Trial Outcomes & Findings for A Study of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus (HBV)-Infection (NCT NCT00423891)
NCT ID: NCT00423891
Last Updated: 2018-05-02
Results Overview
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Medical Dictionary for Regulatory Activities (MedDRA) version 16.0 was used.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
64 participants
Primary outcome timeframe
Day 1 to Week 120
Results posted on
2018-05-02
Participant Flow
64 enrolled. 48 treated. Participants received a minimum of 48 weeks study drug but depending on response to drug, could remain on treatment for up to a total of 120 weeks. Participants were to receive post dosing follow up after last dose, for a total of 5 years on-study (on and off study drug).
Participant milestones
| Measure |
Lamivudine (LVD)-Naive (Group A)
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Enrolled
STARTED
|
35
|
21
|
8
|
|
Enrolled
COMPLETED
|
24
|
19
|
5
|
|
Enrolled
NOT COMPLETED
|
11
|
2
|
3
|
|
Treatment
STARTED
|
24
|
19
|
5
|
|
Treatment
COMPLETED
|
22
|
19
|
5
|
|
Treatment
NOT COMPLETED
|
2
|
0
|
0
|
|
Post-Dosing Follow Up
STARTED
|
22
|
18
|
5
|
|
Post-Dosing Follow Up
COMPLETED
|
20
|
15
|
3
|
|
Post-Dosing Follow Up
NOT COMPLETED
|
2
|
3
|
2
|
Reasons for withdrawal
| Measure |
Lamivudine (LVD)-Naive (Group A)
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Enrolled
Withdrawal by Subject
|
0
|
0
|
1
|
|
Enrolled
Lost to Follow-up
|
0
|
0
|
1
|
|
Enrolled
No longer met criteria
|
11
|
2
|
1
|
|
Treatment
Withdrawal by Subject
|
1
|
0
|
0
|
|
Treatment
Lost to Follow-up
|
1
|
0
|
0
|
|
Post-Dosing Follow Up
Withdrawal by Subject
|
0
|
3
|
2
|
|
Post-Dosing Follow Up
Lost to Follow-up
|
2
|
0
|
0
|
Baseline Characteristics
A Study of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus (HBV)-Infection
Baseline characteristics by cohort
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
9.2 years
STANDARD_DEVIATION 5.41 • n=5 Participants
|
11.0 years
STANDARD_DEVIATION 4.42 • n=7 Participants
|
8.8 years
STANDARD_DEVIATION 5.02 • n=5 Participants
|
9.9 years
STANDARD_DEVIATION 4.98 • n=4 Participants
|
|
Age, Customized
≥ 2 years to ≤ 6 years
|
7 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Age, Customized
>6 years to ≤ 12 years
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
2 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Age, Customized
>12 years to ≤18 years
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
1 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
17 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
5 participants
n=7 Participants
|
1 participants
n=5 Participants
|
16 participants
n=4 Participants
|
|
Region of Enrollment
Taiwan
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
3 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
Argentina
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Region of Enrollment
Belgium
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Brazil
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Region of Enrollment
Korea, Republic of
|
3 participants
n=5 Participants
|
9 participants
n=7 Participants
|
4 participants
n=5 Participants
|
16 participants
n=4 Participants
|
|
Hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
|
7.92 log10 IU/mL
STANDARD_DEVIATION 0.864 • n=5 Participants
|
7.74 log10 IU/mL
STANDARD_DEVIATION 0.856 • n=7 Participants
|
7.96 log10 IU/mL
STANDARD_DEVIATION 0.238 • n=5 Participants
|
7.85 log10 IU/mL
STANDARD_DEVIATION 0.812 • n=4 Participants
|
|
Alanine Aminotransferase (ALT)
|
142.8 U/L
STANDARD_DEVIATION 85.18 • n=5 Participants
|
125.7 U/L
STANDARD_DEVIATION 67.96 • n=7 Participants
|
44.6 U/L
STANDARD_DEVIATION 22.96 • n=5 Participants
|
125.8 U/L
STANDARD_DEVIATION 78.83 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 120Population: All participants who received at least one dose of study drug. On-treatment period began on the first day of study therapy and ended 5 days after the last dose of study therapy.
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Medical Dictionary for Regulatory Activities (MedDRA) version 16.0 was used.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment
Serious Adverse Events (n=24, 19, 5)
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment
Discontinuations Due to AEs (n=24,19,5)
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 14Population: Participants in Groups A and B who received study drug and had PK assessment.
Cmax and Cmin were derived from plasma concentration of ETV versus time and measured in nanograms per milliliters (ng/mL). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. Note: PK parameters were summarized for only Groups A and B. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
Cmax of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
|
8.07 ng/mL
Geometric Coefficient of Variation 24
|
16.03 ng/mL
Geometric Coefficient of Variation 8
|
—
|
|
Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
Cmax of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
|
6.29 ng/mL
Geometric Coefficient of Variation 25
|
19.01 ng/mL
Geometric Coefficient of Variation 15
|
—
|
|
Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
Cmax of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
|
5.11 ng/mL
Geometric Coefficient of Variation 27
|
11.32 ng/mL
Geometric Coefficient of Variation 37
|
—
|
|
Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
Cmin of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
|
0.244 ng/mL
Geometric Coefficient of Variation 32
|
0.468 ng/mL
Geometric Coefficient of Variation 17
|
—
|
|
Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
Cmin of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
|
0.320 ng/mL
Geometric Coefficient of Variation 22
|
0.497 ng/mL
Geometric Coefficient of Variation 32
|
—
|
|
Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
Cmin of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
|
0.271 ng/mL
Geometric Coefficient of Variation 25
|
0.455 ng/mL
Geometric Coefficient of Variation 25
|
—
|
SECONDARY outcome
Timeframe: Day 14Population: Participants in Groups A and B who received study drug and had PK assessment.
Tmax was derived from plasma concentration of ETV versus time and measured in hours (h). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. Age categories presented below: participants age as of first day of dosing. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort
Tmax of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
|
0.50 h
Interval 0.5 to 1.0
|
1.00 h
Interval 0.5 to 1.5
|
—
|
|
Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort
Tmax of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
|
0.57 h
Interval 0.5 to 2.0
|
0.72 h
Interval 0.5 to 1.0
|
—
|
|
Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort
Tmax of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
|
0.78 h
Interval 0.5 to 1.0
|
0.52 h
Interval 0.5 to 1.0
|
—
|
SECONDARY outcome
Timeframe: Day 14Population: Participants in Groups A and B who received study drug and had PK assessment.
Area under the Curve (AUC) was derived from plasma concentration of ETV versus time. AUC(TAU) was calculated by log- and linear trapezoidal summations, TAU = 24 hours, and was measured in nanograms\*hours per milliliter (ng\*h/mL). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
AUC(TAU) of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
|
15.96 ng*h/mL
Geometric Coefficient of Variation 22
|
35.36 ng*h/mL
Geometric Coefficient of Variation 24
|
—
|
|
Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
AUC(TAU) of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
|
18.69 ng*h/mL
Geometric Coefficient of Variation 21
|
42.26 ng*h/mL
Geometric Coefficient of Variation 27
|
—
|
|
Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
AUC(TAU) of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
|
20.42 ng*h/mL
Geometric Coefficient of Variation 20
|
41.50 ng*h/mL
Geometric Coefficient of Variation 21
|
—
|
SECONDARY outcome
Timeframe: At 2 weeksPopulation: Participants in Groups A and B who received study drug and had PK assessment.
CLT/F was calculated by dividing the dose of ETV by AUC(TAU) of ETV and was measured in liters per hour (L/h). Blood samples were obtained before study drug administration and at 0.5, 1, 2, 4, 8, and 24 hours after study drug administration on Day 14 (+/- 4 days) for the PK assessment. Plasma samples were analyzed for ETV with a validated method using liquid chromatography-tandem mass spectrometry detection. PK assessment was optional for Group C participants (NA-experienced participants who were included with the September 2011 country-specific protocol amendment). No Group C participants chose to participate in the PK assessment.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
CLT/F of ETV (> 6 yrs to ≤ 12 yrs), (n=9, 7)
|
22.66 L/h
Standard Deviation 6.134
|
21.67 L/h
Standard Deviation 6.940
|
—
|
|
Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
CLT/F of ETV (> 12 yrs to ≤ 18 yrs), (n=8,9)
|
31.92 L/h
Standard Deviation 6.429
|
28.95 L/h
Standard Deviation 6.496
|
—
|
|
Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
CLT/F of ETV (≥ 2 yrs to ≤ 6 yrs), (n=7, 3)
|
11.40 L/h
Standard Deviation 2.564
|
12.31 L/h
Standard Deviation 3.102
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS TaqMan - high pure system (HPS) assay and was reported in international units per milliliter (IU/mL). Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 12
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 24
|
10 participants
|
3 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 36
|
11 participants
|
6 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 48
|
14 participants
|
9 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 96
|
8 participants
|
11 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
HBeAg loss: HBeAg negative. The method used for the detection of HBe Ag was the DiaSorin - Anti HBe enzyme immunoassay kit. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
Week 12
|
3 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
Week 24
|
4 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
Week 36
|
5 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
Week 48
|
10 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
Week 96
|
5 participants
|
2 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
HBsAg loss: HBsAg negative. The method used for detection of HBsAg was the ADVIA Centaur iImmunoassay system. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
Week 24
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
Week 36
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
Week 96
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
Week 12
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
Week 48
|
1 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline through Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
HBe seroconversion: loss of HBeAg (HBeAg negative) with positive HB e antibodies (HBeAb), ie both the presence of HBeAb and the absence of HBeAg. The method used for the detection HBeAg seroconversion was the DiaSorin - Anti HBe enzyme immunoassay kit. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
Week 24
|
4 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
Week 36
|
5 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
Week 96
|
5 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
Week 12
|
3 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
Week 48
|
10 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLD = 6 IU/mL). Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
Week 12
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
Week 24
|
6 participants
|
1 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
Week 36
|
7 participants
|
5 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
Week 48
|
13 participants
|
6 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
Week 96
|
8 participants
|
8 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline through Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLQ = 29 IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
Week 12
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
Week 24
|
9 participants
|
2 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
Week 36
|
10 participants
|
5 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
Week 48
|
14 participants
|
7 participants
|
0 participants
|
|
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
Week 96
|
8 participants
|
8 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Baseline through Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
HB s Ag seroconversion: loss of HBsAg (HBsAg negative) and presence of HB s antibodies (HBsAb). The method used for the detection of HBsAg seroconversion was the ADVIA Centaur iImmunoassay system. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
Week 24
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
Week 36
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
Week 48
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
Week 96
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
Week 12
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
PDR was defined as confirmed HBV DNA \< 50 IU/mL plus confirmed HBeAg seroconversion on 2 sequential measurements at least 14 days apart. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
Week 12
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
Week 24
|
4 participants
|
0 participants
|
0 participants
|
|
Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
Week 36
|
4 participants
|
1 participants
|
0 participants
|
|
Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
Week 96
|
3 participants
|
1 participants
|
0 participants
|
|
Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
Week 48
|
7 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: Participants who received at least one dose of study drug, and had a measurement at baseline and at the specific analysis week.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. HBV DNA log10 changes from baseline were summarized over time.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
Week 12
|
-4.45 IU/mL
Standard Error 0.2418
|
-3.89 IU/mL
Standard Error 0.1592
|
-3.80 IU/mL
Standard Error 0.4657
|
|
Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
Week 24
|
-5.30 IU/mL
Standard Error 0.2744
|
-4.85 IU/mL
Standard Error 0.2900
|
-3.89 IU/mL
Standard Error 0.5440
|
|
Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
Week 36
|
-5.61 IU/mL
Standard Error 0.2580
|
-5.14 IU/mL
Standard Error 0.2604
|
-3.90 IU/mL
Standard Error 0.2499
|
|
Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
Week 48
|
-5.86 IU/mL
Standard Error 0.2176
|
-5.36 IU/mL
Standard Error 0.3032
|
-4.32 IU/mL
Standard Error 0.4794
|
|
Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
Week 96
|
-6.30 IU/mL
Standard Error 0.2576
|
-5.86 IU/mL
Standard Error 0.2222
|
-5.79 IU/mL
Standard Error 0.5308
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Normalization in ALT= ALT ≤ 1.0\*upper limit of normal (ULN). Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Baseline
|
0 participants
|
1 participants
|
2 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 24
|
15 participants
|
12 participants
|
5 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 30
|
16 participants
|
13 participants
|
5 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 36
|
16 participants
|
16 participants
|
5 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 42
|
16 participants
|
15 participants
|
5 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 48
|
20 participants
|
18 participants
|
4 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 96
|
10 participants
|
13 participants
|
3 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 4
|
1 participants
|
1 participants
|
2 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 8
|
3 participants
|
2 participants
|
2 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 12
|
5 participants
|
7 participants
|
3 participants
|
|
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
Week 18
|
15 participants
|
10 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48, Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. LLQ = 29 IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Baseline >=17,200 IU/mL
|
24 participants
|
19 participants
|
5 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 48: 50 - < 172 IU/mL
|
1 participants
|
2 participants
|
0 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 48: 172 - < 1720 IU/mL
|
3 participants
|
3 participants
|
1 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 48: 1720 - < 17,200 IU/mL
|
3 participants
|
1 participants
|
3 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 48: > = 17,200 IU/mL
|
1 participants
|
3 participants
|
1 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 96: < 50 IU/mL
|
8 participants
|
11 participants
|
2 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 96: 50 - < 172 IU/mL
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 48: < 50 IU/mL
|
14 participants
|
9 participants
|
0 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 96: 172 - < 1720 IU/mL
|
3 participants
|
0 participants
|
1 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 96: 1720 - < 17,200 IU/mL
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
Week 96: > = 17,200 IU/mL
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0\*ULN.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 12
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 48
|
13 participants
|
9 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 96
|
7 participants
|
11 participants
|
2 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 24
|
10 participants
|
3 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
Week 36
|
11 participants
|
4 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0\*ULN. HBe seroconversion was determination of presence of HBeAb and loss of HBeAg. The method used for the detection of HBeAg seroconversion was the DiaSorin - Anti HBe enzyme immunoassay kit.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
Week 36
|
4 participants
|
1 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
Week 48
|
8 participants
|
3 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
Week 96
|
3 participants
|
1 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
Week 12
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
Week 24
|
4 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to Week 96Population: The intent-to-treat method of Non-Completer = Failure was used through Week 48 in which all treated participants were analyzed, and participants with missing data at the analysis week were considered failures. After Week 48, the method of Non-Completer = Missing was used, in which participants with missing data at the analysis week were excluded.
Hepatitis B virus DNA by PCR was measured using the Roche COBAS TaqMan - HPS assay and was reported in IU/mL. Baseline was the last value measured prior to or on the date of the first dose of study therapy. Normalization in ALT= ALT ≤ 1.0\*ULN. HBe seroconversion: loss of HBeAg (HBeAg negative) with positive HBeAb. The method used for the detection of HBeAg/Ab serologies was the DiaSorin enzyme immunoassay kit.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
Baseline
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
Week 12
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
Week 24
|
6 participants
|
3 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
Week 36
|
7 participants
|
3 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
Week 48
|
5 participants
|
6 participants
|
0 participants
|
|
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
Week 96
|
4 participants
|
10 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Day 1 to Week 120Population: Participants who received at least 1 dose of study therapy, and had a measurement during the on-treatment period (i.e., after the first day of study therapy through 5 days after the last dose of study therapy).
Toxicity Scale: Division of AIDs (DAIDS) grades Version 1.0. Upper limit of normal (ULN); lower limit of normal (LLN); Cells per Liter (c/L); cells per microliter (c/µL); grams per deciliter (g/dL); milliequivalents per liter (mEq/L); cells per microliter (c/µL): Grade (Gr). Hemoglobin g/dL: Gr1:10.0-10.9;Gr2: 9.0-9.9; Gr3:7.0-8.9; Gr4: \<7.0. International normalization ratio (INR): Gr1:1.1-\<1.5\*ULN; Gr2: 1.6-\<2.0\*ULN; Gr3: 2.1-3.0\*ULN;Gr4: \>3.0\*ULN. Neutrophils/bands c/µL: Gr1;1.0-1.3\*10\^3; Gr2: 0.75-0.99\*10\^3; Gr 3: 0.50-0.749\*10\^3; Gr4: \<0.5\*10\^3.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
International normalization ratio
|
4 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Hemoglobin
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Neutrophils (absolute) + bands
|
3 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1 to Week 120Population: Participants who received at least one dose of study drug, and had a measurement during the on-treatment period (i.e., after the first day of study therapy through 5 days after the last dose of study therapy).
Toxicity Scale: DAIDS Version 1.0 and modified World Health Organization (WHO). Grade (Gr). ALT: Gr1:1.25-\<2.5\*ULN; Gr2: 2.6-\<5.0 \*ULN; Gr3: 5.1-10.0\*ULN; Gr4:\>10.0\*ULN. Aspartate aminotransferase (AST): Gr1: 1.25-\<2.5\*ULN; Gr2:2.6-\<5.0\*ULN; Gr 3: 5.1-10.0\*ULN; Gr4\>10.0\*ULN. Alkaline phosphatase: Gr1:1.25-\<2.5\*ULN; Gr2: 2.6-\<5.0\*ULN; Gr3: 5.1-10.0\*ULN; Gr4: \>10.0\*ULN. Lipase: Gr1:1.1-\<1.5\*ULN;Gr2:1.6-\<3.0\*ULN; Gr3: 3.1-5.0\*ULN; Gr4: \>5.0\*ULN. Creatinine: Gr1: 1.1-1.3\*ULN; Gr2: 1.4-\<1.8\*ULN; Gr3: 1.9 - \<3.4\*ULN; Gr4: \>=3.5\*ULN. Glucose mg/dL (high): Gr1:110-\<125 (Fasting)/116-\<160;Gr2:126-\<250 (F)/161-\<250; Gr3: 251-500; Gr4: \>500.Glucose (low): Gr1: 55-64; Gr2: 40 - \<54; Gr3: 30-39; Gr4: \<30 mg/dL.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
ALT
|
23 participants
|
17 participants
|
4 participants
|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
AST
|
14 participants
|
9 participants
|
1 participants
|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Alkaline Phosphatase
|
3 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Lipase
|
5 participants
|
12 participants
|
3 participants
|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Creatinine
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Glucose, high
|
3 participants
|
4 participants
|
1 participants
|
|
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Glucose, low
|
3 participants
|
4 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 1 Week 120Population: Participants who received at least one dose of study drug, and had a measurement during the on-treatment period (i.e., after the first day of study therapy through 5 days after the last dose of study therapy).
Toxicity Scale: DAIDS Version 1.0 and modified World Health Organization (WHO) for chloride. Milliequivalents per liter (mEq/L); Grade (Gr). Chloride high (mEq/L): Gr1: 113-\<117; Gr2: 117-\<121; Gr3: 121-125; Gr4: \>125. Potassium low (mEq/L): Gr1: 3.0-3.4; Gr2: 2.5-2.9; Gr3:2.0-\<2.4; Gr4: \<2.0. Potassium high: Gr1; 5.6- \<6.0; Gr2: 6.1-\<6.5; Gr3: 6.6-7.0; Gr4: \>7.0. Sodium high (mEq/L): Gr1; 146-\<150; Gr2: 151-\<154; Gr3: 155-\<159; Gr4: \>=160.
Outcome measures
| Measure |
Lamivudine (LVD)-Naive (Group A)
n=24 Participants
Participants with less than (\<) 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to Pharmacokinetic (PK) assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Lamivudine (LVD)-Experienced (Group B)
n=19 Participants
Participants with greater than (\>) 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Nucleoside/Tide Analog (NA) - Experienced (Group C)
n=5 Participants
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Potassium, high
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Chloride, high
|
3 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Potassium, low
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
Sodium, high
|
4 participants
|
3 participants
|
0 participants
|
Adverse Events
Group A LVD-naive
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
Group B LVD-exp
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Group C NA-exp
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group A LVD-naive
n=24 participants at risk
Participants with \< 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Group B LVD-exp
n=19 participants at risk
Participants with \> 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Group C NA-exp
n=5 participants at risk
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Infections and infestations
Gastroenteritis
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Pneumonia
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Investigations
Alanine aminotransferase increased
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
Other adverse events
| Measure |
Group A LVD-naive
n=24 participants at risk
Participants with \< 1 week of prior LVD therapy and with no LVD therapy within 24 weeks prior to enrollment were included in Group A. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\>6 years to ≤ 12 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, once a day (QD) and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.015 mg/kg up to 0.5 mg, or ETV tablets, 0.5 mg, QD. Following PK analysis, those who met the specified dosing requirements (at least 0.5 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Group B LVD-exp
n=19 participants at risk
Participants with \> 12 weeks of prior LVD therapy were included in Group B. Prior to PK assessment, Cohort 1 (age ≥ 2 years to ≤ 6 years) and Cohort 2 (\> 6 years to ≤ 12 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, QD and Cohort 3 (age \>12 years to ≤18 years) received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg QD. Following PK analysis, those who met the specified dosing requirements (at least 1.0 mg/day) and could tolerate swallowing ETV tablets were allowed to choose either formulation. Entecavir (ETV) was administered for a maximum of 120 weeks.
|
Group C NA-exp
n=5 participants at risk
Participants who failed previous treatment with any non-ETV nucleoside/tide analog (NA) were included in Group C, starting in 2011. PK assessment was optional to participants in Group C. All participants received ETV oral solution, 0.030 mg/kg up to 1.0 mg, or ETV tablets, 1.0 mg, QD. Participants who met the specified dosing requirements (at least 1.0 mg/day for NA-experienced participants) and could tolerate swallowing ETV tablets were allowed to choose either formulation. ETV was administered for a maximum of 120 weeks.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Eye disorders
Eye haemorrhage
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
4/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
21.1%
4/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Dental caries
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
20.8%
5/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
15.8%
3/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Enteritis
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Faeces soft
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Mouth ulceration
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Nausea
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Tooth impacted
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
21.1%
4/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
General disorders
Chest pain
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
General disorders
Fatigue
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
General disorders
Influenza like illness
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
General disorders
Pyrexia
|
41.7%
10/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
26.3%
5/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Ear infection
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Impetigo
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Influenza
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Lyme disease
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Molluscum contagiosum
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Mumps
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Otitis externa
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Otitis media acute
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Pharyngotonsillitis
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Sinusitis
|
12.5%
3/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
41.7%
10/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
15.8%
3/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
40.0%
2/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Infections and infestations
Viral upper respiratory tract infection
|
16.7%
4/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
47.4%
9/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Injury, poisoning and procedural complications
Limb injury
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Nervous system disorders
Dizziness
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Nervous system disorders
Headache
|
29.2%
7/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
26.3%
5/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Product Issues
Product taste abnormal
|
4.2%
1/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Psychiatric disorders
Mood swings
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
29.2%
7/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
26.3%
5/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
3/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
12.5%
3/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
2/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
10.5%
2/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
20.0%
1/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/24 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
5.3%
1/19 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
0.00%
0/5 • From first dose to date of last dose plus 5 days, up to 120 weeks
|
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