Trial Outcomes & Findings for Adefovir Dipivoxil In Compensated Chronic Hepatitis B Patients (NCT NCT00316719)
NCT ID: NCT00316719
Last Updated: 2009-10-06
Results Overview
Change from baseline was the difference of the HBV DNA copy numbers (log10) in serum collected by blood draw between baseline and Week 52
COMPLETED
PHASE3
105 participants
Baseline and Week 52
2009-10-06
Participant Flow
Participant milestones
| Measure |
Adefovir (ADV)
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
52
|
53
|
|
Overall Study
COMPLETED
|
50
|
47
|
|
Overall Study
NOT COMPLETED
|
2
|
6
|
Reasons for withdrawal
| Measure |
Adefovir (ADV)
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
6
|
|
Overall Study
Consent withdrawn
|
2
|
0
|
Baseline Characteristics
Adefovir Dipivoxil In Compensated Chronic Hepatitis B Patients
Baseline characteristics by cohort
| Measure |
Adefovir (ADV)
n=50 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=52 Participants
LAM 100 mg orally once daily for 52 weeks
|
Total
n=102 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
44 years
STANDARD_DEVIATION 9.73 • n=5 Participants
|
43.9 years
STANDARD_DEVIATION 9.95 • n=7 Participants
|
44 years
STANDARD_DEVIATION 9.79 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
50 Number of participants
n=5 Participants
|
52 Number of participants
n=7 Participants
|
102 Number of participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
50 participants
n=5 Participants
|
52 participants
n=7 Participants
|
102 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 52Population: Per Protocol Set (PPS): participants in the Full Analysis Set (all subjects who entered the study, received at least one dose of investigational product, and had at least one efficacy assessment after the treatment initiation) population with no major protocol violations
Change from baseline was the difference of the HBV DNA copy numbers (log10) in serum collected by blood draw between baseline and Week 52
Outcome measures
| Measure |
Adefovir (ADV)
n=50 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=52 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Mean Change From Baseline in Hepatitis B Virus (HBV) DNA at Week 52
|
-3.69 log10 copies/mL
Standard Deviation 1.169
|
-3.40 log10 copies/mL
Standard Deviation 1.896
|
SECONDARY outcome
Timeframe: Week 52Population: PPS
The percentages of participants with an HBV DNA level in serum of less than 400 copies/mL, which is the lower limit of detection (HBV DNA loss) at Week 52
Outcome measures
| Measure |
Adefovir (ADV)
n=50 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=52 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Percentage of Participants With HBV DNA Loss (<400 Copies/mL) at Week 52
<400 copies/mL
|
46.0 Percentage of participants
|
50.0 Percentage of participants
|
|
Percentage of Participants With HBV DNA Loss (<400 Copies/mL) at Week 52
>400 copies/mL
|
54.0 Percentage of participants
|
50.0 Percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 52Time to onset of an HBV DNA level in serum of less than 400 copies/mL was summarized using the Kaplan-Meier method. Regarding the Measured Values, the median time to onset and its upper limit for the ADV group and the upper limit of the median time to onset for the LAM group are non-estimable because they are not observed until the end of the study. The lower limit of the median time to onset for the ADV and LAM groups are 36.0 and 20.0, respectively. The median time to onset for the LAM group is 28.0
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 52Population: PPS: participants who were positive for HBeAg at baseline
Participants with loss of Hepatitis B e antigen (HBeAg) in serum collected by blood draw: Cheminoluminescent Immuno Assay (CLIA) method
Outcome measures
| Measure |
Adefovir (ADV)
n=36 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=37 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 52
With loss of HBeAg
|
16.7 percentage of participants
|
16.2 percentage of participants
|
|
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 52
Positive for HBeAg
|
93.3 percentage of participants
|
93.8 percentage of participants
|
SECONDARY outcome
Timeframe: Week 52Population: PPS: participants who were positive for HBeAg and negative for HBeAb at baseline
Participants with loss of Hepatitis B e antigen (HBeAg) and positive for anti-Hepatitis B e antibody (HBeAb) in serum collected by blood draw: CLIA method
Outcome measures
| Measure |
Adefovir (ADV)
n=31 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=34 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Percentage of Participants With Hepatitis B e Antigen/Antibody (HBeAg/Ab) Seroconversion at Week 52
With HBeAg/Ab seroconversion
|
9.7 Percentage of participants
|
5.9 Percentage of participants
|
|
Percentage of Participants With Hepatitis B e Antigen/Antibody (HBeAg/Ab) Seroconversion at Week 52
Without HBeAg/Ab seroconversion
|
90.3 Percentage of participants
|
94.1 Percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 52Time to onset with loss of HBeAg in serum collected by blood draw was summarized using the Kaplan-Meier method.: CLIA method. Regarding the Measured Values, the median time to onset and its lower limit and its upper limit for all groups are non-estimable because they are not observed until the end of the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From Baseline to Week 52Time to onset of HBeAg/Ab seroconversion in serum collected by blood draw was summarized using the Kaplan-Meier method.: CLIA method. Regarding the Measured Values, the median time to onset and its lower limit and its upper limit for all groups are non-estimable because they are not observed until the end of the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 52Population: PPS: participants who were positive for HBsAg at baseline
Participants with loss of Hepatitis B s antigen (HBsAg) in serum collected by blood draw: CLIA method
Outcome measures
| Measure |
Adefovir (ADV)
n=50 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=52 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Percentage of Participants With Hepatitis B s Antigen (HBsAg) Loss at Week 52
With loss of HBsAg
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Hepatitis B s Antigen (HBsAg) Loss at Week 52
Positive for HBsAg
|
100.0 percentage of participants
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 52Population: PPS: participants who were positive for HBsAg and negative for HBsAb at baseline
Participants with loss of Hepatitis B s antigen (HBsAg) and positive for anti-Hepatitis B s antibody (HBsAb) in serum collected by blood draw: CLIA method
Outcome measures
| Measure |
Adefovir (ADV)
n=46 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=45 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Percentage of Participants With Hepatitis B s Antigen/ Antibody (HBsAg/Ab) Seroconversion at Week 52
With HBsAg/Ab seroconversion
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Hepatitis B s Antigen/ Antibody (HBsAg/Ab) Seroconversion at Week 52
Without HBsAg/Ab seroconversion
|
100.0 percentage of participants
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 52Population: PPS
Summary statistics were displayed for serum ALT.
Outcome measures
| Measure |
Adefovir (ADV)
n=50 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=47 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Mean Alanine Aminotransferase (ALT) Level at Week 52
|
32.3 Units per Liter
Standard Deviation 14.72
|
33.0 Units per Liter
Standard Deviation 28.12
|
SECONDARY outcome
Timeframe: Week 52Population: PPS: Participants with an abnormal ALT value (\>ULN) at baseline
ALT normalization was defined as an ALT value that was in the normal range (\<= 45IU/L; upper limit of normal \[ULN\]) at Week 52 of the participants whose ALT values were abnormal (\>45IU/L) at baseline
Outcome measures
| Measure |
Adefovir (ADV)
n=46 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=51 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 52
With ALT normalization
|
82.6 Percentage of participants
|
78.4 Percentage of participants
|
|
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 52
Without ALT normalization
|
17.4 Percentage of participants
|
21.6 Percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 52Population: PPS: Participants with abnormal ALT value (\>ULN) at baseline
Time to onset of ALT normalization was summarized using the Kaplan-Meier method.
Outcome measures
| Measure |
Adefovir (ADV)
n=46 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=51 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Time to Onset of ALT Normalization
|
12.0 Week 52
Interval 8.0 to 16.0
|
12.0 Week 52
Interval 12.0 to 16.0
|
SECONDARY outcome
Timeframe: Week 52Population: PPS
Participants with resistant mutation at Week 52. LAM resistant mutation (enzyme-linked mini-sequencing assay): rtM204I/V; ADV resistant mutation (direct sequencing assay): rtN236T or rtA181T/V in HBV DNA ; rt: reverse transcriptase gene
Outcome measures
| Measure |
Adefovir (ADV)
n=50 Participants
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=52 Participants
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Rate of Emergence of Resistant Virus at Week 52
With resistant mutation
|
0 Percentage of participants
|
28.8 Percentage of participants
|
|
Rate of Emergence of Resistant Virus at Week 52
Without resistant mutation
|
100 Percentage of participants
|
71.2 Percentage of participants
|
Adverse Events
Adefovir (ADV)
Lamivudine (LAM)
Serious adverse events
| Measure |
Adefovir (ADV)
n=52 participants at risk
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=53 participants at risk
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/52
|
1.9%
1/53
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/52
|
1.9%
1/53
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.00%
0/52
|
1.9%
1/53
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/52
|
1.9%
1/53
|
Other adverse events
| Measure |
Adefovir (ADV)
n=52 participants at risk
ADV 10 mg orally once daily for 52 weeks
|
Lamivudine (LAM)
n=53 participants at risk
LAM 100 mg orally once daily for 52 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
13.5%
7/52
|
11.3%
6/53
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.8%
3/52
|
3.8%
2/53
|
|
Gastrointestinal disorders
Nausea
|
1.9%
1/52
|
7.5%
4/53
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/52
|
5.7%
3/53
|
|
Infections and infestations
Nasopharyngitis
|
21.2%
11/52
|
35.8%
19/53
|
|
Infections and infestations
Upper respiratory tract inflammation
|
13.5%
7/52
|
18.9%
10/53
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
3.8%
2/52
|
9.4%
5/53
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.8%
2/52
|
5.7%
3/53
|
|
Skin and subcutaneous tissue disorders
Eczema
|
9.6%
5/52
|
5.7%
3/53
|
|
Investigations
Blood creatine phosphokinase increased
|
9.6%
5/52
|
7.5%
4/53
|
|
General disorders
Malaise
|
3.8%
2/52
|
9.4%
5/53
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.8%
3/52
|
0.00%
0/53
|
|
Nervous system disorders
Headache
|
1.9%
1/52
|
7.5%
4/53
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/52
|
11.3%
6/53
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER