Trial Outcomes & Findings for Lamivudine and Adefovir to Treat Chronic Hepatitis B (NCT NCT00023309)
NCT ID: NCT00023309
Last Updated: 2016-09-23
Results Overview
A maintained combined response was defined as a combination of a virological, biochemical and histological responses at weeks 48 and 192. A virological response was defined as a decrease in HBV DNA levels to undetectable by the Amplicor assay (\<500 copies/mL). A biochemical response was defined as a decrease in serum ALT levels into the normal range (\<41 U/L). A histological response was defined as a decrease in the HAI score by at least three points with no worsening of the Ishak fibrosis score.
COMPLETED
PHASE2
41 participants
196 weeks from randomization
2016-09-23
Participant Flow
Forty-one patients were enrolled, twenty-two were randomized to receive the combination lamivudine and adefovir and nineteen to receive adefovir alone.
Participant milestones
| Measure |
Lamivudine and Adefovir
Patients to receive combination lamivudine and adefovir, with lamivudine of 100 mg daily and adefovir of 10 mg daily
|
Adefovir
Patients to receive adefovir alone (10 mg daily).
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
19
|
|
Overall Study
COMPLETED
|
22
|
19
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lamivudine and Adefovir to Treat Chronic Hepatitis B
Baseline characteristics by cohort
| Measure |
Lamivudine and Adefovir
n=22 Participants
Patients to receive combination lamivudine and adefovir
|
Adefovir
n=19 Participants
Patients to receive adefovir alone
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46 years
STANDARD_DEVIATION 14 • n=99 Participants
|
45 years
STANDARD_DEVIATION 13 • n=107 Participants
|
45 years
STANDARD_DEVIATION 14 • n=206 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
9 participants
n=99 Participants
|
8 participants
n=107 Participants
|
17 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
9 participants
n=99 Participants
|
10 participants
n=107 Participants
|
19 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 participants
n=99 Participants
|
1 participants
n=107 Participants
|
5 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=99 Participants
|
19 participants
n=107 Participants
|
41 participants
n=206 Participants
|
|
Treatment Naive
Yes
|
17 participants
n=99 Participants
|
14 participants
n=107 Participants
|
31 participants
n=206 Participants
|
|
Treatment Naive
No
|
5 participants
n=99 Participants
|
5 participants
n=107 Participants
|
10 participants
n=206 Participants
|
|
HBeAg positive
Yes
|
17 participants
n=99 Participants
|
14 participants
n=107 Participants
|
31 participants
n=206 Participants
|
|
HBeAg positive
No
|
5 participants
n=99 Participants
|
5 participants
n=107 Participants
|
10 participants
n=206 Participants
|
|
ALT
|
183 IU/ml
STANDARD_DEVIATION 250 • n=99 Participants
|
87 IU/ml
STANDARD_DEVIATION 56 • n=107 Participants
|
139 IU/ml
STANDARD_DEVIATION 187 • n=206 Participants
|
|
HBV DNA Log 10 copies per ml
|
8.1 log10(copies/ml)
STANDARD_DEVIATION 1.3 • n=99 Participants
|
7.8 log10(copies/ml)
STANDARD_DEVIATION 1.6 • n=107 Participants
|
8.0 log10(copies/ml)
STANDARD_DEVIATION 1.4 • n=206 Participants
|
|
HAI
|
8.1 Units on a scale
STANDARD_DEVIATION 2.7 • n=99 Participants
|
7.9 Units on a scale
STANDARD_DEVIATION 2.4 • n=107 Participants
|
8.0 Units on a scale
STANDARD_DEVIATION 2.6 • n=206 Participants
|
|
Ishak
|
3.3 Units on a scale
STANDARD_DEVIATION 1.7 • n=99 Participants
|
2.4 Units on a scale
STANDARD_DEVIATION 1.5 • n=107 Participants
|
2.9 Units on a scale
STANDARD_DEVIATION 1.6 • n=206 Participants
|
|
Cirrhosis
Yes
|
5 participants
n=99 Participants
|
2 participants
n=107 Participants
|
7 participants
n=206 Participants
|
|
Cirrhosis
No
|
17 participants
n=99 Participants
|
17 participants
n=107 Participants
|
34 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 196 weeks from randomizationPopulation: The analysis was intention to treat. Patients with missing values at week 196 were treated as random missing. No imputation was applied.
A maintained combined response was defined as a combination of a virological, biochemical and histological responses at weeks 48 and 192. A virological response was defined as a decrease in HBV DNA levels to undetectable by the Amplicor assay (\<500 copies/mL). A biochemical response was defined as a decrease in serum ALT levels into the normal range (\<41 U/L). A histological response was defined as a decrease in the HAI score by at least three points with no worsening of the Ishak fibrosis score.
Outcome measures
| Measure |
Lamivudine and Adefovir
n=22 Participants
Patients to receive combination lamivudine and adefovir
|
Adefovir
n=19 Participants
Patients to receive adefovir alone
|
|---|---|---|
|
Maintained Combined Response (Virological, Biochemical and Histological Response).
Yes
|
15 participants
|
6 participants
|
|
Maintained Combined Response (Virological, Biochemical and Histological Response).
No
|
7 participants
|
13 participants
|
SECONDARY outcome
Timeframe: Week 196 from randomizationPopulation: Analysis was intention to treat. Patients with missing values at timeframe of interest was taken as random missing. No imputation was applied.
Loss of hepatitis B surface antigen (HBsAg) at week 196
Outcome measures
| Measure |
Lamivudine and Adefovir
n=17 Participants
Patients to receive combination lamivudine and adefovir
|
Adefovir
n=14 Participants
Patients to receive adefovir alone
|
|---|---|---|
|
HBeAg Loss at Week 196
No
|
4 participants
|
9 participants
|
|
HBeAg Loss at Week 196
Yes
|
13 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Week 196 from randomizationPopulation: Intention to treat
A virological response was defined as a decrease in HBV DNA levels to undetectable by the Amplicor assay (\<500 copies/mL).
Outcome measures
| Measure |
Lamivudine and Adefovir
n=22 Participants
Patients to receive combination lamivudine and adefovir
|
Adefovir
n=19 Participants
Patients to receive adefovir alone
|
|---|---|---|
|
Virological Response
Yes
|
17 participants
|
6 participants
|
|
Virological Response
No
|
5 participants
|
13 participants
|
SECONDARY outcome
Timeframe: week 196 from randomizationPopulation: Intention to treat
A biochemical response was defined as a decrease in serum ALT levels into the normal range (\<41 U/L).
Outcome measures
| Measure |
Lamivudine and Adefovir
n=22 Participants
Patients to receive combination lamivudine and adefovir
|
Adefovir
n=19 Participants
Patients to receive adefovir alone
|
|---|---|---|
|
Biological Response
Yes
|
21 participants
|
12 participants
|
|
Biological Response
No
|
1 participants
|
7 participants
|
SECONDARY outcome
Timeframe: week 196 from randomizationPopulation: Analysis was intention to treat. Patients with missing values at timeframe of interest was taken as random missing. No imputation was applied.
A histological response was defined as a decrease in the HAI score by at least three points with no worsening of the Ishak fibrosis score.
Outcome measures
| Measure |
Lamivudine and Adefovir
n=18 Participants
Patients to receive combination lamivudine and adefovir
|
Adefovir
n=10 Participants
Patients to receive adefovir alone
|
|---|---|---|
|
Histological Response
Yes
|
15 participants
|
5 participants
|
|
Histological Response
No
|
3 participants
|
5 participants
|
Adverse Events
Lamivudine and Adefovir
Adefovir
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Marc G. Ghany, M.D
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place