Trial Outcomes & Findings for Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment (NCT NCT01063036)
NCT ID: NCT01063036
Last Updated: 2014-12-15
Results Overview
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
COMPLETED
PHASE3
144 participants
Week 48
2014-12-15
Participant Flow
Study initiated 17 May 2010; Week 48 Primary Endpoint 27 November 2012; Week 96 Study Completed18 February 2014. Participants with chronic Hepatitis B with surface antigen (HBsAg) who have been currently treated and experienced treatment failure were enrolled.
144 enrolled; 92 treated. Reasons for 52 never treated: physical/laboratory test findings 30; not in target population 21; no signed consent 7; medical history/concurrent disease 2; other exclusion criteria 1; unknown 3.
Participant milestones
| Measure |
Entecavir + Tenofovir
Entecavir (ETV) : Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Participants Treated With Study Drug
STARTED
|
92
|
|
Participants Treated With Study Drug
COMPLETED
|
86
|
|
Participants Treated With Study Drug
NOT COMPLETED
|
6
|
|
Post Dosing Follow-up Through 24 Weeks
STARTED
|
85
|
|
Post Dosing Follow-up Through 24 Weeks
COMPLETED
|
46
|
|
Post Dosing Follow-up Through 24 Weeks
NOT COMPLETED
|
39
|
Reasons for withdrawal
| Measure |
Entecavir + Tenofovir
Entecavir (ETV) : Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Participants Treated With Study Drug
Adverse Event
|
1
|
|
Participants Treated With Study Drug
Protocol Violation
|
1
|
|
Participants Treated With Study Drug
Withdrawal by Subject
|
2
|
|
Participants Treated With Study Drug
Lost to Follow-up
|
1
|
|
Participants Treated With Study Drug
Pregnancy
|
1
|
|
Post Dosing Follow-up Through 24 Weeks
Lost to Follow-up
|
1
|
|
Post Dosing Follow-up Through 24 Weeks
Withdrawal by Subject
|
6
|
|
Post Dosing Follow-up Through 24 Weeks
Alternative therapy started
|
32
|
Baseline Characteristics
Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment
Baseline characteristics by cohort
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Age, Continuous
|
42.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
20 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
23 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
1 participants
n=5 Participants
|
|
HBV DNA by PCR (log10 IU/mL)
|
3.674 log10 IU/mL
n=5 Participants
|
|
Baseline Hepatitis B e Antigen
Positive for Hepatitis B e antigen
|
56 participants
n=5 Participants
|
|
Baseline Hepatitis B e Antigen
Negative for Hepatitis B e antigen
|
34 participants
n=5 Participants
|
|
Baseline Hepatitis B e Antigen
missing Hepatitis B e antigen test
|
2 participants
n=5 Participants
|
|
Baseline Hepatitis B e Antibody
Positive for Hepatitis B e antibody
|
32 participants
n=5 Participants
|
|
Baseline Hepatitis B e Antibody
Negative for Hepatitis B e antibody
|
56 participants
n=5 Participants
|
|
Baseline Hepatitis B e Antibody
Intermediate Hepatitis B e antibody
|
2 participants
n=5 Participants
|
|
Baseline Hepatitis B e Antibody
missing Hepatitis B e antibody test
|
2 participants
n=5 Participants
|
|
Baseline Hepatitis B Surface Antigen
Positive for Hepatitis B Surface Antigen
|
92 participants
n=5 Participants
|
|
Baseline Hepatitis B Surface Antigen
Negative for Hepatitis B Surface Antigen
|
0 participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype A
|
21 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype B
|
2 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype C
|
1 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype D
|
35 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype E
|
4 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype G
|
1 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype H
|
1 Participants
n=5 Participants
|
|
Baseline HBV Subtype
HBV Subtype Indeterminate
|
3 Participants
n=5 Participants
|
|
Baseline HBV Subtype
Insufficient HBV DNA
|
23 Participants
n=5 Participants
|
|
Baseline HBV Subtype
Missing HBV DNA test
|
1 Participants
n=5 Participants
|
|
Treatment Failure Prior to Baseline
Primary Non-Response
|
9 participants
n=5 Participants
|
|
Treatment Failure Prior to Baseline
Virological Breakthrough
|
30 participants
n=5 Participants
|
|
Treatment Failure Prior to Baseline
Partial Virological Breakthrough
|
52 participants
n=5 Participants
|
|
Treatment Failure Prior to Baseline
Missing
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 48Population: All treated participants were analyzed (NC = F). An exact binomial 95% confidence interval was constructed.
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With a Virologic Response at Week 48 - Treated Population
|
76.1 percentage of participants
Interval 66.1 to 84.4
|
SECONDARY outcome
Timeframe: Week 24, Week 96Population: All treated participants were analyzed at Weeks 24 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population
Week 24 (n=92)
|
64.1 percentage of participants
Interval 53.5 to 73.9
|
|
Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population
Week 96 (n=92)
|
84.8 percentage of participants
Interval 75.8 to 91.4
|
SECONDARY outcome
Timeframe: Baseline to Weeks 12, 24, 48, 96Population: All treated participants with results at both baseline and on-treatment were analyzed. n=Number of treated participants with results at baseline and Week 12, Week 24, Week 48 and Week 96.
HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ. Baseline was Day 1, prior to study drug administration.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=89 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
Week 12 (n=89)
|
-2.230 log10 IU/mL
Standard Deviation 1.5339
|
|
Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
Week 24 (n=89)
|
-2.581 log10 IU/mL
Standard Deviation 1.8019
|
|
Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
Week 48 (n=88)
|
-2.829 log10 IU/mL
Standard Deviation 2.0537
|
|
Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
Week 96 (n=84)
|
-2.965 log10 IU/mL
Standard Deviation 2.1431
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 96Population: All treated participants were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
HBV DNA less than (\<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96. Percentage was calculated as number of participants with HBV DNA \< LLD at Weeks 24, 48, 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F).
Outcome measures
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
Week 24 (n=92)
|
12.0 percentage of participants
Interval 6.1 to 20.4
|
|
Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
Week 48 (n=92)
|
18.5 percentage of participants
Interval 11.1 to 27.9
|
|
Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
Week 96 (n=92)
|
16.3 percentage of participants
Interval 9.4 to 25.5
|
SECONDARY outcome
Timeframe: Baseline to Weeks 24, 48, and 96Population: All treated participants who were HBeAg-positive at baseline were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=56 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
Week 24 (n=56)
|
3.6 percentage of participants
Interval 0.4 to 12.3
|
|
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
Week 48 (n=56)
|
5.4 percentage of participants
Interval 1.1 to 14.9
|
|
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
Week 96 (n=56)
|
8.9 percentage of participants
Interval 3.0 to 19.6
|
SECONDARY outcome
Timeframe: Baseline, Weeks 24, 48, and 96Population: All treated participants who were HBeAg-positive at baseline were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=56 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
Week 24 (n=56)
|
3.6 percentage of participants
Interval 0.4 to 12.3
|
|
Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
Week 48 (n=56)
|
3.6 percentage of participants
Interval 0.4 to 12.3
|
|
Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
Week 96 (n=56)
|
1.8 percentage of participants
Interval 0.0 to 9.6
|
SECONDARY outcome
Timeframe: Baseline, Weeks 24, 48, 96Population: All treated participants who were HBsAg-positive at baseline and were analyzed at Weeks 24, 48, and 96 (NC = F). An exact binomial 95% Confidence Interval was constructed.
Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline. The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized). Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg). Treated participants (HBsAg-positive at baseline) were evaluated using NC=F. Baseline was Day 1, before start of study drug.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
Week 24 (n=92)
|
1.1 percentage of participants
Interval 0.0 to 5.9
|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
Week 48 (n=92)
|
0 percentage of participants
Confidence interval was not performed because the number of participants at Week 48 was 0.
|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
Week 96 (n=92)
|
2.2 percentage of participants
Interval 0.3 to 7.6
|
SECONDARY outcome
Timeframe: Baseline, Weeks 24, 48, and 96Population: All treated participants who were HBsAg-positive at baseline and were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline. Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline. Positive result for HBsAg was one of the inclusion criteria. Treated participants (HBsAg positive at baseline) were evaluated using NC=F. The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma \[potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized\]. Baseline was Day 1, before start of study drug.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
Week 24 (n=92)
|
1.1 percentage of participants
Interval 0.0 to 5.9
|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
Week 48 (n=92)
|
0 percentage of participants
CI was not performed because the number of participants with HBsAg loss at Week 48 was 0.
|
|
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
Week 96 (n=92)
|
1.1 percentage of participants
Interval 0.0 to 5.9
|
SECONDARY outcome
Timeframe: Day 1 to last dose of study drug plus 5 days; up to Week 96Population: All Treated participants were analyzed.
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=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. On-treatment = on Day 1 through last dose of study therapy + 5 days.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=92 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population
Treatment emergent SAE
|
6 participants
|
|
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population
Discontinuation of treatment due to AE
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline to Weeks 48, 96Population: All treated participants who met resistance testing criteria (primary non-response or virologic breakthrough) and were tested for resistance to both study drugs were analyzed. n = number of participants analyzed at Weeks 48 and 96.
Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough. Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S). Primary non-response was defined as \< 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=7 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population
Week 48 (n=5)
|
0 participants
|
|
Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population
Week 96 (n=7)
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1 to last dose of study drug plus 5 days; up to Week 96Population: N=treated participants with on-treatment laboratory test results.
Selected criteria presented in each category. Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (\>);greater than, equal to (\>=); less than (\<). Creatinine data presented below were confirmed, ie, at least 2 consecutive values. On-treatment = after Day 1 through last dose of study therapy + 5 days.
Outcome measures
| Measure |
Entecavir + Tenofovir
n=91 Participants
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
ALT > 2*Baseline(N=90)
|
9 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
ALT > 3*Baseline(N=90)
|
2 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Total bilirubin >2*Baseline (N=90)
|
11 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Total bilirubin >3*Baseline (N=90)
|
3 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Lipase > 3*Baseline (N=90)
|
4 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Creatinine increase from BL >= 20%(N=91)
|
4 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Creatinine >1.5 mg/dL (N=91)
|
2 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Creatinine clearance < 50 mL/min (N=91)
|
1 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Phosphate < 2.0 mg/dL (N=90)
|
2 participants
|
|
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Phosphate < 2.3 mg/dL (N=90)
|
8 participants
|
Adverse Events
Entecavir + Tenofovir
Serious adverse events
| Measure |
Entecavir + Tenofovir
n=92 participants at risk
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Gastrointestinal disorders
Inguinal hernia
|
1.1%
1/92 • Day 1 up to 96 Weeks
|
|
Eye disorders
Cataract
|
1.1%
1/92 • Day 1 up to 96 Weeks
|
|
Infections and infestations
Appendicitis
|
1.1%
1/92 • Day 1 up to 96 Weeks
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.1%
1/92 • Day 1 up to 96 Weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
2.2%
2/92 • Day 1 up to 96 Weeks
|
|
Injury, poisoning and procedural complications
Radius fracture
|
1.1%
1/92 • Day 1 up to 96 Weeks
|
Other adverse events
| Measure |
Entecavir + Tenofovir
n=92 participants at risk
Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks
|
|---|---|
|
Infections and infestations
Bronchitis
|
6.5%
6/92 • Day 1 up to 96 Weeks
|
|
Infections and infestations
Nasopharyngitis
|
12.0%
11/92 • Day 1 up to 96 Weeks
|
|
Gastrointestinal disorders
Nausea
|
8.7%
8/92 • Day 1 up to 96 Weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.6%
7/92 • Day 1 up to 96 Weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.4%
5/92 • Day 1 up to 96 Weeks
|
|
General disorders
Asthenia
|
6.5%
6/92 • Day 1 up to 96 Weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
7.6%
7/92 • Day 1 up to 96 Weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
6/92 • Day 1 up to 96 Weeks
|
|
Nervous system disorders
Dizziness
|
5.4%
5/92 • Day 1 up to 96 Weeks
|
|
Nervous system disorders
Headache
|
6.5%
6/92 • Day 1 up to 96 Weeks
|
|
General disorders
Fatigue
|
9.8%
9/92 • Day 1 up to 96 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