Trial Outcomes & Findings for Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept (NCT NCT01379508)
NCT ID: NCT01379508
Last Updated: 2018-11-05
Results Overview
The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the "treating missing as failure" analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as "missing data."
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
241 participants
Primary outcome timeframe
week 52
Results posted on
2018-11-05
Participant Flow
Participant milestones
| Measure |
LdT Mono at Week 24
Patients who were initially treated with telbivudine and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 600 mg telbivudine daily after Week 24
|
LdT+TDF at Week 24
Patients who were initially treated with telbivudine and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 600 mg telbivudine daily and additional 300 mg tenofovir after Week 24.
|
TDF Mono at Week 24
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
|---|---|---|---|---|
|
Treatment to Week 104
STARTED
|
99
|
22
|
109
|
11
|
|
Treatment to Week 104
Completed Wk 24
|
93
|
22
|
107
|
11
|
|
Treatment to Week 104
Treatment Exposure ≥ 52 Weeks
|
91
|
21
|
105
|
11
|
|
Treatment to Week 104
COMPLETED
|
80
|
19
|
96
|
11
|
|
Treatment to Week 104
NOT COMPLETED
|
19
|
3
|
13
|
0
|
|
Extension Period Weeks 109-156
STARTED
|
64
|
17
|
79
|
10
|
|
Extension Period Weeks 109-156
COMPLETED
|
45
|
14
|
65
|
10
|
|
Extension Period Weeks 109-156
NOT COMPLETED
|
19
|
3
|
14
|
0
|
Reasons for withdrawal
| Measure |
LdT Mono at Week 24
Patients who were initially treated with telbivudine and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 600 mg telbivudine daily after Week 24
|
LdT+TDF at Week 24
Patients who were initially treated with telbivudine and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 600 mg telbivudine daily and additional 300 mg tenofovir after Week 24.
|
TDF Mono at Week 24
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
|---|---|---|---|---|
|
Treatment to Week 104
Adverse Event
|
2
|
0
|
5
|
0
|
|
Treatment to Week 104
Abnormal lab value
|
1
|
0
|
0
|
0
|
|
Treatment to Week 104
Abnormal test procedure result(s)
|
1
|
0
|
0
|
0
|
|
Treatment to Week 104
Withdrawal by Subject
|
6
|
1
|
4
|
0
|
|
Treatment to Week 104
Lost to Follow-up
|
5
|
0
|
3
|
0
|
|
Treatment to Week 104
Administrative problems
|
3
|
1
|
0
|
0
|
|
Treatment to Week 104
Protocol Violation
|
1
|
1
|
1
|
0
|
|
Extension Period Weeks 109-156
Withdrawal by Subject
|
8
|
1
|
8
|
0
|
|
Extension Period Weeks 109-156
Lost to Follow-up
|
6
|
1
|
5
|
0
|
|
Extension Period Weeks 109-156
Administrative problems
|
3
|
0
|
1
|
0
|
|
Extension Period Weeks 109-156
Protocol Violation
|
2
|
1
|
0
|
0
|
Baseline Characteristics
Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept
Baseline characteristics by cohort
| Measure |
LdT Mono at Week 24
n=99 Participants
Patients who had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 continued to receive 600 mg telbivudine daily after Week 24
|
LdT+TDF at Week 24
n=22 Participants
Patients who were initially treated with telbivudine and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 600 mg telbivudine daily and additional 300 mg tenofovir after Week 24.
|
TDF Mono at Week 24
n=109 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
n=11 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
Total
n=241 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
< 30 years
|
17 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
39 Participants
n=31 Participants
|
|
Age, Customized
Between 30 and 50 years
|
56 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
59 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
135 Participants
n=31 Participants
|
|
Age, Customized
> 50 years
|
26 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
67 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
73 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
71 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
168 Participants
n=31 Participants
|
|
HBV DNA
|
5.887 log10 copies/mL)
STANDARD_DEVIATION 1.2862 • n=99 Participants
|
7.769 log10 copies/mL)
STANDARD_DEVIATION 1.2502 • n=107 Participants
|
5.838 log10 copies/mL)
STANDARD_DEVIATION 1.2464 • n=206 Participants
|
7.938 log10 copies/mL)
STANDARD_DEVIATION 1.0709 • n=7 Participants
|
5.887 log10 copies/mL)
STANDARD_DEVIATION 1.2862 • n=31 Participants
|
|
HBV DNA levels < or ≥ 7 log 10 copies/mL at baseline.
< 7 log 10 copies/mL
|
81 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
83 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
171 Participants
n=31 Participants
|
|
HBV DNA levels < or ≥ 7 log 10 copies/mL at baseline.
≥ 7 log 10 copies/mL
|
18 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
70 Participants
n=31 Participants
|
|
Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN)
≤ 1 × ULN
|
46 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
52 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
105 Participants
n=31 Participants
|
|
Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN)
> 1 × - < 2 × ULN
|
35 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
74 Participants
n=31 Participants
|
|
Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN)
2 × - < 5 × ULN
|
13 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
51 Participants
n=31 Participants
|
|
Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN)
5 × or more ULN
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
|
Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN)
≤ 1 × ULN
|
70 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
69 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
151 Participants
n=31 Participants
|
|
Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN)
> 1 × - < 2 × ULN
|
14 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
51 Participants
n=31 Participants
|
|
Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN)
2 × - < 5 × ULN
|
12 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
33 Participants
n=31 Participants
|
|
Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN)
5 × or more ULN
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: week 52Population: Roadmap intent-to-treat (rITT) population consisted of patients in the ITT population who did not discontinue before Wk 24 and did not receive add-on. The total of the mono and combination arms were analyzed.
The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the "treating missing as failure" analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as "missing data."
Outcome measures
| Measure |
LdT Overall
n=113 Participants
Ldt Mono and LdT + TDF combined
|
TDF Overall
n=117 Participants
TDF mono and TDF + LdT combined
|
LdT Overall
Ldt Mono and LdT + TDF combined
|
TDF Mono at Week 24
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
TDF Overall
TDF mono and TDF + LdT combined
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
Missing DNA data at Wk 52=failure
|
91.0 percentage of participants
|
95.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
Imputing +/- 7 days DNA for Wk 52
|
91.9 percentage of participants
|
95.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
Imputing LOCF DNA for Wk 52
|
95.4 percentage of participants
|
99.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
Imputing within +28d DNA for Wk 52
|
92.7 percentage of participants
|
95.0 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: week 24, 52, 104Population: Roadmap intent-to-treat (rITT) population was analyzed.
To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL), ALT normalization, HBsAg loss, HBsAg conversion, virologic breakthrough (VB) at study visit, cumulative VB by study defined study period, cumulative treatment-emergent resistance
Outcome measures
| Measure |
LdT Overall
n=92 Participants
Ldt Mono and LdT + TDF combined
|
TDF Overall
n=21 Participants
TDF mono and TDF + LdT combined
|
LdT Overall
n=113 Participants
Ldt Mono and LdT + TDF combined
|
TDF Mono at Week 24
n=106 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
n=11 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
TDF Overall
n=117 Participants
TDF mono and TDF + LdT combined
|
|---|---|---|---|---|---|---|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break Wk52-Wk104 LOCF
|
12.0 percentage of particiipants
Interval 6.1 to 20.4
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
9.7 percentage of particiipants
Interval 5.0 to 16.8
|
1.9 percentage of particiipants
Interval 0.2 to 6.6
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
1.7 percentage of particiipants
Interval 0.2 to 6.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break BLto Wk 104 LOCF
|
14.1 percentage of particiipants
Interval 7.7 to 23.0
|
4.8 percentage of particiipants
Interval 0.1 to 23.8
|
12.4 percentage of particiipants
Interval 6.6 to 19.9
|
1.9 percentage of particiipants
Interval 0.2 to 6.6
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
1.7 percentage of particiipants
Interval 0.2 to 6.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum tx emergent resistance Wk 52
|
3.3 percentage of particiipants
Interval 0.7 to 9.2
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
2.7 percentage of particiipants
Interval 0.6 to 7.6
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Ccum tx emergent resistance Wk 104
|
9.2 percentage of particiipants
Interval 4.1 to 17.3
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
7.4 percentage of particiipants
Interval 3.3 to 14.1
|
0 percentage of particiipants
Interval 0.0 to 3.5
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum tx emergent resist Wk52 LOCF
|
3.3 percentage of particiipants
Interval 0.7 to 9.2
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
2.7 percentage of particiipants
Interval 0.6 to 7.6
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum tx emergent resist Wk 104 LOCF
|
9.2 percentage of particiipants
Interval 4.1 to 17.3
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
7.4 percentage of particiipants
Interval 3.3 to 14.1
|
0 percentage of particiipants
Interval 0.0 to 3.5
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
<7 log at BL HBV DNA <300 Wk52
|
93.4 percentage of particiipants
Interval 85.3 to 97.8
|
75.0 percentage of particiipants
Interval 19.4 to 99.4
|
92.5 percentage of particiipants
Interval 84.4 to 97.2
|
95.0 percentage of particiipants
Interval 87.7 to 98.6
|
100.0 percentage of particiipants
Interval 29.2 to 100.0
|
95.2 percentage of particiipants
Interval 88.1 to 98.7
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
<7 log HBV DNA <300 Wk104
|
68.4 percentage of particiipants
Interval 56.7 to 78.6
|
50.0 percentage of particiipants
Interval 6.8 to 93.2
|
67.5 percentage of particiipants
Interval 56.1 to 77.6
|
76.3 percentage of particiipants
Interval 65.4 to 85.1
|
66.7 percentage of particiipants
Interval 9.4 to 99.2
|
75.9 percentage of particiipants
Interval 65.3 to 84.6
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
<7 log HBV DNA <300 Wk 52 LOCF
|
97.4 percentage of particiipants
Interval 90.8 to 99.7
|
100.0 percentage of particiipants
Interval 39.8 to 100.0
|
97.5 percentage of particiipants
Interval 91.3 to 99.7
|
100.0 percentage of particiipants
Interval 95.5 to 100.0
|
100.0 percentage of particiipants
Interval 29.2 to 100.0
|
100.0 percentage of particiipants
Interval 95.7 to 100.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
<7 log HBV DNA <300 Wk 104 LOCF
|
92.1 percentage of particiipants
Interval 83.6 to 97.0
|
100.0 percentage of particiipants
Interval 39.8 to 100.0
|
92.5 percentage of particiipants
Interval 84.4 to 97.2
|
98.8 percentage of particiipants
Interval 93.2 to 100.0
|
100.0 percentage of particiipants
Interval 29.2 to 100.0
|
98.8 percentage of particiipants
Interval 93.5 to 100.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBV DNA <300 Week 24
|
98.9 percentage of particiipants
Interval 94.1 to 100.0
|
0.0 percentage of particiipants
Interval 0.0 to 16.1
|
80.5 percentage of particiipants
Interval 72.0 to 87.4
|
99.1 percentage of particiipants
Interval 94.9 to 100.0
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
89.7 percentage of particiipants
Interval 82.8 to 94.6
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBV DNA <300 Week 104
|
69.6 percentage of particiipants
Interval 59.1 to 78.7
|
76.2 percentage of particiipants
Interval 52.8 to 91.8
|
70.8 percentage of particiipants
Interval 61.5 to 79.0
|
74.5 percentage of particiipants
Interval 65.1 to 82.5
|
81.8 percentage of particiipants
Interval 48.2 to 97.7
|
75.2 percentage of particiipants
Interval 66.4 to 82.7
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBV DNA <300 Week 24 LOCF
|
100.0 percentage of particiipants
Interval 96.1 to 100.0
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
81.4 percentage of particiipants
Interval 73.0 to 88.1
|
100.0 percentage of particiipants
Interval 96.6 to 100.0
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
90.6 percentage of particiipants
Interval 83.8 to 95.2
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBV DNA <300 Wk104 LOCF
|
92.4 percentage of particiipants
Interval 84.9 to 96.9
|
100.0 percentage of particiipants
Interval 83.9 to 100.0
|
93.8 percentage of particiipants
Interval 87.7 to 97.5
|
99.1 percentage of particiipants
Interval 94.9 to 100.0
|
100.0 percentage of particiipants
Interval 71.5 to 100.0
|
99.1 percentage of particiipants
Interval 95.3 to 100.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
ALT Normalization Wk 52
|
84.0 percentage of particiipants
Interval 70.9 to 92.8
|
83.3 percentage of particiipants
Interval 58.6 to 96.4
|
83.8 percentage of particiipants
Interval 72.9 to 91.6
|
82.5 percentage of particiipants
Interval 70.1 to 91.3
|
85.7 percentage of particiipants
Interval 42.1 to 99.6
|
82.8 percentage of particiipants
Interval 71.3 to 91.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
ALT Normalization Week 104
|
70.0 percentage of particiipants
Interval 55.4 to 82.1
|
72.2 percentage of particiipants
Interval 46.5 to 90.3
|
70.6 percentage of particiipants
Interval 58.3 to 81.0
|
61.4 percentage of particiipants
Interval 47.6 to 74.0
|
85.7 percentage of particiipants
Interval 42.1 to 99.6
|
64.1 percentage of particiipants
Interval 51.1 to 75.7
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
ALT Normalization Wk 52 LOCF
|
88.0 percentage of particiipants
Interval 75.7 to 95.5
|
83.3 percentage of particiipants
Interval 58.6 to 96.4
|
86.8 percentage of particiipants
Interval 76.4 to 93.8
|
87.7 percentage of particiipants
Interval 76.3 to 94.9
|
85.7 percentage of particiipants
Interval 42.1 to 99.6
|
87.5 percentage of particiipants
Interval 76.8 to 94.4
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
ALT Normalization Wk 104 LOCF
|
92.0 percentage of particiipants
Interval 80.8 to 97.8
|
83.3 percentage of particiipants
Interval 58.6 to 96.4
|
89.7 percentage of particiipants
Interval 79.9 to 95.8
|
86.0 percentage of particiipants
Interval 74.2 to 93.7
|
85.7 percentage of particiipants
Interval 42.1 to 99.6
|
85.9 percentage of particiipants
Interval 75.0 to 93.4
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBsAg loss Week 52
|
0 percentage of particiipants
Interval 0.0 to 3.9
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
0 percentage of particiipants
Interval 0.0 to 3.2
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBsAg loss Week 104
|
0 percentage of particiipants
Interval 0.0 to 3.9
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
0 percentage of particiipants
Interval 0.0 to 3.2
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBsAg conversion Week 52
|
0 percentage of particiipants
Interval 0.0 to 3.9
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
0 percentage of particiipants
Interval 0.0 to 3.2
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
HBsAg conversion Week 104
|
0 percentage of particiipants
Interval 0.0 to 3.9
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
0 percentage of particiipants
Interval 0.0 to 3.2
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break BaseL to Wk 24
|
0 percentage of particiipants
Interval 0.0 to 3.9
|
4.8 percentage of particiipants
Interval 0.1 to 23.8
|
0.9 percentage of particiipants
Interval 0.0 to 4.8
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break Wk 24 to Wk 52
|
3.3 percentage of particiipants
Interval 0.7 to 9.2
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
2.7 percentage of particiipants
Interval 0.6 to 7.6
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break Wk 52 to Wk 104
|
12.0 percentage of particiipants
Interval 6.1 to 20.4
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
9.7 percentage of particiipants
Interval 5.0 to 16.8
|
1.9 percentage of particiipants
Interval 0.2 to 6.6
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
1.7 percentage of particiipants
Interval 0.2 to 6.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break BaseLto Wk 104
|
14.1 percentage of particiipants
Interval 7.7 to 23.0
|
4.8 percentage of particiipants
Interval 0.1 to 23.8
|
12.4 percentage of particiipants
Interval 6.9 to 19.9
|
1.9 percentage of particiipants
Interval 0.2 to 6.6
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
1.7 percentage of particiipants
Interval 0.2 to 6.0
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum vir break BL to Wk24 LOCF
|
0 percentage of particiipants
Interval 0.0 to 3.9
|
4.8 percentage of particiipants
Interval 0.1 to 23.8
|
0.9 percentage of particiipants
Interval 0.0 to 4.8
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
|
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Cum virol break Wk 24 to Wk 52 LOCF
|
3.3 percentage of particiipants
Interval 0.7 to 9.2
|
0 percentage of particiipants
Interval 0.0 to 16.1
|
2.7 percentage of particiipants
Interval 0.6 to 7.6
|
0 percentage of particiipants
Interval 0.0 to 3.4
|
0 percentage of particiipants
Interval 0.0 to 28.5
|
0 percentage of particiipants
Interval 0.0 to 3.1
|
SECONDARY outcome
Timeframe: 156 weeksPopulation: The modified ITT (mITT) population consisted of all patients in ITT population who were eligible and enrolled into the extension.
To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL) at Week156, ALT normalization, HBsAg loss, development of HBsAg conversion , cumulative tx emergent resistance, HBV DNA \<300 copies/mL with HBV DNA \<7 log at Baseline
Outcome measures
| Measure |
LdT Overall
n=62 Participants
Ldt Mono and LdT + TDF combined
|
TDF Overall
n=17 Participants
TDF mono and TDF + LdT combined
|
LdT Overall
n=79 Participants
Ldt Mono and LdT + TDF combined
|
TDF Mono at Week 24
n=79 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
n=10 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
TDF Overall
n=89 Participants
TDF mono and TDF + LdT combined
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
HBV DNA < 300 Week 156
|
17.7 percentage of participants
Interval 9.2 to 29.5
|
11.8 percentage of participants
Interval 1.5 to 36.4
|
16.5 percentage of participants
Interval 9.1 to 26.5
|
13.9 percentage of participants
Interval 7.2 to 23.5
|
20.0 percentage of participants
Interval 2.5 to 55.6
|
14.6 percentage of participants
Interval 8.0 to 23.7
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
HBV DNA < 300 Wk156 LOCF
|
88.7 percentage of participants
Interval 78.1 to 95.3
|
100.0 percentage of participants
Interval 80.5 to 100.0
|
91.1 percentage of participants
Interval 82.6 to 96.4
|
100.0 percentage of participants
Interval 95.4 to 100.0
|
100.0 percentage of participants
Interval 69.2 to 100.0
|
100.00 percentage of participants
Interval 95.9 to 100.0
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
ALT normalization Wk 156
|
14.3 percentage of participants
Interval 4.8 to 30.3
|
6.7 percentage of participants
Interval 0.2 to 31.9
|
12.0 percentage of participants
Interval 4.5 to 24.3
|
10.5 percentage of participants
Interval 2.9 to 24.8
|
28.6 percentage of participants
Interval 3.7 to 71.0
|
13.3 percentage of participants
Interval 5.1 to 26.8
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
ALT normalization Wk 156 LOCF
|
85.7 percentage of participants
Interval 69.7 to 95.2
|
93.3 percentage of participants
Interval 68.1 to 99.8
|
88.0 percentage of participants
Interval 75.7 to 95.5
|
86.8 percentage of participants
Interval 71.9 to 95.6
|
85.7 percentage of participants
Interval 42.1 to 99.6
|
86.7 percentage of participants
Interval 73.2 to 94.9
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
HBSAg loss/ seroconversion
|
0 percentage of participants
Interval 0.0 to 5.8
|
0 percentage of participants
Interval 0.0 to 19.5
|
0 percentage of participants
Interval 0.0 to 4.6
|
0 percentage of participants
Interval 0.0 to 4.6
|
0 percentage of participants
Interval 0.0 to 30.8
|
0 percentage of participants
Interval 0.0 to 4.1
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
Cum VB Wk104-156 LOCF
|
16.1 percentage of participants
Interval 8.0 to 27.7
|
0 percentage of participants
Interval 0.0 to 19.5
|
12.7 percentage of participants
Interval 6.2 to 22.0
|
1.3 percentage of participants
Interval 0.0 to 6.9
|
0 percentage of participants
Interval 0.0 to 30.8
|
1.1 percentage of participants
Interval 0.0 to 6.1
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
Cum VB BL to Wk 156 LOCF
|
21.0 percentage of participants
Interval 11.7 to 33.2
|
0 percentage of participants
Interval 0.0 to 19.5
|
16.5 percentage of participants
Interval 9.1 to 26.5
|
1.3 percentage of participants
Interval 0.0 to 6.9
|
0 percentage of participants
Interval 0.0 to 30.8
|
1.1 percentage of participants
Interval 0.0 to 6.1
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
Cum tx emerg resist Week 156 LOCF
|
14.0 percentage of participants
Interval 6.3 to 25.8
|
0 percentage of participants
Interval 0.0 to 19.5
|
10.8 percentage of participants
Interval 4.8 to 20.2
|
0 percentage of participants
Interval 0.0 to 4.6
|
0 percentage of participants
Interval 0.0 to 30.8
|
0 percentage of participants
Interval 0.0 to 4.1
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
HBV DNA < 300 Wk156 <7 log at BL
|
17.6 percentage of participants
Interval 8.4 to 30.9
|
0 percentage of participants
Interval 0.0 to 70.8
|
16.7 percentage of participants
Interval 7.9 to 29.3
|
11.7 percentage of participants
Interval 4.8 to 22.6
|
50.0 percentage of participants
Interval 1.3 to 98.7
|
12.9 percentage of participants
Interval 5.7 to 23.9
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
HBV DNA <300 Wk156 <7 log LOCF
|
88.2 percentage of participants
Interval 76.1 to 95.6
|
100.0 percentage of participants
Interval 29.2 to 100.0
|
88.9 percentage of participants
Interval 77.4 to 95.8
|
100.0 percentage of participants
Interval 94.0 to 100.0
|
100.0 percentage of participants
Interval 15.8 to 100.0
|
100.0 percentage of participants
Interval 94.2 to 100.0
|
|
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
Cum tx-emerg resist Wk156 <7log LOCF
|
8.7 percentage of participants
Interval 2.4 to 20.8
|
0.0 percentage of participants
Interval 0.0 to 70.8
|
8.2 percentage of participants
Interval 2.3 to 19.6
|
0.0 percentage of participants
Interval 0.0 to 6.0
|
0.0 percentage of participants
Interval 0.0 to 84.2
|
0.0 percentage of participants
Interval 0.0 to 5.8
|
SECONDARY outcome
Timeframe: Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeksPopulation: Safety population consisted of patients who received at least 1 dose of study drug and had 1 post-baseline safety assessment. Numbers in parentheses represent the number of participants who met the criteria for the measurement in the 2 LDT arms, LDT Overall, 2 TDF arms, TDF Overall, respectively
eGFR changes were calculated using the Modification of Diet in Renal Disease (MDRD) formula: GFR = 186 x (sCr)\^(-1.154) x (age)\^-0.203 with Female: Multiply GFR by 0.742; Black: Multiply GFR by 1.210. sCr is Serum Creatinine in mg/dl (measured at each scheduled visit). Age in years at visit (=\[sCr sample collection date -Date of birth\]/365.25). Weight in kilograms, as measured at the visit or the closest previous visit Safety population.
Outcome measures
| Measure |
LdT Overall
n=98 Participants
Ldt Mono and LdT + TDF combined
|
TDF Overall
n=22 Participants
TDF mono and TDF + LdT combined
|
LdT Overall
n=120 Participants
Ldt Mono and LdT + TDF combined
|
TDF Mono at Week 24
n=109 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24.
|
TDF + LdT at Week 24
n=11 Participants
Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24.
|
TDF Overall
n=120 Participants
TDF mono and TDF + LdT combined
|
|---|---|---|---|---|---|---|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 24 change (97,22,119,108,11,119)
|
1.43 mL/min/1.73 m2
Standard Deviation 12.815
|
-12.06 mL/min/1.73 m2
Standard Deviation 14.394
|
-1.07 mL/min/1.73 m2
Standard Deviation 14.076
|
-2.41 mL/min/1.73 m2
Standard Deviation 14.885
|
-7.17 mL/min/1.73 m2
Standard Deviation 15.368
|
-2.85 mL/min/1.73 m2
Standard Deviation 14.928
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 52 change(97,22,119,108,11,119)
|
5.18 mL/min/1.73 m2
Standard Deviation 18.842
|
-6.80 mL/min/1.73 m2
Standard Deviation 17.229
|
2.96 mL/min/1.73 m2
Standard Deviation 19.064
|
-2.70 mL/min/1.73 m2
Standard Deviation 18.636
|
-8.39 mL/min/1.73 m2
Standard Deviation 10.479
|
-3.22 mL/min/1.73 m2
Standard Deviation 18.082
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 104 change(97,22,119,108,11,119)
|
5.19 mL/min/1.73 m2
Standard Deviation 16.583
|
-5.77 mL/min/1.73 m2
Standard Deviation 15.943
|
3.16 mL/min/1.73 m2
Standard Deviation 16.947
|
-3.83 mL/min/1.73 m2
Standard Deviation 15.157
|
-8.69 mL/min/1.73 m2
Standard Deviation 15.632
|
-4.28 mL/min/1.73 m2
Standard Deviation 15.200
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 156 change(62,17,79,79,10,89)
|
8.07 mL/min/1.73 m2
Standard Deviation 16.777
|
-10.89 mL/min/1.73 m2
Standard Deviation 14.993
|
3.99 mL/min/1.73 m2
Standard Deviation 18.104
|
-5.34 mL/min/1.73 m2
Standard Deviation 13.393
|
-6.67 mL/min/1.73 m2
Standard Deviation 11.905
|
-5.49 mL/min/1.73 m2
Standard Deviation 13.178
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Baseline actual(98,22,120,109,11,120)
|
94.71 mL/min/1.73 m2
Standard Deviation 16.422
|
109.79 mL/min/1.73 m2
Standard Deviation 19.560
|
97.47 mL/min/1.73 m2
Standard Deviation 17.936
|
95.91 mL/min/1.73 m2
Standard Deviation 16.396
|
94.50 mL/min/1.73 m2
Standard Deviation 17.558
|
95.78 mL/min/1.73 m2
Standard Deviation 16.433
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 24 actual(97,22,119,108,11,119)
|
96.43 mL/min/1.73 m2
Standard Deviation 16.434
|
97.73 mL/min/1.73 m2
Standard Deviation 17.690
|
96.67 mL/min/1.73 m2
Standard Deviation 16.603
|
93.61 mL/min/1.73 m2
Standard Deviation 18.500
|
87.33 mL/min/1.73 m2
Standard Deviation 16.854
|
93.03 mL/min/1.73 m2
Standard Deviation 18.378
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 52 actual(97,22,119,108,11,119)
|
100.18 mL/min/1.73 m2
Standard Deviation 20.257
|
102.99 mL/min/1.73 m2
Standard Deviation 19.425
|
100.70 mL/min/1.73 m2
Standard Deviation 20.054
|
93.32 mL/min/1.73 m2
Standard Deviation 18.880
|
86.12 mL/min/1.73 m2
Standard Deviation 14.233
|
92.66 mL/min/1.73 m2
Standard Deviation 18.569
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 104 actual (97,22,119,108,11,119)
|
100.20 mL/min/1.73 m2
Standard Deviation 16.287
|
104.02 mL/min/1.73 m2
Standard Deviation 18.201
|
100.90 mL/min/1.73 m2
Standard Deviation 16.643
|
92.19 mL/min/1.73 m2
Standard Deviation 18.240
|
85.81 mL/min/1.73 m2
Standard Deviation 13.099
|
91.60 mL/min/1.73 m2
Standard Deviation 17.879
|
|
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Week 156 actual(62,17,79,79,10,89)
|
101.33 mL/min/1.73 m2
Standard Deviation 18.505
|
100.70 mL/min/1.73 m2
Standard Deviation 20.029
|
101.20 mL/min/1.73 m2
Standard Deviation 18.712
|
88.83 mL/min/1.73 m2
Standard Deviation 16.773
|
87.93 mL/min/1.73 m2
Standard Deviation 13.280
|
88.73 mL/min/1.73 m2
Standard Deviation 16.355
|
Adverse Events
LdT Mono at Week 24
Serious events: 6 serious events
Other events: 60 other events
Deaths: 0 deaths
LdT + TDF at Week 24
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
TDF Mono at Week 24
Serious events: 11 serious events
Other events: 56 other events
Deaths: 0 deaths
TDF + LdT at Week 24
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LdT Mono at Week 24
n=98 participants at risk
LdT Mono at Week 24
|
LdT + TDF at Week 24
n=22 participants at risk
LdT + TDF at Week 24
|
TDF Mono at Week 24
n=109 participants at risk
TDF Mono at Week 24
|
TDF + LdT at Week 24
n=11 participants at risk
TDF + LdT at Week 24
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/98
|
0.00%
0/22
|
1.8%
2/109
|
0.00%
0/11
|
|
Gastrointestinal disorders
Gastroduodenitis
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
General disorders
Fatigue
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Hepatobiliary disorders
Cholecystitis acute
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/98
|
0.00%
0/22
|
2.8%
3/109
|
0.00%
0/11
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Infections and infestations
Abdominal abscess
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Infections and infestations
Anal abscess
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Infections and infestations
Appendicitis
|
0.00%
0/98
|
4.5%
1/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Metabolism and nutrition disorders
Type 1 diabetes mellitus
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/98
|
4.5%
1/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
2.0%
2/98
|
0.00%
0/22
|
2.8%
3/109
|
0.00%
0/11
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to abdominal wall
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.00%
0/98
|
4.5%
1/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Psychiatric disorders
Psychogenic pain disorder
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/98
|
4.5%
1/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous
|
0.00%
0/98
|
4.5%
1/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Vascular disorders
Arterial occlusive disease
|
0.00%
0/98
|
4.5%
1/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Vascular disorders
Thrombophlebitis
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
0.00%
0/11
|
Other adverse events
| Measure |
LdT Mono at Week 24
n=98 participants at risk
LdT Mono at Week 24
|
LdT + TDF at Week 24
n=22 participants at risk
LdT + TDF at Week 24
|
TDF Mono at Week 24
n=109 participants at risk
TDF Mono at Week 24
|
TDF + LdT at Week 24
n=11 participants at risk
TDF + LdT at Week 24
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
18.2%
2/11
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.0%
2/98
|
0.00%
0/22
|
5.5%
6/109
|
0.00%
0/11
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Eye disorders
Visual impairment
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/98
|
4.5%
1/22
|
1.8%
2/109
|
9.1%
1/11
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.1%
6/98
|
0.00%
0/22
|
4.6%
5/109
|
27.3%
3/11
|
|
Gastrointestinal disorders
Diarrhoea
|
8.2%
8/98
|
0.00%
0/22
|
4.6%
5/109
|
0.00%
0/11
|
|
Gastrointestinal disorders
Dyspepsia
|
3.1%
3/98
|
0.00%
0/22
|
4.6%
5/109
|
9.1%
1/11
|
|
Gastrointestinal disorders
Gastritis
|
6.1%
6/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Gastrointestinal disorders
Nausea
|
10.2%
10/98
|
13.6%
3/22
|
1.8%
2/109
|
27.3%
3/11
|
|
Gastrointestinal disorders
Toothache
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
General disorders
Asthenia
|
5.1%
5/98
|
4.5%
1/22
|
0.00%
0/109
|
18.2%
2/11
|
|
General disorders
Fatigue
|
5.1%
5/98
|
4.5%
1/22
|
7.3%
8/109
|
0.00%
0/11
|
|
General disorders
Influenza like illness
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
General disorders
Oedema peripheral
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
18.2%
2/11
|
|
General disorders
Pyrexia
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Infections and infestations
Bronchitis
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Infections and infestations
Ear infection
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Infections and infestations
Influenza
|
8.2%
8/98
|
9.1%
2/22
|
7.3%
8/109
|
18.2%
2/11
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
7/98
|
9.1%
2/22
|
7.3%
8/109
|
9.1%
1/11
|
|
Infections and infestations
Respiratory tract infection
|
3.1%
3/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Infections and infestations
Rhinitis
|
5.1%
5/98
|
9.1%
2/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Injury, poisoning and procedural complications
Epicondylitis
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Injury, poisoning and procedural complications
Laceration
|
2.0%
2/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Investigations
Alanine aminotransferase increased
|
5.1%
5/98
|
0.00%
0/22
|
4.6%
5/109
|
9.1%
1/11
|
|
Investigations
Amylase increased
|
1.0%
1/98
|
9.1%
2/22
|
0.00%
0/109
|
0.00%
0/11
|
|
Investigations
Aspartate aminotransferase increased
|
7.1%
7/98
|
4.5%
1/22
|
3.7%
4/109
|
0.00%
0/11
|
|
Investigations
Blood creatine phosphokinase increased
|
24.5%
24/98
|
45.5%
10/22
|
15.6%
17/109
|
18.2%
2/11
|
|
Investigations
Blood phosphorus increased
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.1%
3/98
|
13.6%
3/22
|
7.3%
8/109
|
18.2%
2/11
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.2%
10/98
|
9.1%
2/22
|
1.8%
2/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.1%
4/98
|
0.00%
0/22
|
0.92%
1/109
|
18.2%
2/11
|
|
Nervous system disorders
Ataxia
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Nervous system disorders
Headache
|
17.3%
17/98
|
13.6%
3/22
|
14.7%
16/109
|
18.2%
2/11
|
|
Nervous system disorders
Paraesthesia
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Psychiatric disorders
Anxiety
|
1.0%
1/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Psychiatric disorders
Depression
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
18.2%
2/11
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Renal and urinary disorders
Crystalluria
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Renal and urinary disorders
Haematuria
|
1.0%
1/98
|
22.7%
5/22
|
0.92%
1/109
|
0.00%
0/11
|
|
Renal and urinary disorders
Nephroptosis
|
0.00%
0/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
1.0%
1/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.0%
2/98
|
0.00%
0/22
|
0.00%
0/109
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
|
Vascular disorders
Hypertension
|
7.1%
7/98
|
18.2%
4/22
|
4.6%
5/109
|
0.00%
0/11
|
|
Vascular disorders
Hypotension
|
0.00%
0/98
|
0.00%
0/22
|
0.92%
1/109
|
9.1%
1/11
|
Additional Information
Clinical Disclosure Office
Novartis
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place