Trial Outcomes & Findings for Suboptimal Responders to Adefovir Switching to Entecavir (NCT NCT00718887)
NCT ID: NCT00718887
Last Updated: 2013-02-11
Results Overview
HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
228 participants
Primary outcome timeframe
At Week 12 from Day 1
Results posted on
2013-02-11
Participant Flow
A total of 228 participants were enrolled, of which 169 were randomized. A total of 166 participants received treatment.
Participant milestones
| Measure |
Entecavir, 0.5 mg QD
Participants with a pervious suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD), for a maximum of 52 weeks.
|
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD, for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
89
|
77
|
|
Overall Study
COMPLETED
|
84
|
68
|
|
Overall Study
NOT COMPLETED
|
5
|
9
|
Reasons for withdrawal
| Measure |
Entecavir, 0.5 mg QD
Participants with a pervious suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD), for a maximum of 52 weeks.
|
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD, for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Not identified
|
2
|
7
|
Baseline Characteristics
Suboptimal Responders to Adefovir Switching to Entecavir
Baseline characteristics by cohort
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a pervious suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD), for a maximum of 52 weeks.
|
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD, for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
Total
n=166 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
32.6 Years
n=39 Participants
|
34.1 Years
n=41 Participants
|
33.4 Years
n=35 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=39 Participants
|
10 Participants
n=41 Participants
|
24 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
75 Participants
n=39 Participants
|
67 Participants
n=41 Participants
|
142 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian
|
89 Participants
n=39 Participants
|
77 Participants
n=41 Participants
|
166 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: At Week 12 from Day 1Population: Participants who were randomized and received at least 1 dose of study drug.
HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing
|
5.6 Percentage of participants
|
0.0 Percentage of participants
|
SECONDARY outcome
Timeframe: At Week 48 from Day 1Population: Participants who were randomized and received at least 1 dose of study drug.
HBV=hepatitis B virus. HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing
|
31.5 Percentage of participants
|
28.6 Percentage of participants
|
SECONDARY outcome
Timeframe: At Weeks 12 and 48 from Day 1Population: Participants who were randomized and received at least 1 dose of study drug. n=number of evaluable participants.
HBV=hepatitis B virus
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing
Week 12 (n=88, 77)
|
-2.5 log10 IU/mL
Standard Deviation 1.2
|
-0.2 log10 IU/mL
Standard Deviation 1.1
|
|
Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing
Week 48 (n=87, 71)
|
-3.3 log10 IU/mL
Standard Deviation 1.5
|
-3.2 log10 IU/mL
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: At Weeks 12 and 48 from Day 1Population: Participants who were randomized, who received at least 1 dose of study drug, and whose ALT values were \>1\*ULN at baseline. n=number of evaluable participants.
ULN=upper limit of normal. ALT normalization= ≤1\*ULN, among participants with baseline ALT \>1\*ULN
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)
Week 12 (n=51, 36)
|
31.4 Percentage of participants
|
22.2 Percentage of participants
|
|
Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)
Week 48 (n=51, 36)
|
60.8 Percentage of participants
|
47.2 Percentage of participants
|
SECONDARY outcome
Timeframe: At Weeks 12 and 48 from Day 1Population: Participants who were randomized, who received at least 1 dose of study drug, and who were HBeAg-positive at baseline. n=number of evaluable participants.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion
HBeAG loss Week 48 (n=79, 72)
|
7.6 Percentage of participants
|
6.9 Percentage of participants
|
|
Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion
HBe seroconversion Week 12 (n=79, 72)
|
2.5 Percentage of participants
|
1.45 Percentage of participants
|
|
Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion
HBeAG loss Week 12 (n=79, 72)
|
3.8 Percentage of participants
|
6.9 Percentage of participants
|
|
Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion
HBe seroconversion Week 48 (n=79, 72)
|
3.8 Percentage of participants
|
2.8 Percentage of participants
|
SECONDARY outcome
Timeframe: At Weeks 12 and 48 from Day 1Population: Participants who were randomized and received at least 1 dose of study drug. n=number of evaluable participants.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
Week 12 HBsAg loss
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
Week 48 HBsAg loss
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
Week 12 HBsAg seroconversion
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion
Week 48 HBsAg seroconversion
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Week 48 from Day 1Population: Participants who were randomized and received at least 1 dose of study drug. n=number of evaluable participants.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Number of Participants With Genotypic Resistance to Entecavir
At baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Genotypic Resistance to Entecavir
Week 48
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Continually from Day 1 through Week 48, and through 24-week follow-up periodPopulation: Participants who were randomized and received at least 1 dose of study drug.
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. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study drug.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
SAEs
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
Treatment-related SAEs
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
Abnormalities in LTR leading to discontinuation
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
All AEs
|
16 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
Treatment-related AEs
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
Death
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation
AEs leading to discontinuation
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Week 48Population: Participants who were randomized and received at least 1 dose of study drug.
Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.
Outcome measures
| Measure |
Entecavir, 0.5 mg QD
n=89 Participants
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD) for a maximum of 52 weeks.
|
Adefovir, 10 mg QD
n=77 Participants
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results
Alanine aminotransferase
|
9 Percentage of participants
|
5.2 Percentage of participants
|
|
Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results
Aspartate aminotransferase
|
2.2 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results
Hyperkalemia
|
0 Percentage of participants
|
1 Percentage of participants
|
|
Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results
Hematology
|
0 Percentage of participants
|
0 Percentage of participants
|
Adverse Events
Entecavir, 0.5 mg QD
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Entecavir, 0.5 mg QD
n=89 participants at risk
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD), for a maximum of 52 weeks.
|
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
n=77 participants at risk
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD, for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Hepatobiliary disorders
Drug hepatitis
|
1.1%
1/89
|
0.00%
0/77
|
Other adverse events
| Measure |
Entecavir, 0.5 mg QD
n=89 participants at risk
Participants with a previous suboptimal response to adefovir received entecavir, 0.5 mg once daily (QD), for a maximum of 52 weeks.
|
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
n=77 participants at risk
Participants with a previous suboptimal response to adefovir received adefovir, 10 mg QD, for 12 weeks. At 12 weeks, participants were switched to entecavir, 0.5 mg QD, for a maximum of 40 weeks.
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
9.0%
8/89
|
11.7%
9/77
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
5/89
|
0.00%
0/77
|
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