type: Number
Unit of Measure: percentage of participants
76.9 74.4 79.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-16.2 to 10.6
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)
Hide Description HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 139 135
Measure Type: Number
Unit of Measure: percentage of participants
7.2 6.5 5.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-5.2 to 6.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-4.6 to 7.2
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)
Hide Description HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
12.3 10.7 13.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-9.5 to 6.4
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)
Hide Description HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 139 135
Measure Type: Number
Unit of Measure: percentage of participants
5.1 2.9 3.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-2.4 to 6.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-3.5 to 6.2
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)
Hide Description HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
7.2 3.6 5.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-3.6 to 7.8
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Hide Description HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator’s discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
0.7 0 0.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.7 to 2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-2.0 to 2.0
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96
Hide Description HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0
19.Secondary Outcome
Title Percentage of Participants With HBsAg Seroconversion at Week 48
Hide Description HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator’s discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
0.7 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ETV Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.7 to 2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ETV+ADV Combination Therapy, ADV+LVD Combination Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference Estimate
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.7 to 2.1
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Percentage of Participants With HBsAg Seroconversion at Week 96
Hide Description HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator’s discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0
21.Secondary Outcome
Title Cumulative Probability of Emergent Genotypic Resistance at Year 1
Hide Description yr=year. Cumulative probability (CP): Ptotal=1-(1-Pyr1)*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An "event" is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).
Time Frame Year 1
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants who were tested for resistance, ie. met the following selection criteria. 1) participants with HBV DNA ≥ 50 IU/mL at Week 48 or at the last on-treatment visit and 2) who developed VBT . n=participants
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 139 137
Measure Type: Number
Unit of Measure: percentage of participants
ETVr : n=134, 134, 134 0 3 0.7
ADVr /TDFr : n=137, 137, 135 0.7 0.7 1.5
ETVr or TDFr/ADVr : n=133, 132, 132 0.8 3.8 2.3
ETVr and TDFr/ADVr : n=138, 139, 137 0 0 0
ETVr with VBT: n=134, 134, 134 0 0.7 0
ADVr /TDFr with VBT: n=137, 137, 135 0 0 0
ETVr or ADVr/TDFr with VBT: n=133, 132, 132 0 0.8 0
ETVr and ADVr/TDFr with VBT: n=138, 139, 137 0 0 0
22.Secondary Outcome
Title Cumulative Probability of Emergent Genotypic Resistance at Year 2
Hide Description Cumulative probability (CP): Ptotal=1-(1-Pyr1)*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An "event" is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).
Time Frame Year 2
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants who were tested for resistance were analyzed, ie. They met the following selection criteria: 1) participants with HBV DNA ≥ 50 IU/mL at Week 96 or at the last on-treatment visit and 2) who developed VBT. n=participants
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 134 137 135
Measure Type: Number
Unit of Measure: percentage of participants
ETVr : n=130, 128, 131 0.8 9.8 1.5
ADVr/TDFr : n=132, 134, 131 0.7 1.5 2.2
ETVr or ADVr/TDFr : n=128, 125, 127 1.5 10.7 3.8
ETVr and ADVr/TDFr : n=134, 137, 135 0 0.7 0
ETVr with VBT: n=130, 128, 131 0 6.2 0
ADVr/TDFr with VBT: n=132, 134, 131 0 0.7 0
ETVr or ADVr/TDFr with VBT: n=128, 125, 127 0 6.3 0
ETVr and ADVr/TDFr with VBT: n=134, 137, 135 0 0.7 0
23.Secondary Outcome
Title Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Hide Description AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. Grade 1 = mild, Grade 2= moderate, Grade 3 = severe, Grade 4 = life threatening/disabling, Grade 5 = death.
Time Frame From start of study therapy through Week 100 + 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; QD for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator’s discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: participants
Deaths 0 0 1
SAEs 11 17 12
Discontinuations due to AEs 1 2 2
AEs 101 109 92
Grade 2-4 Related AEs 2 12 1
Grade 3-4 Related AEs 5 7 9
24.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities: Hematology
Hide Description Criteria for hematology abnormalities were: Hemoglobin: <=11.0 g/dL; White Blood Cells: <4000/mm^3; Absolute Neutrophils (includes absolute bands): <1500/mm^3; Platelets: <=99,000/mm^3; International Normalized Ratio: ≥ 1.5 and ≥ 0.5 from baseline.
Time Frame From start of study through Week 100 + 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; QD for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator’s discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: participants
Hemoglobin 8 9 11
White Blood Cells 53 48 38
Neutrophils 14 17 15
Platelets 13 14 12
International Normalized Ratio 8 7 9
25.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hide Description ULN=upper limit of normal (Normal ranges are Central lab data and vary according to the site). ALT:>1.25*ULN, AST:>1.25*ULN, ALP:>1.25*ULN, Total Bilirubin:>1.1*ULN, Serum Lipase:>1.10*ULN, Creatinine:>1.1*ULN, Blood Urea Nitrogen:1.25*ULN, Hyperglycemia:>116 mg/dL, Hypoglycemia:<64 mg/dL, Hyponatremia:<132meq/L, Hypokalemia:<3.4 meq/L, Albumin:≥1g/dL decrease from baseline, <3 g/dL; Hypernatremia:>148 meq/L, Hyperkalemia:>5.6 meq/L, Hypokalemia:<3.4 meq/L, Hyperchloremia:>113 meq/L, Hypochloremia:<93 meq/L; ALT flare: on treatment (OT), >2*Baseline and >10*ULN; off treatment (OF), 2*end of dosing value and >10*ULN
Time Frame On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants. n = number of participants in the OF period.
Arm/Group Title ETV+ADV Combination Therapy ETV Monotherapy ADV+LVD Combination Therapy
Hide Arm/Group Description:
ETV 1.0 mg + ADV 10 mg; QD for 100 weeks
ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
ADV 10 mg + LVD 100 mg; QD for 100 weeks
Overall Number of Participants Analyzed 138 140 137
Measure Type: Number
Unit of Measure: participants
Alanine aminotransferase (ALT) 76 83 74
Aspartate aminotransferase (AST) 60 62 53
Alkaline Phosphatase (ALP) 8 4 6
Albumin 1 1 1
Serum Lipase 24 33 24
Creatinine 2 2 4
Blood Urea Nitrogen 0 1 2
Hyperglycemia 39 46 37
Hypoglycemia 9 5 9
Hypernatremia 10 10 10
Hyponatremia 0 0 0
Hyperkalemia 3 4 5
Hypokalemia 4 2 2
Hyperchloremia 1 1 1
Hypochloremia 1 0 0
ALT flare - Ontreatment 3 2 2
ALT flare - Offtreatment 0 0 0
Time Frame Up to Week 96
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ADV + LVD Combination Therapy ETV Monotherapy ETV + ADV Combination Therapy
Hide Arm/Group Description ADV 10 mg + LVD 100 mg; QD for 100 weeks ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees. ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
All-Cause Mortality
ADV + LVD Combination Therapy ETV Monotherapy ETV + ADV Combination Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ADV + LVD Combination Therapy ETV Monotherapy ETV + ADV Combination Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/137 (9.49%)   21/140 (15.00%)   14/138 (10.14%) 
Congenital, familial and genetic disorders       
Congenital cystic kidney disease  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
Eye disorders       
Optic atrophy  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Gastrointestinal disorders       
Oesophageal varices haemorrhage  1  1/137 (0.73%)  1/140 (0.71%)  0/138 (0.00%) 
Melaena  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Haemorrhoids  1  0/137 (0.00%)  3/140 (2.14%)  1/138 (0.72%) 
Anal fistula  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Erosive oesophagitis  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
General disorders       
Asthenia  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Pyrexia  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Fatigue  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Hyperbilirubinaemia  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Infections and infestations       
Pelvic infection  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
Appendicitis  1  0/137 (0.00%)  2/140 (1.43%)  1/138 (0.72%) 
Hepatitis B  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Meningitis tuberculous  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Tonsillitis  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Injury, poisoning and procedural complications       
Ligament sprain  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Lower limb fracture  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Tibia fracture  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Wrist fracture  1  1/137 (0.73%)  1/140 (0.71%)  1/138 (0.72%) 
Facial bones fracture  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
Road traffic accident  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Limb crushing injury  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Muscle strain  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
Concussion  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion  1  1/137 (0.73%)  0/140 (0.00%)  2/138 (1.45%) 
Spondylolisthesis  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Plasmacytoma  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Hepatic neoplasm malignant  1  2/137 (1.46%)  5/140 (3.57%)  4/138 (2.90%) 
Colon adenoma  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Fibroadenoma of breast  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Nervous system disorders       
Intracranial hypotension  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Dizziness  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Hydrocephalus  1  1/137 (0.73%)  1/140 (0.71%)  0/138 (0.00%) 
Psychiatric disorders       
Suicide attempt  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
Renal and urinary disorders       
Ureteric stenosis  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Calculus ureteric  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  0/137 (0.00%)  0/140 (0.00%)  1/138 (0.72%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Vascular disorders       
Hot flush  1  1/137 (0.73%)  0/140 (0.00%)  0/138 (0.00%) 
Aneurysm ruptured  1  0/137 (0.00%)  1/140 (0.71%)  0/138 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ADV + LVD Combination Therapy ETV Monotherapy ETV + ADV Combination Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   62/137 (45.26%)   75/140 (53.57%)   63/138 (45.65%) 
Gastrointestinal disorders       
Abdominal pain upper  1  6/137 (4.38%)  10/140 (7.14%)  5/138 (3.62%) 
Abdominal discomfort  1  7/137 (5.11%)  3/140 (2.14%)  8/138 (5.80%) 
Nausea  1  4/137 (2.92%)  8/140 (5.71%)  6/138 (4.35%) 
Dyspepsia  1  8/137 (5.84%)  6/140 (4.29%)  10/138 (7.25%) 
General disorders       
Fatigue  1  8/137 (5.84%)  4/140 (2.86%)  4/138 (2.90%) 
Hepatobiliary disorders       
Hepatic steatosis  1  9/137 (6.57%)  8/140 (5.71%)  4/138 (2.90%) 
Infections and infestations       
Upper respiratory tract infection  1  19/137 (13.87%)  28/140 (20.00%)  23/138 (16.67%) 
Nasopharyngitis  1  8/137 (5.84%)  17/140 (12.14%)  17/138 (12.32%) 
Investigations       
Aspartate aminotransferase increased  1  1/137 (0.73%)  7/140 (5.00%)  5/138 (3.62%) 
Alanine aminotransferase increased  1  5/137 (3.65%)  8/140 (5.71%)  8/138 (5.80%) 
Nervous system disorders       
Headache  1  13/137 (9.49%)  5/140 (3.57%)  8/138 (5.80%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  7/137 (5.11%)  5/140 (3.57%)  2/138 (1.45%) 
Vascular disorders       
Hypertension  1  3/137 (2.19%)  7/140 (5.00%)  2/138 (1.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00410202     History of Changes
Other Study ID Numbers: AI463-111
First Submitted: December 11, 2006
First Posted: December 12, 2006
Results First Submitted: April 24, 2012
Results First Posted: July 4, 2012
Last Update Posted: November 21, 2013