Trial Outcomes & Findings for Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus (NCT NCT00410202)
NCT ID: NCT00410202
Last Updated: 2013-11-21
Results Overview
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.
COMPLETED
PHASE3
629 participants
Week 48
2013-11-21
Participant Flow
A total of 629 participants were enrolled at 60 sites.
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.
Participant milestones
| Measure |
Entecavir + Adefovir (ETV+ADV) Combination Therapy
ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks
|
Entecavir (ETV) Monotherapy
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.
|
Adefovir + Lamivudine (ADV+LVD) Combination Therapy
ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks
|
|---|---|---|---|
|
On-Treatment
NOT COMPLETED
|
75
|
79
|
71
|
|
On-Treatment
STARTED
|
138
|
140
|
137
|
|
On-Treatment
Discontinued Prior to Week 48 Visit
|
4
|
2
|
2
|
|
On-Treatment
Discontinued at or After Week 48 Visit
|
2
|
6
|
3
|
|
On-Treatment
COMPLETED
|
63
|
61
|
66
|
|
Off-treatment Follow up
STARTED
|
15
|
8
|
14
|
|
Off-treatment Follow up
COMPLETED
|
1
|
0
|
2
|
|
Off-treatment Follow up
NOT COMPLETED
|
14
|
8
|
12
|
Reasons for withdrawal
| Measure |
Entecavir + Adefovir (ETV+ADV) Combination Therapy
ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks
|
Entecavir (ETV) Monotherapy
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.
|
Adefovir + Lamivudine (ADV+LVD) Combination Therapy
ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks
|
|---|---|---|---|
|
On-Treatment
Continuing treatment
|
69
|
71
|
66
|
|
On-Treatment
Adverse Event
|
1
|
3
|
2
|
|
On-Treatment
Death
|
1
|
0
|
0
|
|
On-Treatment
Lost to Follow-up
|
1
|
0
|
1
|
|
On-Treatment
Lack of Efficacy
|
1
|
4
|
0
|
|
On-Treatment
Withdrawal by Subject
|
2
|
1
|
1
|
|
On-Treatment
Other Reason
|
0
|
0
|
1
|
|
Off-treatment Follow up
Continuing off-treatment follow up
|
10
|
8
|
11
|
|
Off-treatment Follow up
Follow up not required per protocol
|
3
|
0
|
1
|
|
Off-treatment Follow up
Lost to Follow-up
|
1
|
0
|
0
|
Baseline Characteristics
Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus
Baseline characteristics by cohort
| Measure |
Entecavir + Adefovir (ETV+ADV) Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks
|
Entecavir (ETV) Monotherapy
n=140 Participants
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.
|
Adefovir + Lamivudine (ADV+LVD) Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks
|
Total
n=415 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
46.0 years
n=5 Participants
|
43.5 years
n=7 Participants
|
43.0 years
n=5 Participants
|
45.0 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
139 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
91 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
97 Participants
n=5 Participants
|
276 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
132 participants
n=5 Participants
|
131 participants
n=7 Participants
|
126 participants
n=5 Participants
|
389 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
6 participants
n=5 Participants
|
9 participants
n=7 Participants
|
11 participants
n=5 Participants
|
26 participants
n=4 Participants
|
|
Region of Enrollment
Australia
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
Hong Kong
|
5 participants
n=5 Participants
|
7 participants
n=7 Participants
|
5 participants
n=5 Participants
|
17 participants
n=4 Participants
|
|
Region of Enrollment
India
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Region of Enrollment
Indonesia
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
Korea, Republic of
|
108 participants
n=5 Participants
|
105 participants
n=7 Participants
|
102 participants
n=5 Participants
|
315 participants
n=4 Participants
|
|
Region of Enrollment
Malaysia
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
Philippines
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
5 participants
n=5 Participants
|
9 participants
n=7 Participants
|
9 participants
n=5 Participants
|
23 participants
n=4 Participants
|
|
Region of Enrollment
Russian Federation
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Singapore
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Taiwan
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
9 participants
n=5 Participants
|
26 participants
n=4 Participants
|
|
Region of Enrollment
Thailand
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
Turkey
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Hepatitis B surface antigen (HBsAg) status at baseline
Positive
|
138 participants
n=5 Participants
|
140 participants
n=7 Participants
|
137 participants
n=5 Participants
|
415 participants
n=4 Participants
|
|
Hepatitis B surface antigen (HBsAg) status at baseline
Negative
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
Hepatitis B e antigen (HBeAg) status at baseline
Positive
|
138 participants
n=5 Participants
|
139 participants
n=7 Participants
|
135 participants
n=5 Participants
|
412 participants
n=4 Participants
|
|
Hepatitis B e antigen (HBeAg) status at baseline
Negative
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Hepatitis B e antibody (HBeAb) at baseline
Positive
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Hepatitis B e antibody (HBeAb) at baseline
Negative
|
138 participants
n=5 Participants
|
139 participants
n=7 Participants
|
135 participants
n=5 Participants
|
412 participants
n=4 Participants
|
|
Alanine Aminotransferase (ALT)
|
49 U/L
n=5 Participants
|
50 U/L
n=7 Participants
|
45 U/L
n=5 Participants
|
47 U/L
n=4 Participants
|
|
LVD-Resistance Substitution
Present
|
136 participants
n=5 Participants
|
137 participants
n=7 Participants
|
134 participants
n=5 Participants
|
407 participants
n=4 Participants
|
|
LVD-Resistance Substitution
Absent
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
8 participants
n=4 Participants
|
|
log10 HBV DNA by PCR
|
7.6 IU/mL
n=5 Participants
|
7.5 IU/mL
n=7 Participants
|
7.6 IU/mL
n=5 Participants
|
7.6 IU/mL
n=4 Participants
|
|
International Normalization Ratio
|
1.07 ratio
n=5 Participants
|
1.07 ratio
n=7 Participants
|
1.05 ratio
n=5 Participants
|
1.07 ratio
n=4 Participants
|
|
Albumin
|
4.4 g/dL
n=5 Participants
|
4.5 g/dL
n=7 Participants
|
4.5 g/dL
n=5 Participants
|
4.5 g/dL
n=4 Participants
|
|
Total Bilirubin
|
0.6 mg/dL
n=5 Participants
|
0.6 mg/dL
n=7 Participants
|
0.6 mg/dL
n=5 Participants
|
0.6 mg/dL
n=4 Participants
|
PRIMARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
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
|
25.4 percentage of participants
|
16.4 percentage of participants
|
19.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96
|
43.5 Percentage of participants
|
39.3 Percentage of participants
|
28.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
|
25.4 percentage of participants
|
13.6 percentage of participants
|
16.8 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96
|
38.4 Percentage of participants
|
36.4 Percentage of participants
|
25.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48
|
20.3 percentage of participants
|
11.4 percentage of participants
|
11.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96
|
33.3 percentage of participants
|
27.1 percentage of participants
|
20.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy.
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
< LOQ (29 IU/mL)
|
25.4 percentage of participants
|
13.6 percentage of participants
|
16.8 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
LOQ to < 50
|
0 percentage of participants
|
2.9 percentage of participants
|
2.9 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
50 to < 172
|
8.0 percentage of participants
|
2.9 percentage of participants
|
5.8 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
172 to < 1,720
|
26.1 percentage of participants
|
7.9 percentage of participants
|
12.4 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
1,720 to < 17,200
|
28.3 percentage of participants
|
22.1 percentage of participants
|
31.4 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
17,200 to < 172,000
|
8.0 percentage of participants
|
25.7 percentage of participants
|
24.8 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
>= 172,000
|
0.7 percentage of participants
|
23.6 percentage of participants
|
4.4 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 48
Missing
|
3.6 percentage of participants
|
1.4 percentage of participants
|
1.5 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy were analyzed.
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
Missing
|
5.1 percentage of participants
|
8.6 percentage of participants
|
5.8 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
< LOQ (29 IU/mL)
|
38.4 percentage of participants
|
36.4 percentage of participants
|
25.5 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
LOQ to < 50
|
5.1 percentage of participants
|
2.9 percentage of participants
|
2.9 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
50 to < 172
|
10.1 percentage of participants
|
3.6 percentage of participants
|
5.8 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
172 to < 1,720
|
15.2 percentage of participants
|
6.4 percentage of participants
|
18.2 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
1,720 to < 17,200
|
20.3 percentage of participants
|
10.0 percentage of participants
|
24.8 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
17,200 to < 172,000
|
5.8 percentage of participants
|
15.7 percentage of participants
|
13.9 percentage of participants
|
|
Percentage of Participants With HBV DNA by PCR Category at Week 96
>= 172,000
|
0 percentage of participants
|
16.4 percentage of participants
|
2.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: 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.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=133 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=138 Participants
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+LVD Combination Therapy
n=135 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Change in Mean log10 From Baseline in HBV DNA at Week 48
HBV DNA at Week 48
|
2.79 log10 (IU/mL
Standard Error 0.093
|
4.01 log10 (IU/mL
Standard Error 0.128
|
3.36 log10 (IU/mL
Standard Error 0.111
|
|
Change in Mean log10 From Baseline in HBV DNA at Week 48
Change from baseline
|
-4.65 log10 (IU/mL
Standard Error 0.077
|
-3.35 log10 (IU/mL
Standard Error 0.117
|
-4.11 log10 (IU/mL
Standard Error 0.108
|
SECONDARY outcome
Timeframe: Baseline, Week 96Population: 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.
HBV DNA was analyzed by PCR, using the Roche COBAS® TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=131 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=128 Participants
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+LVD Combination Therapy
n=129 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Change in Mean log10 From Baseline in HBV DNA at Week 96
|
-5.06 participants
Standard Error 0.090
|
-4.17 participants
Standard Error 0.163
|
-4.49 participants
Standard Error 0.116
|
SECONDARY outcome
Timeframe: Week 48Population: 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.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=78 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=82 Participants
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+LVD Combination Therapy
n=69 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48
|
75.6 percentage of participants
|
78.0 percentage of participants
|
76.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 96Population: 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.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=78 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=82 Participants
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+LVD Combination Therapy
n=69 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96
|
76.9 percentage of participants
|
74.4 percentage of participants
|
79.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=139 Participants
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+LVD Combination Therapy
n=135 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)
|
7.2 percentage of participants
|
6.5 percentage of participants
|
5.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)
|
12.3 percentage of participants
|
10.7 percentage of participants
|
13.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
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).
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=139 Participants
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+LVD Combination Therapy
n=135 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)
|
5.1 percentage of participants
|
2.9 percentage of participants
|
3.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
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).
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)
|
7.2 percentage of participants
|
3.6 percentage of participants
|
5.1 percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
|
0.7 percentage of participants
|
0 percentage of participants
|
0.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBsAg Seroconversion at Week 48
|
0.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 96Population: Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Percentage of Participants With HBsAg Seroconversion at Week 96
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Year 1Population: 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
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).
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=139 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ETVr : n=134, 134, 134
|
0 percentage of participants
|
3 percentage of participants
|
0.7 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ADVr /TDFr : n=137, 137, 135
|
0.7 percentage of participants
|
0.7 percentage of participants
|
1.5 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ETVr or TDFr/ADVr : n=133, 132, 132
|
0.8 percentage of participants
|
3.8 percentage of participants
|
2.3 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ETVr and TDFr/ADVr : n=138, 139, 137
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ETVr with VBT: n=134, 134, 134
|
0 percentage of participants
|
0.7 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ADVr /TDFr with VBT: n=137, 137, 135
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ETVr or ADVr/TDFr with VBT: n=133, 132, 132
|
0 percentage of participants
|
0.8 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 1
ETVr and ADVr/TDFr with VBT: n=138, 139, 137
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Year 2Population: 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
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).
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=134 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=137 Participants
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+LVD Combination Therapy
n=135 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ETVr : n=130, 128, 131
|
0.8 percentage of participants
|
9.8 percentage of participants
|
1.5 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ADVr/TDFr : n=132, 134, 131
|
0.7 percentage of participants
|
1.5 percentage of participants
|
2.2 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ETVr or ADVr/TDFr : n=128, 125, 127
|
1.5 percentage of participants
|
10.7 percentage of participants
|
3.8 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ETVr and ADVr/TDFr : n=134, 137, 135
|
0 percentage of participants
|
0.7 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ETVr with VBT: n=130, 128, 131
|
0 percentage of participants
|
6.2 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ADVr/TDFr with VBT: n=132, 134, 131
|
0 percentage of participants
|
0.7 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ETVr or ADVr/TDFr with VBT: n=128, 125, 127
|
0 percentage of participants
|
6.3 percentage of participants
|
0 percentage of participants
|
|
Cumulative Probability of Emergent Genotypic Resistance at Year 2
ETVr and ADVr/TDFr with VBT: n=134, 137, 135
|
0 percentage of participants
|
0.7 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From start of study therapy through Week 100 + 5 daysPopulation: All treated participants.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Deaths
|
0 participants
|
0 participants
|
1 participants
|
|
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
SAEs
|
11 participants
|
17 participants
|
12 participants
|
|
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Discontinuations due to AEs
|
1 participants
|
2 participants
|
2 participants
|
|
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
AEs
|
101 participants
|
109 participants
|
92 participants
|
|
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Grade 2-4 Related AEs
|
2 participants
|
12 participants
|
1 participants
|
|
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Grade 3-4 Related AEs
|
5 participants
|
7 participants
|
9 participants
|
SECONDARY outcome
Timeframe: From start of study through Week 100 + 5 daysPopulation: All treated participants.
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.
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Number of Participants With Laboratory Abnormalities: Hematology
Platelets
|
13 participants
|
14 participants
|
12 participants
|
|
Number of Participants With Laboratory Abnormalities: Hematology
Hemoglobin
|
8 participants
|
9 participants
|
11 participants
|
|
Number of Participants With Laboratory Abnormalities: Hematology
White Blood Cells
|
53 participants
|
48 participants
|
38 participants
|
|
Number of Participants With Laboratory Abnormalities: Hematology
Neutrophils
|
14 participants
|
17 participants
|
15 participants
|
|
Number of Participants With Laboratory Abnormalities: Hematology
International Normalized Ratio
|
8 participants
|
7 participants
|
9 participants
|
SECONDARY outcome
Timeframe: On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeksPopulation: All treated participants. n = number of participants in the OF period.
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
Outcome measures
| Measure |
ETV+ADV Combination Therapy
n=138 Participants
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
ETV Monotherapy
n=140 Participants
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+LVD Combination Therapy
n=137 Participants
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
|---|---|---|---|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Alanine aminotransferase (ALT)
|
76 participants
|
83 participants
|
74 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Aspartate aminotransferase (AST)
|
60 participants
|
62 participants
|
53 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Alkaline Phosphatase (ALP)
|
8 participants
|
4 participants
|
6 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Albumin
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Serum Lipase
|
24 participants
|
33 participants
|
24 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Creatinine
|
2 participants
|
2 participants
|
4 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Blood Urea Nitrogen
|
0 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hyperglycemia
|
39 participants
|
46 participants
|
37 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hypoglycemia
|
9 participants
|
5 participants
|
9 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hypernatremia
|
10 participants
|
10 participants
|
10 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hyponatremia
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hyperkalemia
|
3 participants
|
4 participants
|
5 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hypokalemia
|
4 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hyperchloremia
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Hypochloremia
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
ALT flare - Ontreatment
|
3 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Laboratory Abnormalities: Serum Chemistry
ALT flare - Offtreatment
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
ADV + LVD Combination Therapy
ETV Monotherapy
ETV + ADV Combination Therapy
Serious adverse events
| Measure |
ADV + LVD Combination Therapy
n=137 participants at risk
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
ETV Monotherapy
n=140 participants at risk
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 + ADV Combination Therapy
n=138 participants at risk
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.73%
1/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
1.4%
2/138 • Up to Week 96
|
|
Nervous system disorders
Intracranial hypotension
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Gastrointestinal disorders
Melaena
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Infections and infestations
Pelvic infection
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Renal and urinary disorders
Ureteric stenosis
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Nervous system disorders
Dizziness
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/137 • Up to Week 96
|
2.1%
3/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Infections and infestations
Appendicitis
|
0.00%
0/137 • Up to Week 96
|
1.4%
2/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.73%
1/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
General disorders
Asthenia
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Infections and infestations
Hepatitis B
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Infections and infestations
Meningitis tuberculous
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Eye disorders
Optic atrophy
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
General disorders
Pyrexia
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Gastrointestinal disorders
Erosive oesophagitis
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
1.5%
2/137 • Up to Week 96
|
3.6%
5/140 • Up to Week 96
|
2.9%
4/138 • Up to Week 96
|
|
Nervous system disorders
Hydrocephalus
|
0.73%
1/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Limb crushing injury
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Vascular disorders
Hot flush
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Vascular disorders
Aneurysm ruptured
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Congenital, familial and genetic disorders
Congenital cystic kidney disease
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
General disorders
Fatigue
|
0.73%
1/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast
|
0.00%
0/137 • Up to Week 96
|
0.71%
1/140 • Up to Week 96
|
0.00%
0/138 • Up to Week 96
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/137 • Up to Week 96
|
0.00%
0/140 • Up to Week 96
|
0.72%
1/138 • Up to Week 96
|
Other adverse events
| Measure |
ADV + LVD Combination Therapy
n=137 participants at risk
ADV 10 mg + LVD 100 mg; QD for 100 weeks
|
ETV Monotherapy
n=140 participants at risk
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 + ADV Combination Therapy
n=138 participants at risk
ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
|
|---|---|---|---|
|
Hepatobiliary disorders
Hepatic steatosis
|
6.6%
9/137 • Up to Week 96
|
5.7%
8/140 • Up to Week 96
|
2.9%
4/138 • Up to Week 96
|
|
Investigations
Aspartate aminotransferase increased
|
0.73%
1/137 • Up to Week 96
|
5.0%
7/140 • Up to Week 96
|
3.6%
5/138 • Up to Week 96
|
|
Nervous system disorders
Headache
|
9.5%
13/137 • Up to Week 96
|
3.6%
5/140 • Up to Week 96
|
5.8%
8/138 • Up to Week 96
|
|
Infections and infestations
Upper respiratory tract infection
|
13.9%
19/137 • Up to Week 96
|
20.0%
28/140 • Up to Week 96
|
16.7%
23/138 • Up to Week 96
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.4%
6/137 • Up to Week 96
|
7.1%
10/140 • Up to Week 96
|
3.6%
5/138 • Up to Week 96
|
|
Vascular disorders
Hypertension
|
2.2%
3/137 • Up to Week 96
|
5.0%
7/140 • Up to Week 96
|
1.4%
2/138 • Up to Week 96
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.1%
7/137 • Up to Week 96
|
2.1%
3/140 • Up to Week 96
|
5.8%
8/138 • Up to Week 96
|
|
Investigations
Alanine aminotransferase increased
|
3.6%
5/137 • Up to Week 96
|
5.7%
8/140 • Up to Week 96
|
5.8%
8/138 • Up to Week 96
|
|
Gastrointestinal disorders
Nausea
|
2.9%
4/137 • Up to Week 96
|
5.7%
8/140 • Up to Week 96
|
4.3%
6/138 • Up to Week 96
|
|
Gastrointestinal disorders
Dyspepsia
|
5.8%
8/137 • Up to Week 96
|
4.3%
6/140 • Up to Week 96
|
7.2%
10/138 • Up to Week 96
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
7/137 • Up to Week 96
|
3.6%
5/140 • Up to Week 96
|
1.4%
2/138 • Up to Week 96
|
|
General disorders
Fatigue
|
5.8%
8/137 • Up to Week 96
|
2.9%
4/140 • Up to Week 96
|
2.9%
4/138 • Up to Week 96
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
8/137 • Up to Week 96
|
12.1%
17/140 • Up to Week 96
|
12.3%
17/138 • Up to Week 96
|
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