Trial Outcomes & Findings for Belatacept in Liver Transplant Recipients (NCT NCT00555321)
NCT ID: NCT00555321
Last Updated: 2012-10-18
Results Overview
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N\>=5, otherwise exact method is used.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
260 participants
Primary outcome timeframe
At 6 months posttransplant
Results posted on
2012-10-18
Participant Flow
Participant milestones
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Treatment Phase up to 12-months
STARTED
|
52
|
51
|
50
|
53
|
54
|
|
Treatment Phase up to 12-months
Received Transplant and Treated
|
50
|
48
|
49
|
53
|
50
|
|
Treatment Phase up to 12-months
COMPLETED
|
31
|
29
|
26
|
46
|
32
|
|
Treatment Phase up to 12-months
NOT COMPLETED
|
21
|
22
|
24
|
7
|
22
|
|
Long-term Extension Phase
STARTED
|
30
|
27
|
24
|
38
|
26
|
|
Long-term Extension Phase
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Long-term Extension Phase
NOT COMPLETED
|
30
|
27
|
24
|
38
|
26
|
Reasons for withdrawal
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Treatment Phase up to 12-months
Adverse Event
|
6
|
7
|
11
|
7
|
18
|
|
Treatment Phase up to 12-months
Withdrawal by Subject
|
1
|
0
|
1
|
0
|
0
|
|
Treatment Phase up to 12-months
Death
|
2
|
1
|
4
|
0
|
0
|
|
Treatment Phase up to 12-months
Lack of Efficacy
|
9
|
8
|
5
|
0
|
0
|
|
Treatment Phase up to 12-months
Other Reason
|
1
|
3
|
2
|
0
|
0
|
|
Treatment Phase up to 12-months
Never treated
|
2
|
3
|
1
|
0
|
4
|
|
Long-term Extension Phase
Adverse Event
|
2
|
5
|
2
|
1
|
0
|
|
Long-term Extension Phase
Withdrawal by Subject
|
2
|
1
|
2
|
3
|
2
|
|
Long-term Extension Phase
Administrative reason by sponsor
|
23
|
21
|
18
|
31
|
23
|
|
Long-term Extension Phase
Death
|
2
|
0
|
0
|
3
|
0
|
|
Long-term Extension Phase
Participant did not meet study criteria
|
0
|
0
|
0
|
0
|
1
|
|
Long-term Extension Phase
Other Reason
|
1
|
0
|
2
|
0
|
0
|
Baseline Characteristics
Belatacept in Liver Transplant Recipients
Baseline characteristics by cohort
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
Total
n=250 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Customized
18 to 45 years
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
4 participants
n=5 Participants
|
11 participants
n=4 Participants
|
4 participants
n=21 Participants
|
33 participants
n=8 Participants
|
|
Age, Customized
46 to 65 years
|
41 participants
n=5 Participants
|
40 participants
n=7 Participants
|
43 participants
n=5 Participants
|
37 participants
n=4 Participants
|
42 participants
n=21 Participants
|
203 participants
n=8 Participants
|
|
Age, Customized
Above 65 years
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
5 participants
n=4 Participants
|
4 participants
n=21 Participants
|
14 participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
58 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
42 Participants
n=21 Participants
|
192 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
44 participants
n=5 Participants
|
40 participants
n=7 Participants
|
46 participants
n=5 Participants
|
49 participants
n=4 Participants
|
43 participants
n=21 Participants
|
222 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black / African American
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
2 participants
n=21 Participants
|
13 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
American Indian / Alaska native
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
1 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
3 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
5 participants
n=21 Participants
|
11 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino (US sites)
|
5 participants
n=5 Participants
|
7 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
4 participants
n=21 Participants
|
22 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino (US sites)
|
28 participants
n=5 Participants
|
16 participants
n=7 Participants
|
11 participants
n=5 Participants
|
22 participants
n=4 Participants
|
23 participants
n=21 Participants
|
100 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Unknown (Non- US sites)
|
17 participants
n=5 Participants
|
25 participants
n=7 Participants
|
35 participants
n=5 Participants
|
28 participants
n=4 Participants
|
23 participants
n=21 Participants
|
128 participants
n=8 Participants
|
|
Model for End-Stage Liver Disease (MELD) score
|
22.0 units on a scale
FULL_RANGE 8.19 • n=5 Participants
|
22.0 units on a scale
FULL_RANGE 8.29 • n=7 Participants
|
22.0 units on a scale
FULL_RANGE 6.05 • n=5 Participants
|
24.0 units on a scale
FULL_RANGE 7.48 • n=4 Participants
|
22.0 units on a scale
FULL_RANGE 5.48 • n=21 Participants
|
22.0 units on a scale
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Non-cholestatic cirrhosis
|
38 participants
n=5 Participants
|
33 participants
n=7 Participants
|
33 participants
n=5 Participants
|
39 participants
n=4 Participants
|
41 participants
n=21 Participants
|
184 participants
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Cholestatic liver disease cirrhosis
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
9 participants
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Biliary atresia
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
0 participants
n=21 Participants
|
1 participants
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Acute hepatic necrosis
|
4 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
1 participants
n=4 Participants
|
0 participants
n=21 Participants
|
8 participants
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Metabolic disease
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
0 participants
n=21 Participants
|
3 participants
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Malignant neoplasms
|
4 participants
n=5 Participants
|
7 participants
n=7 Participants
|
5 participants
n=5 Participants
|
6 participants
n=4 Participants
|
3 participants
n=21 Participants
|
25 participants
n=8 Participants
|
|
Primary cause of End Stage Liver Disease (ESLD)
Other
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
4 participants
n=4 Participants
|
4 participants
n=21 Participants
|
20 participants
n=8 Participants
|
|
United Network for Organ Sharing (UNOS) Status
Status 1
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
1 participants
n=8 Participants
|
|
United Network for Organ Sharing (UNOS) Status
Status 2A
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
0 participants
n=21 Participants
|
7 participants
n=8 Participants
|
|
United Network for Organ Sharing (UNOS) Status
Status 2B
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
13 participants
n=8 Participants
|
|
United Network for Organ Sharing (UNOS) Status
Status 3
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
8 participants
n=8 Participants
|
|
United Network for Organ Sharing (UNOS) Status
Not available
|
44 participants
n=5 Participants
|
42 participants
n=7 Participants
|
40 participants
n=5 Participants
|
48 participants
n=4 Participants
|
47 participants
n=21 Participants
|
221 participants
n=8 Participants
|
|
Participants on Anti-Hypertensive Medications
No
|
41 participants
n=5 Participants
|
39 participants
n=7 Participants
|
41 participants
n=5 Participants
|
42 participants
n=4 Participants
|
40 participants
n=21 Participants
|
203 participants
n=8 Participants
|
|
Participants on Anti-Hypertensive Medications
Yes
|
9 participants
n=5 Participants
|
9 participants
n=7 Participants
|
8 participants
n=5 Participants
|
11 participants
n=4 Participants
|
10 participants
n=21 Participants
|
47 participants
n=8 Participants
|
|
Participants on Lipid Lowering Medications
No
|
46 participants
n=5 Participants
|
43 participants
n=7 Participants
|
48 participants
n=5 Participants
|
51 participants
n=4 Participants
|
44 participants
n=21 Participants
|
232 participants
n=8 Participants
|
|
Participants on Lipid Lowering Medications
Yes
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
6 participants
n=21 Participants
|
18 participants
n=8 Participants
|
|
Participants on Anti-diabetic Medications
No
|
35 participants
n=5 Participants
|
35 participants
n=7 Participants
|
40 participants
n=5 Participants
|
41 participants
n=4 Participants
|
38 participants
n=21 Participants
|
189 participants
n=8 Participants
|
|
Participants on Anti-diabetic Medications
Yes
|
15 participants
n=5 Participants
|
13 participants
n=7 Participants
|
9 participants
n=5 Participants
|
12 participants
n=4 Participants
|
12 participants
n=21 Participants
|
61 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: At 6 months posttransplantPopulation: Intent-to-Treat (ITT) population: all randomized and transplanted participants.
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N\>=5, otherwise exact method is used.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant
|
48.0 percentage of participants
Interval 34.2 to 61.8
|
41.7 percentage of participants
Interval 27.7 to 55.6
|
46.9 percentage of participants
Interval 33.0 to 60.9
|
15.1 percentage of participants
Interval 5.5 to 24.7
|
38.0 percentage of participants
Interval 24.5 to 51.5
|
PRIMARY outcome
Timeframe: Day 1 (randomization) to Week 104 + within 56 Days after the last infusion/dose, Deaths were monitored up to database lock (20-June-2011)Population: ITT-LTE population, (all randomized and transplanted participants who entered long term extension). Participants were grouped according to the treatment to which they were randomized initially.
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
SAEs
|
18 participants
|
22 participants
|
17 participants
|
29 participants
|
21 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
Related SAEs
|
5 participants
|
9 participants
|
9 participants
|
12 participants
|
9 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
Discontinued due to SAEs
|
2 participants
|
4 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
AEs
|
30 participants
|
27 participants
|
23 participants
|
38 participants
|
26 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
Related AEs
|
27 participants
|
21 participants
|
20 participants
|
33 participants
|
23 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
Discontinued due to AEs
|
2 participants
|
5 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
Deaths (due to AE)
|
2 participants
|
3 participants
|
1 participants
|
3 participants
|
0 participants
|
|
Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)
Deaths (not due to AE)
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Day 1 (randomization) through database lock (20-June-2011)Population: ITT-LTE population, all randomized and transplanted participants who entered long term extension
AE of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial).
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Who Had AEs of Special Interest During the LTE
Malignancies
|
1 participants
|
4 participants
|
3 participants
|
8 participants
|
3 participants
|
|
Number of Participants Who Had AEs of Special Interest During the LTE
Infections and Infestations
|
8 participants
|
6 participants
|
9 participants
|
11 participants
|
8 participants
|
PRIMARY outcome
Timeframe: Every 4 weeks from Week 53 to Week 104.Population: ITT-LTE population: All randomized and transplanted participants who entered long-term extension. n= participants who had a laboratory test reading after transplant for the specific analyte.
Low platelet count: \<50\*10\^9 c/µl; Low leukocytes: \<2.0\*10\^3 c/µl; Low lymphocytes (absolute): \<0.5\*10\^3 c/µl; Low neutrophils (absolute): \<1.0\*10\^3 c/µl.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Hematology Abnormalities During the LTE
Low Platelets: (n=29, 26, 22, 37, 25)
|
1 participants
|
2 participants
|
0 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Marked Hematology Abnormalities During the LTE
Low Leukocytes : (n=29, 27, 22, 37, 25)
|
1 participants
|
2 participants
|
0 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Marked Hematology Abnormalities During the LTE
Low Absolute Lymphocyte: (n=29, 27, 22, 36, 25)
|
8 participants
|
3 participants
|
3 participants
|
5 participants
|
3 participants
|
|
Number of Participants With Marked Hematology Abnormalities During the LTE
Low Absolute Neutrophils: (n=29, 27, 22, 36, 25)
|
0 participants
|
2 participants
|
1 participants
|
2 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Every 4 weeks from Week 53 to Week 104.Population: ITT-LTE population: All randomized and transplanted participants who entered long-term extension. n= participants who had a laboratory test reading after transplant for the specific analyte.
ULN= upper limit of normal; Normal ranges are provided by the Central Laboratory and may vary according to sex and age. High alanine aminotransferase (ALT): \>5.0\*ULN U/L; High aspartate aminotransferase (AST): \>5.0\*ULN U/L; High direct bilirubin: \>3.0\*ULN mg/dL; High g-glutamyl transferase (GGT): \>5.0\*ULN U/L; High total bilirubin: \>3.0\*ULN mg/dL; High creatinine: \> 3.0\*ULN mg/dL
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=29 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=22 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=37 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=25 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE
High Direct Bilirubin
|
1 participants
|
4 participants
|
1 participants
|
3 participants
|
2 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE
High GGT
|
2 participants
|
6 participants
|
6 participants
|
13 participants
|
8 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE
High Total Bilirubin
|
1 participants
|
3 participants
|
1 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE
High Creatinine
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE
High ALT
|
0 participants
|
2 participants
|
1 participants
|
4 participants
|
3 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE
High AST
|
0 participants
|
3 participants
|
2 participants
|
4 participants
|
3 participants
|
PRIMARY outcome
Timeframe: Every 4 weeks from Week 53 to Week 104.Population: ITT-LTE population: All randomized and transplanted participants who entered long-term extension. n= participants who had a laboratory test reading after transplant for the specific analyte.
Low Serum Potassium: \<3.0 meq/L; High serum potassium:\>6.0 mEq/L; Low serum magnesium:\<0.8 mEq/L; Low serum sodium: \<130 mEq/L; High serum sodium: \>155 mEq/L; Low inorganic phosphorus: \<2.0 mg/dL; High uric acid: \>10 mg/dL
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=29 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=22 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=37 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=25 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
Low Serum Potassium
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
High Serum Potassium
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
High Uric Acid
|
0 participants
|
1 participants
|
0 participants
|
6 participants
|
6 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
Low Serum Sodium
|
1 participants
|
2 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
High Serum Sodium
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE
Low Inorganic Phosphorus
|
1 participants
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At 6 and 12 monthsPopulation: ITT population: all randomized and transplanted participants.
For 95% CI within each group, normal approximation was used if N\>=5. Otherwise exact method was used.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase
At 6 months
|
90.0 percentage of participants
Interval 81.7 to 98.3
|
89.6 percentage of participants
Interval 80.9 to 98.2
|
77.6 percentage of participants
Interval 65.9 to 89.2
|
92.5 percentage of participants
Interval 85.3 to 99.6
|
90.0 percentage of participants
Interval 81.7 to 98.3
|
|
Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase
At 12 months
|
90.0 percentage of participants
Interval 81.7 to 98.3
|
83.3 percentage of participants
Interval 72.8 to 93.9
|
67.3 percentage of participants
Interval 54.2 to 80.5
|
92.5 percentage of participants
Interval 85.3 to 99.6
|
88.0 percentage of participants
Interval 79.0 to 97.0
|
SECONDARY outcome
Timeframe: Day 1 (randomization) through database lock (20-June-2011)Population: ITT-LTE population, all randomized and transplanted participants who entered long term extension.
For 95% CI within each group, normal approximation was used if N\>=5, otherwise exact method was used.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data)
|
93.3 percentage of participants
Interval 84.4 to 100.0
|
85.2 percentage of participants
Interval 71.8 to 98.6
|
95.8 percentage of participants
Interval 87.8 to 100.0
|
92.1 percentage of participants
Interval 83.5 to 100.0
|
96.2 percentage of participants
Interval 88.8 to 100.0
|
SECONDARY outcome
Timeframe: At 12 months posttransplantPopulation: ITT population: all randomized and transplanted participants
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% CI within each group, normal approximation is used if N\>=5. Otherwise exact method is used. For 95% CI of difference, adjustment is made for randomization strata if N \>= 5 in each treatment arm.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months
|
52.0 percentage of participants
Interval 38.2 to 65.8
|
47.9 percentage of participants
Interval 33.8 to 62.0
|
53.1 percentage of participants
Interval 39.1 to 67.0
|
18.9 percentage of participants
Interval 8.3 to 29.4
|
40.0 percentage of participants
Interval 26.4 to 53.6
|
SECONDARY outcome
Timeframe: Day 1 (randomization) through database lock (20-June-2011)Population: ITT-LTE population: all randomized and transplanted participants who entered the Long term extension
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a central histopathologist using Banff criteria. For 95% CI within each group, normal approximation was used if N\>=5, otherwise exact method was used.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data)
|
36.7 percentage of participants
Interval 19.4 to 53.9
|
37.0 percentage of participants
Interval 18.8 to 55.3
|
25.0 percentage of participants
Interval 7.7 to 42.3
|
21.1 percentage of participants
Interval 8.1 to 34.0
|
23.1 percentage of participants
Interval 6.9 to 39.3
|
SECONDARY outcome
Timeframe: 3 , 6, and 12 monthsPopulation: ITT population: all randomized and transplanted participants
Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 3 months ; Overall
|
17 participants
|
15 participants
|
14 participants
|
4 participants
|
13 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 3 months ; 1 episode
|
15 participants
|
14 participants
|
14 participants
|
4 participants
|
12 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 3 months ; 2 episodes
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 3 months ; >2 episodes
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 6 months ; Overall
|
20 participants
|
15 participants
|
15 participants
|
5 participants
|
15 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 6 months ; 1 episode
|
18 participants
|
12 participants
|
14 participants
|
4 participants
|
13 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 6 months ; 2 episodes
|
1 participants
|
3 participants
|
1 participants
|
1 participants
|
2 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 6 months ; >2 episodes
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 12 months ; Overall
|
22 participants
|
16 participants
|
16 participants
|
7 participants
|
15 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 12 months ; 1 episode
|
18 participants
|
13 participants
|
14 participants
|
6 participants
|
13 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 12 months ; 2 episodes
|
3 participants
|
3 participants
|
2 participants
|
1 participants
|
2 participants
|
|
Number of Participants Having Acute Rejections: 12-month Treatment Phase
By 12 months ; >2 episodes
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1 (randomization) through database lock (20-June-2011)Population: ITT-LTE population, all randomized and transplanted participants who entered long-term extension
Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Having Acute Rejections During the LTE
By Database lock ; >2 episodes
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By 12 months (m); Overall
|
9 participants
|
6 participants
|
6 participants
|
6 participants
|
6 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By 12 m ; 1 episode
|
8 participants
|
6 participants
|
5 participants
|
5 participants
|
5 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By 12 m ; 2 episodes
|
1 participants
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By 12 m; >2 episodes
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By Database lock; Overall
|
9 participants
|
6 participants
|
6 participants
|
6 participants
|
6 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By Database lock ; 1 episode
|
8 participants
|
6 participants
|
5 participants
|
5 participants
|
5 participants
|
|
Number of Participants Having Acute Rejections During the LTE
By Database lock ; 2 episodes
|
1 participants
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 3, 6 and 12 months posttransplantPopulation: ITT population: all randomized and transplanted participants
Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. TRT= treatment
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Acute rejections
|
7 participants
|
15 participants
|
14 participants
|
4 participants
|
13 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Treated participants
|
10 participants
|
11 participants
|
7 participants
|
3 participants
|
10 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Corticosteroid treatment Only
|
10 participants
|
7 participants
|
7 participants
|
2 participants
|
9 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Corticosteroid resistant
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Refractory
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By3 months: Initial lymphocyte depleting TRT
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Increase in dose of Tacrolimus
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 3 months: Other / not available
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Acute rejections
|
20 participants
|
15 participants
|
15 participants
|
5 participants
|
15 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Treated participants
|
12 participants
|
11 participants
|
8 participants
|
4 participants
|
12 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Corticosteroid treatment Only
|
12 participants
|
6 participants
|
8 participants
|
3 participants
|
10 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Corticosteroid resistant
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Refractory
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Initial lymphocyte depleting TRT
|
0 participants
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Increase in dose of Tacrolimus
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 6 months: Other / not available
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 12 months: Acute rejections
|
22 participants
|
16 participants
|
16 participants
|
7 participants
|
15 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 12 months: Treated participants
|
12 participants
|
12 participants
|
8 participants
|
5 participants
|
2 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 12 months: Corticosteroid treatment Only
|
12 participants
|
7 participants
|
8 participants
|
4 participants
|
10 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 12 months: Corticosteroid resistant
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
By 12 months: Refractory
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
B12 months: Initial lymphocyte depleting TRT
|
0 participants
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months
12 months: Other / not available
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 1 (randomization) through database lock (20-June-2011)Population: ITT-LTE population, all randomized and transplanted participants who entered long term extension.
Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. DBL=database lock, TRT=treatment
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Acute rejections
|
9 participants
|
6 participants
|
6 participants
|
6 participants
|
6 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Treated participants
|
4 participants
|
5 participants
|
4 participants
|
5 participants
|
6 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Corticosteroid treatment Only
|
4 participants
|
4 participants
|
4 participants
|
4 participants
|
5 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Corticosteroid resistant
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Refractory
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Initial lymphocyte depleting TRT
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Other / not available
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By 12 months: Increase in dose of TAC
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Acute rejections
|
9 participants
|
6 participants
|
6 participants
|
6 participants
|
6 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Treated participants
|
4 participants
|
5 participants
|
4 participants
|
5 participants
|
6 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Corticosteroid treatment Only
|
4 participants
|
4 participants
|
4 participants
|
4 participants
|
5 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Corticosteroid resistant
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Refractory
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Initial lymphocyte depleting treatment
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Other/ Not available
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE
By DBL: Increase in dose of TAC
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 3, 6 and 12 months posttransplantPopulation: ITT population: all randomized and transplanted participants
Acute Rejections (AR) were clinically suspected and biopsy proven by central pathologist. The Banff grading is a classification of renal allograft pathology and AR. Grade I: AR requiring moderate (\>25%) to severe mononuclear cell interstitial infiltrate and moderate tubulitis; Grade II: AR requiring severe tubulitis and/or intimal arteritis; Grade III: AR requiring transmural arteritis. Only the episode with highest Banff grade for each participant was counted.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 3 months: Grade 1
|
14 participants
Interval 20.9 to 47.1
|
8 participants
Interval 18.1 to 44.4
|
7 participants
Interval 15.9 to 41.2
|
3 participants
Interval 2.1 to 18.2
|
6 participants
Interval 13.8 to 38.2
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 3 months: Grade 2
|
3 participants
Interval 26.4 to 53.6
|
6 participants
Interval 18.1 to 44.4
|
6 participants
Interval 17.7 to 43.5
|
1 participants
Interval 1.6 to 17.3
|
5 participants
Interval 17.3 to 42.7
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 3 months: Grade 3
|
0 participants
Interval 30.2 to 57.8
|
1 participants
Interval 20.0 to 46.7
|
1 participants
Interval 19.5 to 45.8
|
0 participants
Interval 4.1 to 22.3
|
2 participants
Interval 17.3 to 42.7
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 6 months: Grade 1
|
16 participants
|
6 participants
|
7 participants
|
4 participants
|
7 participants
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 6 months: Grade 2
|
4 participants
|
8 participants
|
7 participants
|
1 participants
|
6 participants
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 6 months: Grade 3
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
2 participants
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 12 months: Grade 1
|
15 participants
|
7 participants
|
7 participants
|
6 participants
|
7 participants
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 12 months: Grade 2
|
7 participants
|
8 participants
|
8 participants
|
1 participants
|
6 participants
|
|
Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months
By 12 months: Grade 3
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 3, 6 and 12 months posttransplantPopulation: ITT population: all randomized and transplanted participants
Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 3 months; Indeterminate score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 3 months; Mild Score
|
14 participants
|
8 participants
|
7 participants
|
3 participants
|
7 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 3 months; Moderate Score
|
3 participants
|
6 participants
|
7 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 3 months; Severe Score
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
4 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 6 months; Indeterminate score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 6 months; Mild Score
|
17 participants
|
6 participants
|
7 participants
|
4 participants
|
8 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 6 months; Moderate Score
|
3 participants
|
8 participants
|
8 participants
|
1 participants
|
3 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 6 months; Severe Score
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
4 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 12 months; Indeterminate score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 12 months; Mild Score
|
17 participants
|
7 participants
|
7 participants
|
6 participants
|
8 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 12 months; Moderate Score
|
4 participants
|
8 participants
|
9 participants
|
1 participants
|
3 participants
|
|
Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months
By 12 months; Severe Score
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
4 participants
|
SECONDARY outcome
Timeframe: Day 1 (randomization) through End of study (database lock of 20-June-2011)Population: ITT-LTE population, all randomized and transplanted participants who entered the long-term extension phase.
Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
By 12 months; Mild Score
|
8 participants
|
5 participants
|
2 participants
|
5 participants
|
4 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
At end of study; Mild Score
|
8 participants
|
5 participants
|
2 participants
|
5 participants
|
4 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
At end of study; Moderate Score
|
1 participants
|
1 participants
|
4 participants
|
1 participants
|
0 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
At end of study; Severe Score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
By 12 months; Indeterminate score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
By 12 months; Moderate Score
|
1 participants
|
1 participants
|
4 participants
|
1 participants
|
0 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
By 12 months; Severe Score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE
At end of study; Indeterminate score
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 3, 6, 9 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
The time from transplantation to the first AR episode in each treatment arm was summarized using Kaplan-Meier curves. Acute Rejections were clinically suspected and biopsy proven by central pathologist.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months
By 3 months
|
30 participants
|
31 participants
|
30 participants
|
48 participants
|
34 participants
|
|
Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months
By 6 months
|
27 participants
|
29 participants
|
28 participants
|
47 participants
|
32 participants
|
|
Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months
By 9 months
|
25 participants
|
29 participants
|
27 participants
|
47 participants
|
32 participants
|
|
Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months
By 12 months
|
23 participants
|
25 participants
|
23 participants
|
42 participants
|
28 participants
|
SECONDARY outcome
Timeframe: Baseline (2 month), 12 months posttransplantPopulation: ITT population: all randomized and transplanted subjects. n = participants who had both baseline and postbaseline values.
GFR was assessed using a true measure of glomerular filtration via iothalamate clearance test. The month 2 time point was selected as the "baseline" time point with respect to measured GFR due to logistical difficulty in obtaining measured GFR at the time of liver transplant and post-transplant renal function largely stabilizing by 2 months. All Measured GFR \> 200 were truncated at 200.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase
2 months (n=37, 36, 35, 41, 37)
|
72.4 mL/min/1.73m^2
Standard Deviation 29.50
|
86.6 mL/min/1.73m^2
Standard Deviation 37.38
|
98.6 mL/min/1.73m^2
Standard Deviation 41.89
|
65.9 mL/min/1.73m^2
Standard Deviation 35.52
|
58.5 mL/min/1.73m^2
Standard Deviation 33.96
|
|
Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase
12 months (n=39, 35, 29, 40, 32)
|
88.9 mL/min/1.73m^2
Standard Deviation 36.34
|
93.1 mL/min/1.73m^2
Standard Deviation 38.99
|
73.1 mL/min/1.73m^2
Standard Deviation 36.82
|
75.2 mL/min/1.73m^2
Standard Deviation 46.89
|
70.5 mL/min/1.73m^2
Standard Deviation 29.59
|
|
Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase
Change from 2 to 12 months (n=31, 29, 26, 36, 29)
|
14.2 mL/min/1.73m^2
Standard Deviation 40.64
|
5.8 mL/min/1.73m^2
Standard Deviation 48.20
|
-19.6 mL/min/1.73m^2
Standard Deviation 49.56
|
5.3 mL/min/1.73m^2
Standard Deviation 51.81
|
7.3 mL/min/1.73m^2
Standard Deviation 31.59
|
SECONDARY outcome
Timeframe: Baseline [BL] (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m\^2) = 170\*(Scr)\^-0.999\*(Age)\^-0.176\*(0.762 if female)\*(1.180 if African American)\*(BUN)\^-0.170\*(Alb)\^+0.318. ). BL= baseline, mL= milliliters; min= minute; m\^2= meters squared.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
BL; (n=47, 42, 42, 45, 45)
|
66.3 mL/min/1.73 m^2
Standard Deviation 29.14
|
77.4 mL/min/1.73 m^2
Standard Deviation 33.42
|
76.6 mL/min/1.73 m^2
Standard Deviation 27.77
|
73.7 mL/min/1.73 m^2
Standard Deviation 32.42
|
80.2 mL/min/1.73 m^2
Standard Deviation 30.78
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
1 month; (n=45, 44, 42, 49, 49)
|
85.6 mL/min/1.73 m^2
Standard Deviation 25.27
|
93.1 mL/min/1.73 m^2
Standard Deviation 35.66
|
89.6 mL/min/1.73 m^2
Standard Deviation 28.47
|
64.9 mL/min/1.73 m^2
Standard Deviation 26.31
|
62.2 mL/min/1.73 m^2
Standard Deviation 31.94
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
Change from BL to 1 month; (n=43, 38, 37, 41, 45)
|
21.0 mL/min/1.73 m^2
Standard Deviation 33.76
|
15.3 mL/min/1.73 m^2
Standard Deviation 44.72
|
11.4 mL/min/1.73 m^2
Standard Deviation 31.34
|
-8.7 mL/min/1.73 m^2
Standard Deviation 33.91
|
-17.7 mL/min/1.73 m^2
Standard Deviation 40.65
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
2 months; (n=29, 30, 23, 25, 27)
|
86.1 mL/min/1.73 m^2
Standard Deviation 21.78
|
96.6 mL/min/1.73 m^2
Standard Deviation 27.78
|
105.8 mL/min/1.73 m^2
Standard Deviation 31.98
|
76.3 mL/min/1.73 m^2
Standard Deviation 35.25
|
66.9 mL/min/1.73 m^2
Standard Deviation 28.42
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
Change from BL to 2 months; (n=28, 26, 20, 22, 25)
|
25.3 mL/min/1.73 m^2
Standard Deviation 32.35
|
18.3 mL/min/1.73 m^2
Standard Deviation 33.35
|
31.5 mL/min/1.73 m^2
Standard Deviation 26.89
|
-1.5 mL/min/1.73 m^2
Standard Deviation 52.78
|
-14.0 mL/min/1.73 m^2
Standard Deviation 34.03
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
3 months; (n=36, 36, 35, 46, 37)
|
86.5 mL/min/1.73 m^2
Standard Deviation 21.20
|
91.7 mL/min/1.73 m^2
Standard Deviation 26.83
|
96.6 mL/min/1.73 m^2
Standard Deviation 27.02
|
65.0 mL/min/1.73 m^2
Standard Deviation 19.93
|
60.4 mL/min/1.73 m^2
Standard Deviation 22.98
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
Change from BL to 3 months; (n=33, 34, 30, 40, 33)
|
22.0 mL/min/1.73 m^2
Standard Deviation 29.04
|
13.3 mL/min/1.73 m^2
Standard Deviation 31.50
|
18.3 mL/min/1.73 m^2
Standard Deviation 26.92
|
-8.4 mL/min/1.73 m^2
Standard Deviation 30.89
|
-20.2 mL/min/1.73 m^2
Standard Deviation 32.08
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
6 months; (n=39, 34, 38, 49, 36)
|
82.2 mL/min/1.73 m^2
Standard Deviation 23.88
|
90.3 mL/min/1.73 m^2
Standard Deviation 24.23
|
86.0 mL/min/1.73 m^2
Standard Deviation 28.74
|
61.9 mL/min/1.73 m^2
Standard Deviation 20.62
|
59.8 mL/min/1.73 m^2
Standard Deviation 22.37
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
Change from BL to 6 months; (n=37, 30, 33, 42, 31)
|
18.6 mL/min/1.73 m^2
Standard Deviation 31.06
|
7.6 mL/min/1.73 m^2
Standard Deviation 31.43
|
5.6 mL/min/1.73 m^2
Standard Deviation 26.78
|
-11.7 mL/min/1.73 m^2
Standard Deviation 30.61
|
-22.7 mL/min/1.73 m^2
Standard Deviation 29.63
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
12 months; (n=40, 33, 35, 46, 38)
|
83.8 mL/min/1.73 m^2
Standard Deviation 22.18
|
97.7 mL/min/1.73 m^2
Standard Deviation 23.80
|
85.6 mL/min/1.73 m^2
Standard Deviation 31.23
|
68.4 mL/min/1.73 m^2
Standard Deviation 26.09
|
63.8 mL/min/1.73 m^2
Standard Deviation 21.24
|
|
Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase
Change from BL to 12 month; (n=37, 29, 30, 41, 33)
|
18.2 mL/min/1.73 m^2
Standard Deviation 27.63
|
19.2 mL/min/1.73 m^2
Standard Deviation 30.05
|
4.2 mL/min/1.73 m^2
Standard Deviation 30.40
|
-6.3 mL/min/1.73 m^2
Standard Deviation 40.08
|
-17.1 mL/min/1.73 m^2
Standard Deviation 28.61
|
SECONDARY outcome
Timeframe: Baseline (pretransplant time point), 1, 2, 3, 6,12, 18, 24, 30, 36 months posttransplantPopulation: ITT-LTE population, all randomized and transplanted participants who entered long term extension. n= participants who have both baseline and postbaseline values.
GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m\^2) = 170\*(Scr)\^-0.999\*(Age)\^-0.176\*(0.762 if female)\*(1.180 if African American)\*(BUN)\^-0.170\*(Alb)\^+0.318. ). BL= baseline, mL= milliliters; min= minute; m\^2= meters squared.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=30 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=27 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=24 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=26 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 2 months; (n=20,19,14,17,18)
|
26.0 mL/min/1.73 m^2
Standard Deviation 34.74
|
12.6 mL/min/1.73 m^2
Standard Deviation 30.12
|
30.7 mL/min/1.73 m^2
Standard Deviation 29.13
|
-11.6 mL/min/1.73 m^2
Standard Deviation 36.28
|
-17.4 mL/min/1.73 m^2
Standard Deviation 33.94
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Baseline (BL); (n=27,24,20,33,23)
|
64.4 mL/min/1.73 m^2
Standard Deviation 32.98
|
85.6 mL/min/1.73 m^2
Standard Deviation 34.74
|
78.0 mL/min/1.73 m^2
Standard Deviation 31.65
|
77.9 mL/min/1.73 m^2
Standard Deviation 32.13
|
83.0 mL/min/1.73 m^2
Standard Deviation 35.80
|
|
Mean Change From Baseline in Calculated GFR During the LTE
1 month; (n=28,27,23,36,25)
|
88.2 mL/min/1.73 m^2
Standard Deviation 24.56
|
103.1 mL/min/1.73 m^2
Standard Deviation 38.89
|
95.1 mL/min/1.73 m^2
Standard Deviation 26.70
|
68.6 mL/min/1.73 m^2
Standard Deviation 28.06
|
59.1 mL/min/1.73 m^2
Standard Deviation 22.41
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 1 month; (n=26,24,20,31,23)
|
26.3 mL/min/1.73 m^2
Standard Deviation 30.52
|
20.2 mL/min/1.73 m^2
Standard Deviation 52.60
|
16.0 mL/min/1.73 m^2
Standard Deviation 31.53
|
-7.6 mL/min/1.73 m^2
Standard Deviation 37.19
|
-22.6 mL/min/1.73 m^2
Standard Deviation 25.62
|
|
Mean Change From Baseline in Calculated GFR During the LTE
2 months; (n=21,21,15,19,19)
|
86.2 mL/min/1.73 m^2
Standard Deviation 22.29
|
99.4 mL/min/1.73 m^2
Standard Deviation 29.58
|
102.3 mL/min/1.73 m^2
Standard Deviation 32.44
|
71.2 mL/min/1.73 m^2
Standard Deviation 18.88
|
64.4 mL/min/1.73 m^2
Standard Deviation 28.90
|
|
Mean Change From Baseline in Calculated GFR During the LTE
3 months; (n=27, 26, 24, 35, 24)
|
87.0 mL/min/1.73 m^2
Standard Deviation 22.30
|
97.0 mL/min/1.73 m^2
Standard Deviation 26.14
|
97.0 mL/min/1.73 m^2
Standard Deviation 25.94
|
66.5 mL/min/1.73 m^2
Standard Deviation 20.36
|
57.0 mL/min/1.73 m^2
Standard Deviation 22.61
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 3 months; (n=24, 24, 20, 30, 21)
|
23.3 mL/min/1.73 m^2
Standard Deviation 32.20
|
13.7 mL/min/1.73 m^2
Standard Deviation 32.38
|
17.0 mL/min/1.73 m^2
Standard Deviation 27.99
|
-8.1 mL/min/1.73 m^2
Standard Deviation 31.69
|
-23.5 mL/min/1.73 m^2
Standard Deviation 30.57
|
|
Mean Change From Baseline in Calculated GFR During the LTE
6 months; (n=29, 26, 24, 24, 38, 23)
|
87.6 mL/min/1.73 m^2
Standard Deviation 23.93
|
93.1 mL/min/1.73 m^2
Standard Deviation 23.45
|
92.3 mL/min/1.73 m^2
Standard Deviation 24.71
|
64.6 mL/min/1.73 m^2
Standard Deviation 20.43
|
56.7 mL/min/1.73 m^2
Standard Deviation 20.37
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 6 months; (n=27, 23, 20, 33, 20)
|
24.0 mL/min/1.73 m^2
Standard Deviation 33.34
|
8.6 mL/min/1.73 m^2
Standard Deviation 31.89
|
12.2 mL/min/1.73 m^2
Standard Deviation 21.59
|
-10.9 mL/min/1.73 m^2
Standard Deviation 30.53
|
-23.3 mL/min/1.73 m^2
Standard Deviation 28.74
|
|
Mean Change From Baseline in Calculated GFR During the LTE
12 months; (n=29, 25, 24, 36, 24)
|
88.1 mL/min/1.73 m^2
Standard Deviation 21.45
|
101.3 mL/min/1.73 m^2
Standard Deviation 25.01
|
94.8 mL/min/1.73 m^2
Standard Deviation 27.89
|
67.8 mL/min/1.73 m^2
Standard Deviation 22.07
|
61.7 mL/min/1.73 m^2
Standard Deviation 20.49
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 12 months; (n=26, 23, 20, 31,21)
|
22.6 mL/min/1.73 m^2
Standard Deviation 29.57
|
19.4 mL/min/1.73 m^2
Standard Deviation 30.28
|
16.5 mL/min/1.73 m^2
Standard Deviation 24.91
|
-9.3 mL/min/1.73 m^2
Standard Deviation 34.30
|
-20.2 mL/min/1.73 m^2
Standard Deviation 27.65
|
|
Mean Change From Baseline in Calculated GFR During the LTE
18 months; (n=24, 25, 21, 33, 21)
|
84.8 mL/min/1.73 m^2
Standard Deviation 24.10
|
95.0 mL/min/1.73 m^2
Standard Deviation 24.54
|
91.3 mL/min/1.73 m^2
Standard Deviation 25.35
|
69.0 mL/min/1.73 m^2
Standard Deviation 22.84
|
63.2 mL/min/1.73 m^2
Standard Deviation 21.25
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 18 months; (n=21, 23, 17, 28,18)
|
22.5 mL/min/1.73 m^2
Standard Deviation 34.16
|
11.2 mL/min/1.73 m^2
Standard Deviation 34.07
|
7.4 mL/min/1.73 m^2
Standard Deviation 20.11
|
-6.8 mL/min/1.73 m^2
Standard Deviation 31.26
|
-6.1 mL/min/1.73 m^2
Standard Deviation 22.80
|
|
Mean Change From Baseline in Calculated GFR During the LTE
24 months; (n=13, 15, 15, 22, 15)
|
84.8 mL/min/1.73 m^2
Standard Deviation 26.18
|
87.6 mL/min/1.73 m^2
Standard Deviation 21.43
|
96.3 mL/min/1.73 m^2
Standard Deviation 26.02
|
73.3 mL/min/1.73 m^2
Standard Deviation 22.82
|
66.3 mL/min/1.73 m^2
Standard Deviation 21.63
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 24 months; (n=10, 13, 11, 19,13)
|
27.9 mL/min/1.73 m^2
Standard Deviation 33.76
|
9.9 mL/min/1.73 m^2
Standard Deviation 37.62
|
15.2 mL/min/1.73 m^2
Standard Deviation 19.64
|
-2.2 mL/min/1.73 m^2
Standard Deviation 32.67
|
2.3 mL/min/1.73 m^2
Standard Deviation 24.58
|
|
Mean Change From Baseline in Calculated GFR During the LTE
At 30 months; (n=6, 6, 6, 12, 7)
|
102.9 mL/min/1.73 m^2
Standard Deviation 20.92
|
94.4 mL/min/1.73 m^2
Standard Deviation 31.78
|
90.4 mL/min/1.73 m^2
Standard Deviation 22.76
|
64.1 mL/min/1.73 m^2
Standard Deviation 27.30
|
59.5 mL/min/1.73 m^2
Standard Deviation 20.47
|
|
Mean Change From Baseline in Calculated GFR During the LTE
Change from BL to 30 months; (n=5, 5, 3, 8, 6)
|
41.4 mL/min/1.73 m^2
Standard Deviation 33.98
|
40.4 mL/min/1.73 m^2
Standard Deviation 38.10
|
17.1 mL/min/1.73 m^2
Standard Deviation 26.76
|
-15.0 mL/min/1.73 m^2
Standard Deviation 38.89
|
-10.7 mL/min/1.73 m^2
Standard Deviation 13.40
|
SECONDARY outcome
Timeframe: Baseline (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n= participants who have both baseline and postbaseline values.
Measurement of SCr is commonly used as an indicator of renal function. High creatinine blood level is an indicator of deficient filtering by the kidney. SCr was determined at baseline and various post-baseline time points.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
Change from BL to 1 months; (n=43, 38, 37, 41, 45)
|
-0.5 mg/dL
Standard Deviation 1.35
|
-0.1 mg/dL
Standard Deviation 0.50
|
-0.1 mg/dL
Standard Deviation 0.48
|
0.1 mg/dL
Standard Deviation 0.52
|
0.3 mg/dL
Standard Deviation 0.75
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
Baseline (BL); (n=47, 42, 42, 45, 45)
|
1.4 mg/dL
Standard Deviation 1.25
|
1.0 mg/dL
Standard Deviation 0.39
|
0.9 mg/dL
Standard Deviation 0.38
|
1.1 mg/dL
Standard Deviation 0.54
|
1.0 mg/dL
Standard Deviation 0.40
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
At 1 months; (n=45, 44, 42, 49, 49)
|
0.9 mg/dL
Standard Deviation 0.38
|
0.8 mg/dL
Standard Deviation 0.32
|
0.9 mg/dL
Standard Deviation 0.42
|
1.2 mg/dL
Standard Deviation 0.41
|
1.3 mg/dL
Standard Deviation 0.68
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
At 2 months; (n=29, 30, 23, 25, 27)
|
0.9 mg/dL
Standard Deviation 0.21
|
0.8 mg/dL
Standard Deviation 0.22
|
0.8 mg/dL
Standard Deviation 0.28
|
1.0 mg/dL
Standard Deviation 0.30
|
1.2 mg/dL
Standard Deviation 0.36
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
Change from BL to 2 months; (n=28, 26, 20, 22, 25)
|
-0.7 mg/dL
Standard Deviation 1.54
|
-0.2 mg/dL
Standard Deviation 0.32
|
-0.2 mg/dL
Standard Deviation 0.32
|
0.0 mg/dL
Standard Deviation 0.73
|
0.2 mg/dL
Standard Deviation 0.45
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
At 3 months; (n=36, 36, 35, 46, 37)
|
0.9 mg/dL
Standard Deviation 0.27
|
0.9 mg/dL
Standard Deviation 0.21
|
0.8 mg/dL
Standard Deviation 0.24
|
1.2 mg/dL
Standard Deviation 0.36
|
1.3 mg/dL
Standard Deviation 0.53
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
Change from BL to 3 months; (n=33, 34, 30, 40, 33)
|
-0.6 mg/dL
Standard Deviation 1.45
|
-0.1 mg/dL
Standard Deviation 0.44
|
-0.1 mg/dL
Standard Deviation 0.32
|
0.1 mg/dL
Standard Deviation 0.50
|
0.3 mg/dL
Standard Deviation 0.42
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
At 6 months; (n=39, 34, 38, 49, 36)
|
1.0 mg/dL
Standard Deviation 0.30
|
0.9 mg/dL
Standard Deviation 0.20
|
0.9 mg/dL
Standard Deviation 0.42
|
1.3 mg/dL
Standard Deviation 0.44
|
1.3 mg/dL
Standard Deviation 0.51
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
Change from BL to 6 months; (n=37, 30, 33, 42, 31)
|
-0.5 mg/dL
Standard Deviation 1.39
|
0.0 mg/dL
Standard Deviation 0.41
|
0.1 mg/dL
Standard Deviation 0.43
|
0.2 mg/dL
Standard Deviation 0.60
|
0.4 mg/dL
Standard Deviation 0.50
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
At 12 months; (n=40, 33, 35, 46, 38)
|
1.0 mg/dL
Standard Deviation 0.26
|
0.8 mg/dL
Standard Deviation 0.16
|
1.0 mg/dL
Standard Deviation 0.37
|
1.2 mg/dL
Standard Deviation 0.49
|
1.2 mg/dL
Standard Deviation 0.32
|
|
Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12
Change from BL to 12 months; (n=37, 29, 30, 41,33)
|
-0.5 mg/dL
Standard Deviation 1.38
|
-0.2 mg/dL
Standard Deviation 0.42
|
0.1 mg/dL
Standard Deviation 0.47
|
0.1 mg/dL
Standard Deviation 0.63
|
0.3 mg/dL
Standard Deviation 0.33
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 2, and 12 months posttransplantPopulation: ITT population: all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Cystatin C is a protein encoded by the CST3 gene, which is mainly used as a biomarker of kidney function. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Mean Change in Baseline Values of Cystatin C at 2 and 12 Months
Baseline (BL); (n=44, 47, 48, 49, 43)
|
1.2 mg/L
Standard Deviation 0.64
|
1.2 mg/L
Standard Deviation 0.57
|
1.1 mg/L
Standard Deviation 0.39
|
1.4 mg/L
Standard Deviation 0.73
|
1.2 mg/L
Standard Deviation 0.60
|
|
Mean Change in Baseline Values of Cystatin C at 2 and 12 Months
2 months; (n=40, 39, 39, 48, 43)
|
1.1 mg/L
Standard Deviation 0.26
|
1.1 mg/L
Standard Deviation 0.48
|
1.0 mg/L
Standard Deviation 0.25
|
1.4 mg/L
Standard Deviation 0.52
|
1.5 mg/L
Standard Deviation 0.47
|
|
Mean Change in Baseline Values of Cystatin C at 2 and 12 Months
Change from BL to 2 months; (n=35, 38, 38, 44,37)
|
-0.2 mg/L
Standard Deviation 0.62
|
-0.1 mg/L
Standard Deviation 0.72
|
-0.1 mg/L
Standard Deviation 0.31
|
0.1 mg/L
Standard Deviation 0.77
|
0.3 mg/L
Standard Deviation 0.70
|
|
Mean Change in Baseline Values of Cystatin C at 2 and 12 Months
12 months; (n=40, 36, 36, 49, 40)
|
1.1 mg/L
Standard Deviation 0.36
|
0.9 mg/L
Standard Deviation 0.28
|
1.2 mg/L
Standard Deviation 0.79
|
1.3 mg/L
Standard Deviation 0.53
|
1.3 mg/L
Standard Deviation 0.35
|
|
Mean Change in Baseline Values of Cystatin C at 2 and 12 Months
Change from BL to 12 months; (n=35, 35, 35,45,34)
|
-0.2 mg/L
Standard Deviation 0.64
|
-0.2 mg/L
Standard Deviation 0.63
|
0.1 mg/L
Standard Deviation 0.86
|
-0.1 mg/L
Standard Deviation 0.69
|
0.1 mg/L
Standard Deviation 0.63
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Maximum Plasma Concentration (Cmax) is the maximum observed serum drug concentration.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=12 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=11 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=11 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept Pharmacokinetic (PK) Parameter: Maximum Serum Concentration
|
221.3 µg/mL
Geometric Coefficient of Variation 29
|
227.6 µg/mL
Geometric Coefficient of Variation 23
|
205.4 µg/mL
Geometric Coefficient of Variation 20
|
—
|
—
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Maximum Plasma Concentration (Tmax) is the time taken to reach the maximum observed plasma concentration.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=12 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=11 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=11 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept Pharmacokinetic (PK) Parameter: Time to Achieve the Maximum Plasma Concentration
|
1.00 hour
Interval 0.5 to 1.67
|
1.08 hour
Interval 0.75 to 1.5
|
1.00 hour
Interval 0.83 to 1.17
|
—
|
—
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Area under the plasma concentration-time curve for each dosing interval is determined using the linear trapezoidal rule. The AUC(TAU) of belatacept from the MI regimens and LI regimens were calculated over 2 and 4 weeks respectively.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=10 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=5 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=6 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept PK Parameter: Area Under the Serum Concentration-time Curve to the End of the Dosing Period (AUCtau)
|
19865 µg*h/mL
Geometric Coefficient of Variation 21
|
21526 µg*h/mL
Geometric Coefficient of Variation 44
|
19730 µg*h/mL
Geometric Coefficient of Variation 22
|
—
|
—
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=13 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=11 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=12 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept PK Parameter: Minimum Plasma Concentration
|
23.63 µg/mL
Geometric Coefficient of Variation 30
|
27.20 µg/mL
Geometric Coefficient of Variation 37
|
5.91 µg/mL
Geometric Coefficient of Variation 50
|
—
|
—
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Terminal Half-life (T 1/2) is the time a drug takes for the concentration levels to fall to 50% of their value.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=10 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=5 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=7 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept PK Parameter: Terminal Half-life
|
240.80 hour
Standard Deviation 47.82
|
227.74 hour
Standard Deviation 56.15
|
207.88 hour
Standard Deviation 31.66
|
—
|
—
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism. CLT was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=10 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=5 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=6 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept PK Parameter: Total Body Clearance
|
0.45 mL/h/kg
Geometric Coefficient of Variation 28
|
0.41 mL/h/kg
Geometric Coefficient of Variation 46
|
0.45 mL/h/kg
Geometric Coefficient of Variation 22
|
—
|
—
|
SECONDARY outcome
Timeframe: Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.Population: All randomized participants who received belatacept, and had complete PK profile.
Volume of distribution (Vss) is the volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration. . Vss was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=10 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=5 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=6 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept PK Parameter: Volume of Distribution
|
0.09 L/kg
Standard Deviation 0.02
|
0.08 L/kg
Standard Deviation 0.04
|
0.11 L/kg
Standard Deviation 0.03
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 to 14Population: All randomized participants who received belatacept, and had complete PK profile.
Amount Excreted in Ascites (Ae,asc) was estimated from the ascites drug concentrations and volumes within a dosing interval.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=8 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=8 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=12 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept PK Parameter: Amount Excreted in Ascites Fluid Over Days 1 to 14
|
46654 µg
Standard Deviation 59210
|
31425 µg
Standard Deviation 40382
|
81451 µg
Standard Deviation 95931
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 to 14Population: Serum AUC was not available for the time interval corresponding to ascites fluid collection.
Clearance from ascites fluid was determined by amount excreted in ascites fluid (Ae, asc)\[0-T\] / AUC\[0-T\], where 0-T is the same duration relative to a belatacept infusion.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Samples were collected predose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105, 532, 728.Population: All randomized participants who received Belatacept, and had complete PK profile. n= participants with values at all time points.
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 168: (n=30, 29, 29)
|
7.30 µg/mL
Geometric Coefficient of Variation 58.14
|
8.01 µg/mL
Geometric Coefficient of Variation 64.97
|
3.57 µg/mL
Geometric Coefficient of Variation 52.56
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 5: (n=40, 43, 41)
|
79.15 µg/mL
Geometric Coefficient of Variation 33.32
|
79.40 µg/mL
Geometric Coefficient of Variation 33.19
|
70.88 µg/mL
Geometric Coefficient of Variation 38.66
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 14: (n=41, 43, 38)
|
32.39 µg/mL
Geometric Coefficient of Variation 40.85
|
31.16 µg/mL
Geometric Coefficient of Variation 39.74
|
29.21 µg/mL
Geometric Coefficient of Variation 47.62
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 28: (n=42, 38, 37)
|
23.51 µg/mL
Geometric Coefficient of Variation 46.71
|
22.23 µg/mL
Geometric Coefficient of Variation 47.49
|
21.72 µg/mL
Geometric Coefficient of Variation 47.64
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 56: (n=12, 13, 12)
|
18.91 µg/mL
Geometric Coefficient of Variation 39.74
|
18.84 µg/mL
Geometric Coefficient of Variation 36.85
|
6.57 µg/mL
Geometric Coefficient of Variation 82.41
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 84: (n=34, 31, 34 )
|
27.11 µg/mL
Geometric Coefficient of Variation 38.29
|
27.32 µg/mL
Geometric Coefficient of Variation 56.13
|
6.60 µg/mL
Geometric Coefficient of Variation 54.25
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 112: (n=29, 26, 29)
|
10.12 µg/mL
Geometric Coefficient of Variation 63.71
|
9.64 µg/mL
Geometric Coefficient of Variation 59.28
|
6.75 µg/mL
Geometric Coefficient of Variation 64.11
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 252: (n=28, 28, 27)
|
3.65 µg/mL
Geometric Coefficient of Variation 67.07
|
3.74 µg/mL
Geometric Coefficient of Variation 65.78
|
3.59 µg/mL
Geometric Coefficient of Variation 50.93
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 336: (n=26, 23, 21)
|
3.22 µg/mL
Geometric Coefficient of Variation 70.42
|
3.38 µg/mL
Geometric Coefficient of Variation 62.10
|
4.37 µg/mL
Geometric Coefficient of Variation 29.72
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 364: (n=28, 28, 22 )
|
2.52 µg/mL
Geometric Coefficient of Variation 70.82
|
4.01 µg/mL
Geometric Coefficient of Variation 55.68
|
3.62 µg/mL
Geometric Coefficient of Variation 48.17
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 532: (n=22, 24, 14)
|
2.71 µg/mL
Geometric Coefficient of Variation 55.53
|
4.68 µg/mL
Geometric Coefficient of Variation 57.61
|
4.91 µg/mL
Geometric Coefficient of Variation 34.49
|
—
|
—
|
|
Belatacept Trough Concentration Before Each Infusion During the LTE
Day 728: (n=10, 12, 14)
|
4.75 µg/mL
Geometric Coefficient of Variation 53.56
|
4.20 µg/mL
Geometric Coefficient of Variation 59.28
|
4.22 µg/mL
Geometric Coefficient of Variation 46.73
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score \>= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score \>= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N\>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N\>=5 in both arms, otherwise exact method was used.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=23 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=23 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=21 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=25 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=24 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months
6 months
|
39.1 percentage of participants
Interval 19.2 to 59.1
|
21.7 percentage of participants
Interval 4.9 to 38.6
|
23.8 percentage of participants
Interval 5.6 to 42.0
|
20.0 percentage of participants
Interval 4.3 to 35.7
|
33.3 percentage of participants
Interval 14.5 to 52.2
|
|
Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months
12 months
|
60.9 percentage of participants
Interval 40.9 to 80.8
|
30.4 percentage of participants
Interval 11.6 to 49.2
|
28.6 percentage of participants
Interval 9.2 to 47.9
|
52.0 percentage of participants
Interval 32.4 to 71.6
|
37.5 percentage of participants
Interval 18.1 to 56.9
|
SECONDARY outcome
Timeframe: 12 months posttransplant, end of study (database lock, 20-June-2011)Population: ITT-LTE population, all randomized and transplanted participants who entered long-term extension.
HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score \>= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score \>= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N\>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N\>=5 in both arms, otherwise exact method was used.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=12 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=12 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=9 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=17 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=11 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE
At 12 months
|
50.0 percentage of participants
Interval 21.7 to 78.3
|
41.7 percentage of participants
Interval 13.8 to 69.6
|
0 percentage of participants
Not applicable as no subjects had HCV recurrence
|
58.8 percentage of participants
Interval 35.4 to 82.2
|
72.7 percentage of participants
Interval 46.4 to 99.0
|
|
Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE
At end of study
|
66.7 percentage of participants
Interval 40.0 to 93.3
|
50.0 percentage of participants
Interval 21.7 to 78.3
|
22.2 percentage of participants
Interval 2.8 to 60.0
|
64.7 percentage of participants
Interval 42.0 to 87.4
|
72.7 percentage of participants
Interval 46.4 to 99.0
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 6 and 12 months (mo) posttransplantPopulation: ITT population, all randomized and transplanted participants. n= participants who were HCV positive at baseline.
Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels \> 2.4 \* 10\^6 U/mL and \> 4.7 \* 10\^6 U/mL were descriptively summarized by treatment group. BL=baseline
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=23 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=23 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=21 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=25 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=24 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase
BL; HCV RNA > 2.4*10^6 U/mL (n=21,22,19,22,23)
|
2 participants
|
4 participants
|
2 participants
|
3 participants
|
1 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase
BL; HCV RNA > 4.7 *10^6 U/mL (n=21,22,19,22,23)
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase
6 mo; HCV RNA > 2.4*10^6 U/mL (n=16,15,15,21,14)
|
9 participants
|
7 participants
|
8 participants
|
14 participants
|
11 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase
6 mo; HCV RNA > 4.7*10^6 U/mL (n=16,15,15,21,14)
|
7 participants
|
7 participants
|
7 participants
|
11 participants
|
10 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase
12 mo; HCV RNA > 2.4*10^6 U/mL (n=15,13,14,20,13)
|
7 participants
|
7 participants
|
7 participants
|
13 participants
|
7 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase
12 mo; HCV RNA > 4.7*10^6 U/mL (n=15,13,14,20,13)
|
6 participants
|
6 participants
|
5 participants
|
11 participants
|
7 participants
|
SECONDARY outcome
Timeframe: BL (pretransplant), 12, 18, 24, 30 months (mo) posttransplantPopulation: ITT-LTE population, all randomized and transplanted participants. n= participants with HCV RNA values.
Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels \> 2.4 x 10\^6 U/mL and \> 4.7 x 10\^6 U/mL were descriptively summarized by treatment group. BL = baseline
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=12 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=12 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=9 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=17 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=11 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
BL; HCV RNA > 2.4*10^6 U/mL (n=10,11,6,15,10)
|
0 participants
|
1 participants
|
0 participants
|
2 participants
|
1 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
12 mo; HCV RNA > 2.4*10^6 U/mL (n=11,10,8,16,10)
|
6 participants
|
5 participants
|
4 participants
|
10 participants
|
4 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
12 mo; HCV RNA > 4.7*10^6 U/mL (n=11,10,8,16,10)
|
6 participants
|
4 participants
|
3 participants
|
8 participants
|
4 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
18 mo; HCV RNA > 2.4*10^6 U/mL (n=7,10,3,12,9)
|
3 participants
|
2 participants
|
2 participants
|
7 participants
|
3 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
18 mo; HCV RNA > 4.7*10^6 U/mL (n=7,10,3,12,9)
|
2 participants
|
2 participants
|
2 participants
|
6 participants
|
2 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
24 mo; HCV RNA > 2.4*10^6 U/mL (n=4,3,4,8,4)
|
2 participants
|
1 participants
|
1 participants
|
6 participants
|
1 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
24 mo; HCV RNA > 4.7*10^6 U/mL (n=4,3,4,8,4)
|
2 participants
|
0 participants
|
0 participants
|
5 participants
|
1 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
30 mo; HCV RNA > 2.4*10^6 U/mL (n=1,1,1,2,2)
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE
30 mo; HCV RNA > 4.7*10^6 U/mL (n=1,1,1,2,2)
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants who did not have dyslipidemia at baseline
Percentage of participants who develop dyslipidemia, defined as hypertriglyceridemia (triglycerides \[TGs\] ≥ 500 mg/dL \[5.65 mmol/L\]), hypercholesterolemia (Low density lipoprotein \[LDL\] ≥ 100 mg/dL \[2.59 mmol/L\]), or elevated non-high density lipoprotein (non- high density lipoprotein \[HDL\] ≥ 130 mg/dL \[3.36 mmol/L\]) in the presence of high TGs (TGs ≥ 200 mg/dL \[2.26 mmol/L\]).
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=42 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=35 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=46 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=42 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=37 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase
By 6 month: Dyslipidemia
|
50.0 percentage of participants
Interval 34.9 to 65.1
|
54.3 percentage of participants
Interval 37.8 to 70.8
|
45.7 percentage of participants
Interval 31.3 to 60.0
|
33.3 percentage of participants
Interval 19.1 to 47.6
|
59.5 percentage of participants
Interval 43.6 to 75.3
|
|
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase
By 6 month: Hypertriglyceridemia
|
2.4 percentage of participants
Interval 0.1 to 12.6
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase
By 6 month: Hypercholesterolemia
|
42.9 percentage of participants
Interval 27.9 to 57.8
|
48.6 percentage of participants
Interval 32.0 to 65.1
|
39.1 percentage of participants
Interval 25.0 to 53.2
|
28.6 percentage of participants
Interval 14.9 to 42.2
|
51.4 percentage of participants
Interval 35.2 to 67.5
|
|
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase
By 12 month: Dyslipidemia
|
59.5 percentage of participants
Interval 44.7 to 74.4
|
57.1 percentage of participants
Interval 40.7 to 73.5
|
58.7 percentage of participants
Interval 44.5 to 72.9
|
50.0 percentage of participants
Interval 34.9 to 65.1
|
70.3 percentage of participants
Interval 55.5 to 85.0
|
|
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase
By 12 month: Hypertriglyceridemia
|
4.8 percentage of participants
Interval 0.6 to 16.2
|
0 percentage of participants
Interval 0.0 to 0.0
|
2.2 percentage of participants
Interval 0.1 to 11.5
|
2.4 percentage of participants
Interval 0.1 to 12.6
|
0 percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase
By 12 month: Hypercholesterolemia
|
54.8 percentage of participants
Interval 39.7 to 69.8
|
54.3 percentage of participants
Interval 37.8 to 70.8
|
52.2 percentage of participants
Interval 37.7 to 66.6
|
42.9 percentage of participants
Interval 27.9 to 57.8
|
62.2 percentage of participants
Interval 46.5 to 77.8
|
SECONDARY outcome
Timeframe: 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
Percentage of participants at any given time (at Month 6 and Month 12) who met the definition of dyslipidemia.Dyslipidemia is defined as hypertriglyceridemia (TGs ≥ 500 mg/dL \[5.65 mmol/L\]), hypercholesterolemia (LDL ≥ 100 mg/dL \[2.59 mmol/L\]), or elevated non-HDL (non-HDL ≥ 130 mg/dL \[3.36 mmol/L\]) in the presence of high TGs (TGs ≥ 200 mg/dL \[2.26 mmol/L\]).
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase
6 months: Dyslipidemia
|
36.0 percentage of participants
Interval 22.7 to 49.3
|
31.3 percentage of participants
Interval 18.1 to 44.4
|
30.6 percentage of participants
Interval 17.7 to 43.5
|
32.1 percentage of participants
Interval 19.5 to 44.6
|
26.0 percentage of participants
Interval 13.8 to 38.2
|
|
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase
6 months: Hypertriglyceridemia
|
6.0 percentage of participants
Interval 1.3 to 16.5
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase
6 months: Hypercholesterolemia
|
30.0 percentage of participants
Interval 17.3 to 42.7
|
29.2 percentage of participants
Interval 16.3 to 42.0
|
24.5 percentage of participants
Interval 12.4 to 36.5
|
30.2 percentage of participants
Interval 17.8 to 42.5
|
22.0 percentage of participants
Interval 10.5 to 33.5
|
|
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase
12 months: Dyslipidemia
|
40.0 percentage of participants
Interval 26.4 to 53.6
|
33.3 percentage of participants
Interval 20.0 to 46.7
|
44.9 percentage of participants
Interval 31.0 to 58.8
|
34.0 percentage of participants
Interval 21.2 to 46.7
|
42.0 percentage of participants
Interval 28.3 to 55.7
|
|
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase
12 months: Hypertriglyceridemia
|
4.0 percentage of participants
Interval 0.5 to 13.7
|
0 percentage of participants
Interval 0.0 to 0.0
|
2.0 percentage of participants
Interval 0.1 to 10.9
|
1.9 percentage of participants
Interval 0.0 to 10.1
|
2.0 percentage of participants
Interval 0.1 to 10.6
|
|
Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase
12 months: Hypercholesterolemia
|
30.0 percentage of participants
Interval 17.3 to 42.7
|
29.2 percentage of participants
Interval 16.3 to 42.0
|
40.8 percentage of participants
Interval 27.1 to 54.6
|
30.2 percentage of participants
Interval 17.8 to 42.5
|
36.0 percentage of participants
Interval 22.7 to 49.3
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 1, 6, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
BL (n=45, 42, 44, 49, 46)
|
80.4 mg/dL
Standard Deviation 37.1
|
83.5 mg/dL
Standard Deviation 44.2
|
84.8 mg/dL
Standard Deviation 60.76
|
77.7 mg/dL
Standard Deviation 44.30
|
76.8 mg/dL
Standard Deviation 46.85
|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
1 months (n=46, 47, 42, 49, 49)
|
125.1 mg/dL
Standard Deviation 42.91
|
147.9 mg/dL
Standard Deviation 82.96
|
148.0 mg/dL
Standard Deviation 71.11
|
121.7 mg/dL
Standard Deviation 40.25
|
130.0 mg/dL
Standard Deviation 50.75
|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
Change from BL to 1 months (n=42, 41, 39, 45, 45)
|
47.2 mg/dL
Standard Deviation 50.14
|
66.0 mg/dL
Standard Deviation 102.0
|
54.1 mg/dL
Standard Deviation 86.63
|
47.0 mg/dL
Standard Deviation 61.36
|
47.5 mg/dL
Standard Deviation 50.32
|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
6 months (n=39, 34, 38, 48, 36)
|
139.3 mg/dL
Standard Deviation 48.93
|
134.4 mg/dL
Standard Deviation 45.16
|
138.9 mg/dL
Standard Deviation 43.39
|
125.1 mg/dL
Standard Deviation 44.02
|
135.4 mg/dL
Standard Deviation 58.49
|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
Change from BL to 6 months (n=35, 30, 35, 44, 32)
|
59.5 mg/dL
Standard Deviation 48.06
|
44.0 mg/dL
Standard Deviation 54.37
|
48.2 mg/dL
Standard Deviation 75.74
|
48.1 mg/dL
Standard Deviation 51.09
|
48.6 mg/dL
Standard Deviation 76.78
|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
12 months (n=40, 33, 35, 45, 37)
|
143.2 mg/dL
Standard Deviation 84.77
|
137.4 mg/dL
Standard Deviation 38.49
|
142.2 mg/dL
Standard Deviation 62.41
|
118.2 mg/dL
Standard Deviation 43.00
|
131.9 mg/dL
Standard Deviation 39.71
|
|
Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase
Change from BL to 12 months (n=35, 29, 32, 42, 33)
|
66.7 mg/dL
Standard Deviation 80.64
|
49.2 mg/dL
Standard Deviation 63.87
|
53.4 mg/dL
Standard Deviation 97.28
|
47.4 mg/dL
Standard Deviation 54.80
|
44.1 mg/dL
Standard Deviation 72.35
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 1, 6, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
BL (n=46, 42, 44, 49, 46)
|
32.1 mg/dL
Standard Deviation 17.38
|
36.2 mg/dL
Standard Deviation 17.49
|
36.5 mg/dL
Standard Deviation 19.66
|
33.3 mg/dL
Standard Deviation 21.97
|
31.1 mg/dL
Standard Deviation 15.50
|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
1 month (n=46, 47, 42, 49, 49)
|
41.3 mg/dL
Standard Deviation 15.37
|
36.9 mg/dL
Standard Deviation 17.80
|
42.5 mg/dL
Standard Deviation 19.60
|
41.2 mg/dL
Standard Deviation 11.32
|
34.1 mg/dL
Standard Deviation 14.11
|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
Change from BL to 1month (n=43, 41, 39, 45, 45)
|
9.9 mg/dL
Standard Deviation 26.83
|
1.7 mg/dL
Standard Deviation 26.15
|
7.2 mg/dL
Standard Deviation 27.72
|
7.1 mg/dL
Standard Deviation 22.65
|
3.4 mg/dL
Standard Deviation 21.37
|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
6 months (n=39, 34, 38, 48, 36)
|
41.5 mg/dL
Standard Deviation 14.29
|
42.8 mg/dL
Standard Deviation 14.17
|
44.2 mg/dL
Standard Deviation 14.56
|
45.5 mg/dL
Standard Deviation 15.80
|
42.6 mg/dL
Standard Deviation 17.92
|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
Change from BL to 6 months (n=36, 30, 35, 44, 32)
|
9.2 mg/dL
Standard Deviation 21.56
|
7.3 mg/dL
Standard Deviation 20.40
|
9.4 mg/dL
Standard Deviation 22.06
|
10.8 mg/dL
Standard Deviation 28.26
|
9.5 mg/dL
Standard Deviation 24.32
|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
12 months (n=40, 33, 35, 45, 37)
|
43.6 mg/dL
Standard Deviation 14.40
|
41.5 mg/dL
Standard Deviation 15.19
|
44.2 mg/dL
Standard Deviation 14.37
|
45.6 mg/dL
Standard Deviation 15.35
|
43.3 mg/dL
Standard Deviation 15.58
|
|
Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase
Change from BL to12 months (n=36, 29, 32, 42, 33)
|
12.7 mg/dL
Standard Deviation 23.25
|
8.3 mg/dL
Standard Deviation 22.75
|
7.3 mg/dL
Standard Deviation 24.71
|
10.9 mg/dL
Standard Deviation 24.13
|
10.0 mg/dL
Standard Deviation 21.01
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 1, 6, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
BL (n=29, 30, 25, 34, 32)
|
52.3 mg/dL
Standard Deviation 25.26
|
58.6 mg/dL
Standard Deviation 34.97
|
58.9 mg/dL
Standard Deviation 34.08
|
63.6 mg/dL
Standard Deviation 45.02
|
59.9 mg/dL
Standard Deviation 42.60
|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
1 month (n=30, 34, 29, 41, 42)
|
95.2 mg/dL
Standard Deviation 33.82
|
93.2 mg/dL
Standard Deviation 33.73
|
115.7 mg/dL
Standard Deviation 58.88
|
89.8 mg/dL
Standard Deviation 37.31
|
98.4 mg/dL
Standard Deviation 47.68
|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
Change from BL to 1 month (n=17, 21, 17, 27, 30)
|
42.7 mg/dL
Standard Deviation 47.94
|
34.3 mg/dL
Standard Deviation 48.98
|
57.1 mg/dL
Standard Deviation 30.19
|
26.1 mg/dL
Standard Deviation 48.40
|
41.5 mg/dL
Standard Deviation 43.68
|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
6 months (n=27, 29, 27, 41, 30)
|
99.2 mg/dL
Standard Deviation 36.93
|
107.5 mg/dL
Standard Deviation 36.93
|
98.2 mg/dL
Standard Deviation 42.85
|
96.7 mg/dL
Standard Deviation 42.22
|
92.8 mg/dL
Standard Deviation 29.03
|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
Change from BL to 6 months (n=16, 19, 18, 28, 22)
|
41.2 mg/dL
Standard Deviation 33.82
|
45.9 mg/dL
Standard Deviation 42.13
|
48.7 mg/dL
Standard Deviation 41.66
|
28.9 mg/dL
Standard Deviation 49.29
|
26.1 mg/dL
Standard Deviation 54.04
|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
12 months (n=38, 29, 32, 42, 35)
|
93.0 mg/dL
Standard Deviation 30.72
|
107.2 mg/dL
Standard Deviation 32.75
|
103.2 mg/dL
Standard Deviation 36.41
|
89.0 mg/dL
Standard Deviation 37.15
|
93.8 mg/dL
Standard Deviation 27.45
|
|
Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase
Change from BL to 12 months (n=22, 19, 20, 25, 22)
|
37.8 mg/dL
Standard Deviation 33.09
|
45.4 mg/dL
Standard Deviation 51.75
|
37.2 mg/dL
Standard Deviation 47.81
|
23.7 mg/dL
Standard Deviation 46.80
|
13.7 mg/dL
Standard Deviation 50.98
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 1, 6, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
BL (n=45, 42, 44, 49, 47)
|
112.9 mg/dL
Standard Deviation 49.76
|
119.7 mg/dL
Standard Deviation 51.81
|
121.3 mg/dL
Standard Deviation 63.05
|
111.0 mg/dL
Standard Deviation 54.91
|
106.4 mg/dL
Standard Deviation 51.82
|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
1 month (n=46, 47, 42, 49, 49)
|
166.3 mg/dL
Standard Deviation 45.92
|
184.9 mg/dL
Standard Deviation 77.16
|
190.6 mg/dL
Standard Deviation 69.54
|
162.9 mg/dL
Standard Deviation 43.72
|
164.1 mg/dL
Standard Deviation 52.95
|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
Change from BL to 1 month (n=42, 41, 39, 45, 46)
|
57.0 mg/dL
Standard Deviation 63.06
|
67.7 mg/dL
Standard Deviation 102.3
|
61.3 mg/dL
Standard Deviation 84.20
|
54.0 mg/dL
Standard Deviation 70.01
|
53.4 mg/dL
Standard Deviation 57.19
|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
6 months (n=39, 34, 38, 48, 36)
|
180.8 mg/dL
Standard Deviation 52.76
|
177.3 mg/dL
Standard Deviation 49.56
|
182.2 mg/dL
Standard Deviation 45.58
|
170.6 mg/dL
Standard Deviation 49.30
|
177.9 mg/dL
Standard Deviation 57.92
|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
Change from BL to 6 months (n=35, 30, 35, 44, 33)
|
68.6 mg/dL
Standard Deviation 60.07
|
51.3 mg/dL
Standard Deviation 63.22
|
56.6 mg/dL
Standard Deviation 72.89
|
58.9 mg/dL
Standard Deviation 66.3
|
60.8 mg/dL
Standard Deviation 71.33
|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
12 months (n=40, 33, 35, 45, 37)
|
186.8 mg/dL
Standard Deviation 87.16
|
178.9 mg/dL
Standard Deviation 42.13
|
186.4 mg/dL
Standard Deviation 59.11
|
163.8 mg/dL
Standard Deviation 46.41
|
175.2 mg/dL
Standard Deviation 38.37
|
|
Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase
Change from BL to 12 months (n=35, 29,32, 42, 34)
|
79.4 mg/dL
Standard Deviation 86.88
|
57.5 mg/dL
Standard Deviation 73.67
|
60.7 mg/dL
Standard Deviation 92.87
|
58.2 mg/dL
Standard Deviation 64.05
|
57.3 mg/dL
Standard Deviation 72.22
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 1, 6, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
BL (n=29, 30, 25, 34, 32)
|
94.4 mg/dL
Standard Deviation 60.42
|
110.1 mg/dL
Standard Deviation 135.1
|
80.2 mg/dL
Standard Deviation 46.29
|
84.4 mg/dL
Standard Deviation 34.22
|
89.2 mg/dL
Standard Deviation 73.45
|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
1 month (n=29, 33, 29, 41, 43)
|
153.9 mg/dL
Standard Deviation 65.83
|
162.9 mg/dL
Standard Deviation 108.1
|
149.0 mg/dL
Standard Deviation 72.84
|
149.1 mg/dL
Standard Deviation 61.27
|
163.5 mg/dL
Standard Deviation 73.80
|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
Change from BL to 1 month (n=16, 20, 17, 27, 30)
|
71.2 mg/dL
Standard Deviation 84.87
|
45.7 mg/dL
Standard Deviation 223.0
|
85.8 mg/dL
Standard Deviation 93.63
|
68.2 mg/dL
Standard Deviation 75.45
|
71.8 mg/dL
Standard Deviation 58.66
|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
6 months (n=26, 29, 25, 41, 30)
|
234.3 mg/dL
Standard Deviation 316.6
|
157.1 mg/dL
Standard Deviation 82.23
|
162.7 mg/dL
Standard Deviation 109.2
|
148.1 mg/dL
Standard Deviation 67.50
|
167.2 mg/dL
Standard Deviation 100.8
|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
Change from BL to 6 months (n=15, 19, 18, 28, 22)
|
199.9 mg/dL
Standard Deviation 329.1
|
18.3 mg/dL
Standard Deviation 140.8
|
88.7 mg/dL
Standard Deviation 113.1
|
60.8 mg/dL
Standard Deviation 63.06
|
84.3 mg/dL
Standard Deviation 105.2
|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
12 months (n=38, 29, 32, 42, 34)
|
255.1 mg/dL
Standard Deviation 582.7
|
159.0 mg/dL
Standard Deviation 70.77
|
158.2 mg/dL
Standard Deviation 99.93
|
156.4 mg/dL
Standard Deviation 105.7
|
190.5 mg/dL
Standard Deviation 125.7
|
|
Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase
Change from BL to 12 months (n=22, 19, 20, 25, 21)
|
237.2 mg/dL
Standard Deviation 703.9
|
20.3 mg/dL
Standard Deviation 180.9
|
91.6 mg/dL
Standard Deviation 118.0
|
72.3 mg/dL
Standard Deviation 60.61
|
92.6 mg/dL
Standard Deviation 116.4
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 1, 3, 6, 9, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
BL (n=50, 48, 49, 53, 49)
|
115.3 mm Hg
Standard Deviation 18.41
|
115.4 mm Hg
Standard Deviation 22.35
|
111.4 mm Hg
Standard Deviation 15.80
|
121.2 mm Hg
Standard Deviation 17.31
|
125.3 mm Hg
Standard Deviation 21.87
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
1 month (n=50, 48, 49, 52, 48)
|
123.3 mm Hg
Standard Deviation 16.87
|
126.3 mm Hg
Standard Deviation 15.44
|
120.9 mm Hg
Standard Deviation 16.96
|
129.2 mm Hg
Standard Deviation 13.79
|
124.6 mm Hg
Standard Deviation 16.41
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
Change from BL to 1 month (n=50, 48, 49, 52, 47)
|
8.0 mm Hg
Standard Deviation 19.95
|
10.9 mm Hg
Standard Deviation 27.03
|
9.4 mm Hg
Standard Deviation 21.65
|
8.5 mm Hg
Standard Deviation 18.43
|
0.6 mm Hg
Standard Deviation 24.26
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
3 months (n=44, 46, 41, 48, 42)
|
127.0 mm Hg
Standard Deviation 15.04
|
126.9 mm Hg
Standard Deviation 15.03
|
124.4 mm Hg
Standard Deviation 17.65
|
136.9 mm Hg
Standard Deviation 18.61
|
133.0 mm Hg
Standard Deviation 16.18
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
Change from BL to 3 months (n=44, 46, 41, 48, 41)
|
10.9 mm Hg
Standard Deviation 23.10
|
11.7 mm Hg
Standard Deviation 23.85
|
12.7 mm Hg
Standard Deviation 21.30
|
16.3 mm Hg
Standard Deviation 24.64
|
9.1 mm Hg
Standard Deviation 24.99
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
6 months (n=43, 40, 36, 47, 37)
|
124.0 mm Hg
Standard Deviation 16.09
|
126.5 mm Hg
Standard Deviation 15.87
|
124.6 mm Hg
Standard Deviation 14.75
|
130.6 mm Hg
Standard Deviation 23.29
|
132.0 mm Hg
Standard Deviation 22.11
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
Change from BL to 6 months (n=43, 40, 36, 47, 36)
|
8.4 mm Hg
Standard Deviation 23.18
|
9.3 mm Hg
Standard Deviation 24.44
|
12.8 mm Hg
Standard Deviation 19.77
|
10.0 mm Hg
Standard Deviation 26.62
|
8.3 mm Hg
Standard Deviation 27.45
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
9 months (n=34, 30, 29, 41, 31)
|
125.5 mm Hg
Standard Deviation 16.24
|
125.8 mm Hg
Standard Deviation 13.16
|
123.9 mm Hg
Standard Deviation 12.22
|
135.6 mm Hg
Standard Deviation 20.81
|
133.9 mm Hg
Standard Deviation 15.58
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
Change from BL to 9 months (n=34, 30, 29, 41, 31)
|
10.4 mm Hg
Standard Deviation 21.36
|
8.8 mm Hg
Standard Deviation 29.71
|
13.3 mm Hg
Standard Deviation 21.94
|
14.4 mm Hg
Standard Deviation 26.73
|
11.6 mm Hg
Standard Deviation 20.39
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
12 months (n=42, 37, 36, 46, 38)
|
125.8 mm Hg
Standard Deviation 12.79
|
127.0 mm Hg
Standard Deviation 17.02
|
121.2 mm Hg
Standard Deviation 13.06
|
137.0 mm Hg
Standard Deviation 18.09
|
138.0 mm Hg
Standard Deviation 18.67
|
|
Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase
Change from BL to 12 months (n=42, 37, 36, 46, 37)
|
9.2 mm Hg
Standard Deviation 22.96
|
10.2 mm Hg
Standard Deviation 27.33
|
10.6 mm Hg
Standard Deviation 17.46
|
15.9 mm Hg
Standard Deviation 25.60
|
14.6 mm Hg
Standard Deviation 25.88
|
SECONDARY outcome
Timeframe: BL (pretransplant), 1, 3, 6, 9, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Participants were considered to have hypertension if they had Diastolic Blood Pressure (SBP) ≥ 80 mmHg.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
Change from BL to 12 months (n=42, 37, 36, 46, 37)
|
10.26 mm Hg
Standard Deviation 15.71
|
16.3 mm Hg
Standard Deviation 15.28
|
10.6 mm Hg
Standard Deviation 14.35
|
10.21 mm Hg
Standard Deviation 13.6
|
10.8 mm Hg
Standard Deviation 13.20
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
BL (n=50, 48, 49, 53, 49)
|
64.5 mm Hg
Standard Deviation 12.86
|
63.1 mm Hg
Standard Deviation 11.50
|
62.9 mm Hg
Standard Deviation 10.54
|
67.5 mm Hg
Standard Deviation 12.55
|
68.6 mm Hg
Standard Deviation 12.07
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
1 month (n=50, 48, 49, 52, 48)
|
74.4 mm Hg
Standard Deviation 10.34
|
74.7 mm Hg
Standard Deviation 9.51
|
72.6 mm Hg
Standard Deviation 13.84
|
77.8 mm Hg
Standard Deviation 10.26
|
74.6 mm Hg
Standard Deviation 10.76
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
Change from BL to 1 month (n=50, 48, 49, 52, 47)
|
10.0 mm Hg
Standard Deviation 14.53
|
11.7 mm Hg
Standard Deviation 12.48
|
9.7 mm Hg
Standard Deviation 16.27
|
10.7 mm Hg
Standard Deviation 13.80
|
5.8 mm Hg
Standard Deviation 14.05
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
3 months (n=44, 46, 41, 48, 42)
|
77.4 mm Hg
Standard Deviation 9.57
|
78.3 mm Hg
Standard Deviation 10.85
|
76.1 mm Hg
Standard Deviation 10.81
|
81.7 mm Hg
Standard Deviation 10.94
|
78.2 mm Hg
Standard Deviation 9.86
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
Change from BL to 3 months (n=44, 46, 41, 48, 41)
|
11.5 mm Hg
Standard Deviation 14.32
|
15.2 mm Hg
Standard Deviation 11.90
|
12.0 mm Hg
Standard Deviation 15.70
|
14.4 mm Hg
Standard Deviation 15.27
|
9.9 mm Hg
Standard Deviation 15.35
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
6 months (n=43, 40, 36, 47, 37)
|
74.4 mm Hg
Standard Deviation 10.63
|
79.4 mm Hg
Standard Deviation 10.17
|
76.3 mm Hg
Standard Deviation 9.69
|
77.8 mm Hg
Standard Deviation 12.68
|
76.6 mm Hg
Standard Deviation 9.11
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
Change from BL to 6 months (n=43, 40, 36, 47, 36)
|
8.8 mm Hg
Standard Deviation 15.49
|
17.0 mm Hg
Standard Deviation 12.86
|
12.5 mm Hg
Standard Deviation 14.93
|
10.7 mm Hg
Standard Deviation 14.44
|
8.6 mm Hg
Standard Deviation 14.58
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
9 months (n=34, 30, 29, 41, 31)
|
75.4 mm Hg
Standard Deviation 9.96
|
78.5 mm Hg
Standard Deviation 11.45
|
77.6 mm Hg
Standard Deviation 9.10
|
79.5 mm Hg
Standard Deviation 10.74
|
79.5 mm Hg
Standard Deviation 10.15
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
Change from BL to 9 months (n=34, 30, 29, 41, 31)
|
10.0 mm Hg
Standard Deviation 14.41
|
15.2 mm Hg
Standard Deviation 16.91
|
13.2 mm Hg
Standard Deviation 14.54
|
11.2 mm Hg
Standard Deviation 15.37
|
11.2 mm Hg
Standard Deviation 13.25
|
|
Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase
12 months (n=42, 37, 36, 46, 38)
|
76.5 mm Hg
Standard Deviation 9.38
|
78.5 mm Hg
Standard Deviation 11.43
|
74.5 mm Hg
Standard Deviation 8.54
|
80.3 mm Hg
Standard Deviation 10.21
|
79.5 mm Hg
Standard Deviation 11.24
|
SECONDARY outcome
Timeframe: BL (pretransplant), 1, 3, 6, 9, 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
Change from BL to 12 months (n=42, 37, 36, 46, 37)
|
10.1 mm Hg
Standard Deviation 15.41
|
14.3 mm Hg
Standard Deviation 18.11
|
10.6 mm Hg
Standard Deviation 13.06
|
14.3 mm Hg
Standard Deviation 17.12
|
12.1 mm Hg
Standard Deviation 15.76
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
BL (n=50, 48, 49, 53, 49)
|
81.4 mm Hg
Standard Deviation 12.98
|
80.5 mm Hg
Standard Deviation 13.58
|
79.1 mm Hg
Standard Deviation 10.32
|
85.4 mm Hg
Standard Deviation 12.97
|
87.5 mm Hg
Standard Deviation 13.42
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
1 month (n=50, 48, 49, 52, 48)
|
90.7 mm Hg
Standard Deviation 10.97
|
91.9 mm Hg
Standard Deviation 10.44
|
88.7 mm Hg
Standard Deviation 14.09
|
95.0 mm Hg
Standard Deviation 9.89
|
91.3 mm Hg
Standard Deviation 11.61
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
Change from BL to 1 month (n=50, 48, 49, 52, 47)
|
9.3 mm Hg
Standard Deviation 14.58
|
11.4 mm Hg
Standard Deviation 14.96
|
9.6 mm Hg
Standard Deviation 16.75
|
10.0 mm Hg
Standard Deviation 13.86
|
4.1 mm Hg
Standard Deviation 15.76
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
3 months (n=44, 46, 41, 48, 41)
|
93.9 mm Hg
Standard Deviation 9.78
|
94.5 mm Hg
Standard Deviation 11.14
|
92.2 mm Hg
Standard Deviation 12.18
|
100.1 mm Hg
Standard Deviation 12.29
|
96.5 mm Hg
Standard Deviation 9.01
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
Change from BL to 3 months (n=44, 46, 41, 48, 41)
|
11.3 mm Hg
Standard Deviation 15.40
|
14.0 mm Hg
Standard Deviation 14.21
|
12.2 mm Hg
Standard Deviation 15.95
|
15.1 mm Hg
Standard Deviation 17.11
|
9.6 mm Hg
Standard Deviation 15.59
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
6 months (n=43, 40, 36, 47, 37)
|
91.0 mm Hg
Standard Deviation 10.70
|
95.1 mm Hg
Standard Deviation 10.92
|
92.4 mm Hg
Standard Deviation 9.94
|
95.4 mm Hg
Standard Deviation 15.04
|
95.0 mm Hg
Standard Deviation 11.70
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
Change from BL to 6 months (n=43, 40, 36, 47, 36)
|
8.7 mm Hg
Standard Deviation 15.71
|
14.4 mm Hg
Standard Deviation 15.63
|
12.6 mm Hg
Standard Deviation 14.35
|
10.5 mm Hg
Standard Deviation 17.18
|
8.5 mm Hg
Standard Deviation 16.74
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
9 months (n=34, 30, 29, 41, 31)
|
92.1 mm Hg
Standard Deviation 10.41
|
94.3 mm Hg
Standard Deviation 10.22
|
93.0 mm Hg
Standard Deviation 8.68
|
98.2 mm Hg
Standard Deviation 12.46
|
97.7 mm Hg
Standard Deviation 10.34
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
Change from BL to 9 months (n=34, 30, 29, 41, 31)
|
10.1 mm Hg
Standard Deviation 15.06
|
13.1 mm Hg
Standard Deviation 19.90
|
13.2 mm Hg
Standard Deviation 13.82
|
12.3 mm Hg
Standard Deviation 17.71
|
11.3 mm Hg
Standard Deviation 13.25
|
|
Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase
12 months (n=42, 37, 36, 46, 38)
|
93.0 mm Hg
Standard Deviation 8.61
|
94.6 mm Hg
Standard Deviation 11.90
|
90.1 mm Hg
Standard Deviation 8.89
|
99.2 mm Hg
Standard Deviation 11.56
|
99.0 mm Hg
Standard Deviation 12.13
|
SECONDARY outcome
Timeframe: 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
Percentage of participants who develop hypertension after randomization and transplantation. Transient post-operative increases in BP were not to be counted as new onset hypertension. Hypertension was to be assessed only at or after the Week 4 visit. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=17 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=15 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=16 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=16 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=12 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase
By 6 months
|
94.1 percentage of participants
Interval 82.9 to 100.0
|
93.3 percentage of participants
Interval 80.7 to 100.0
|
93.8 percentage of participants
Interval 81.9 to 100.0
|
100.0 percentage of participants
All the respondents had hypertension, hence CI was not evaluable.
|
100 percentage of participants
All the respondents had hypertension, hence CI was not evaluable.
|
|
Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase
By 12 months
|
100 percentage of participants
All the respondents had hypertension, hence confidence interval (CI) not available.
|
93.3 percentage of participants
Interval 80.7 to 100.0
|
93.8 percentage of participants
Interval 81.9 to 100.0
|
100.0 percentage of participants
All the respondents had hypertension, hence CI not evaluable.
|
100.0 percentage of participants
All the respondents had hypertension, hence CI not evaluable.
|
SECONDARY outcome
Timeframe: 6 and 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
Percentage of participants at any given time who meet the definition of hypertension. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase
By 6 months
|
64.0 percentage of participants
Interval 50.7 to 77.3
|
77.1 percentage of participants
Interval 65.2 to 89.0
|
69.4 percentage of participants
Interval 56.5 to 82.3
|
71.7 percentage of participants
Interval 59.6 to 83.8
|
70.0 percentage of participants
Interval 57.3 to 82.7
|
|
Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase
By 12 months
|
72.0 percentage of participants
Interval 59.6 to 84.4
|
68.8 percentage of participants
Interval 55.6 to 81.9
|
59.2 percentage of participants
Interval 45.4 to 72.9
|
79.2 percentage of participants
Interval 68.3 to 90.2
|
70.0 percentage of participants
Interval 57.3 to 82.7
|
SECONDARY outcome
Timeframe: 12 months posttransplantPopulation: ITT population, all randomized and transplanted participants.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=41 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=39 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=36 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=48 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=42 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Who Received Anti-hypertensive Therapy at Month 12
Received at least 1 medication
|
20 participants
|
19 participants
|
14 participants
|
26 participants
|
21 participants
|
|
Number of Participants Who Received Anti-hypertensive Therapy at Month 12
Received 1 medication
|
13 participants
|
16 participants
|
8 participants
|
17 participants
|
12 participants
|
|
Number of Participants Who Received Anti-hypertensive Therapy at Month 12
Received 3 medications
|
1 participants
|
1 participants
|
4 participants
|
3 participants
|
3 participants
|
|
Number of Participants Who Received Anti-hypertensive Therapy at Month 12
Received 4 medications
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants Who Received Anti-hypertensive Therapy at Month 12
Received 2 medications
|
6 participants
|
2 participants
|
2 participants
|
5 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 6 and 12 months posttransplantPopulation: ITT population, all randomized participants without Diabetes Mellitus (pre-transplantation).
A participant who did not have diabetes prior to randomization was determined to have NODM if(i) the participant received an antidiabetic medication for a duration of at least 30 days or(ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is\>=126 mg/dL (7.0 mmol/L). For 95% CI within each group, normal approximation is used if N\>=5. For 95% CI of difference, adjustment is made for randomization strata (HCV-Infection status at baseline) if N \>= 5 in each treatment arm.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=31 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=32 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=36 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=38 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=37 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase
6 months
|
35.5 percentage of participants
Interval 18.6 to 52.3
|
15.6 percentage of participants
Interval 3.0 to 28.2
|
13.9 percentage of participants
Interval 2.6 to 25.2
|
21.1 percentage of participants
Interval 8.1 to 34.0
|
35.1 percentage of participants
Interval 19.8 to 50.5
|
|
Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase
12 months
|
35.5 percentage of participants
Interval 18.6 to 52.3
|
15.6 percentage of participants
Interval 3.0 to 28.2
|
13.9 percentage of participants
Interval 2.6 to 25.2
|
23.7 percentage of participants
Interval 10.2 to 37.2
|
37.8 percentage of participants
Interval 22.2 to 53.5
|
SECONDARY outcome
Timeframe: 6, 12 months (mth) posttransplantPopulation: ITT population, all randomized and transplanted participants. n = Participants with both baseline and postbaseline values.
The HbA1c test is important in diabetes as a long-term measure of control over blood glucose, where the glucose bound to hemoglobin during the past 3-4 months is measured. A baseline diabetes participant was one who had a medical history of diabetes or being under anti-diabetic medication at the time of the transplantation. BL = baseline, DM = Diabetes mellitus.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase
6 mo: DM at BL/DM at 6m (n=23, 14, 14, 19, 18)
|
6.1 Percentage of glycosylated hemoglobin
Standard Deviation 1.17
|
6.4 Percentage of glycosylated hemoglobin
Standard Deviation 1.02
|
5.9 Percentage of glycosylated hemoglobin
Standard Deviation 0.90
|
5.5 Percentage of glycosylated hemoglobin
Standard Deviation 1.04
|
5.4 Percentage of glycosylated hemoglobin
Standard Deviation 0.62
|
|
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase
12 mo: All participants (n=40, 35, 35, 44, 37)
|
6.0 Percentage of glycosylated hemoglobin
Standard Deviation 1.32
|
5.8 Percentage of glycosylated hemoglobin
Standard Deviation 1.03
|
5.7 Percentage of glycosylated hemoglobin
Standard Deviation 0.97
|
5.5 Percentage of glycosylated hemoglobin
Standard Deviation 0.76
|
5.8 Percentage of glycosylated hemoglobin
Standard Deviation 1.85
|
|
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase
12 mo: DM at BL (n=15, 11, 7, 11, 12)
|
6.9 Percentage of glycosylated hemoglobin
Standard Deviation 1.60
|
6.7 Percentage of glycosylated hemoglobin
Standard Deviation 1.40
|
6.7 Percentage of glycosylated hemoglobin
Standard Deviation 1.49
|
6.2 Percentage of glycosylated hemoglobin
Standard Deviation 0.96
|
6.5 Percentage of glycosylated hemoglobin
Standard Deviation 3.05
|
|
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase
12 mo: DM at BL/DM at 12 mth (n=23,13 ,11,18,20)
|
6.3 Percentage of glycosylated hemoglobin
Standard Deviation 1.58
|
6.6 Percentage of glycosylated hemoglobin
Standard Deviation 1.29
|
6.2 Percentage of glycosylated hemoglobin
Standard Deviation 1.40
|
6.0 Percentage of glycosylated hemoglobin
Standard Deviation 0.84
|
6.3 Percentage of glycosylated hemoglobin
Standard Deviation 2.39
|
|
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase
6 mo: All participants (n=39, 34, 38, 47, 35)
|
5.8 Percentage of glycosylated hemoglobin
Standard Deviation 1.07
|
5.8 Percentage of glycosylated hemoglobin
Standard Deviation 0.96
|
5.6 Percentage of glycosylated hemoglobin
Standard Deviation 0.75
|
5.4 Percentage of glycosylated hemoglobin
Standard Deviation 0.90
|
5.4 Percentage of glycosylated hemoglobin
Standard Deviation 0.84
|
|
Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase
6 mo: DM at BL (n=15, 12, 10, 12, 10)
|
6.5 Percentage of glycosylated hemoglobin
Standard Deviation 1.19
|
6.6 Percentage of glycosylated hemoglobin
Standard Deviation 1.02
|
6.1 Percentage of glycosylated hemoglobin
Standard Deviation 0.76
|
5.8 Percentage of glycosylated hemoglobin
Standard Deviation 1.19
|
5.4 Percentage of glycosylated hemoglobin
Standard Deviation 0.59
|
SECONDARY outcome
Timeframe: Day 1 (randomization) to 12 m + 8 week follow-up or ≤ 56 days after discontinuation of study medicationPopulation: ITT population: all randomized and transplanted participants
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
Discontinued due to AEs
|
7 participants
|
7 participants
|
12 participants
|
7 participants
|
18 participants
|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
Death
|
4 participants
|
4 participants
|
9 participants
|
1 participants
|
4 participants
|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
SAEs
|
28 participants
|
29 participants
|
37 participants
|
40 participants
|
35 participants
|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
Related SAEs
|
12 participants
|
11 participants
|
14 participants
|
16 participants
|
19 participants
|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
Discontinued due to SAEs
|
7 participants
|
6 participants
|
11 participants
|
4 participants
|
13 participants
|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
AEs
|
50 participants
|
48 participants
|
48 participants
|
53 participants
|
50 participants
|
|
Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase
Related AEs
|
45 participants
|
34 participants
|
33 participants
|
42 participants
|
42 participants
|
SECONDARY outcome
Timeframe: Day 1 (randomization) to 12 months or ≤ 56 days after discontinuation of study medicationPopulation: ITT population, all randomized and transplanted participants.
AE of of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial), serious infections
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Malignancies
|
1 participants
|
0 participants
|
2 participants
|
2 participants
|
2 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Post-transplant lymphoproliferative disorder
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Fungal infections
|
6 participants
|
9 participants
|
14 participants
|
6 participants
|
5 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Polyoma virus infections
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Herpes infections
|
3 participants
|
3 participants
|
4 participants
|
3 participants
|
2 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Hepatitis C virus recurrence
|
14 participants
|
7 participants
|
6 participants
|
13 participants
|
9 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Thrombotic and embolic events
|
3 participants
|
3 participants
|
7 participants
|
10 participants
|
5 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
All Infections
|
32 participants
|
39 participants
|
30 participants
|
31 participants
|
29 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Bacterial infections
|
5 participants
|
11 participants
|
11 participants
|
6 participants
|
13 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Viral infections
|
10 participants
|
11 participants
|
14 participants
|
9 participants
|
7 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Cytomegalovirus infections
|
5 participants
|
4 participants
|
10 participants
|
4 participants
|
1 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Serious infections
|
11 participants
|
12 participants
|
13 participants
|
12 participants
|
12 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Autoimmune events
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
2 participants
|
|
Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase
Acute peri-infusional events
|
5 participants
|
1 participants
|
0 participants
|
NA participants
|
NA participants
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 2, 4, 8, 12 weeks, and every 4 weeks for week 16 to 52Population: ITT population, all randomized and transplanted participants. n= participants with all observations.
Low hemoglobin: \<8 g/dL; Low platelet count: \<50\*10\^9 C/L; Low leukocytes: \<2.0 \*10\^3 c/µL; Low lymphocytes (absolute): \<0.5\*10\^3 c/µL; Low neutrophils (absolute): \<1.0\*10\^3 Cc/µL.
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase
Low Hemoglobin: (n=48, 46, 44, 52, 50)
|
2 participants
|
6 participants
|
2 participants
|
0 participants
|
6 participants
|
|
Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase
Low Platelets: (n=48, 46, 43, 52, 50)
|
0 participants
|
1 participants
|
4 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase
Low Leukocytes : (n=48, 46, 44, 52, 50)
|
6 participants
|
6 participants
|
5 participants
|
4 participants
|
3 participants
|
|
Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase
Low Absolute Neutrophils : (n=48, 46, 44, 52, 50)
|
6 participants
|
4 participants
|
4 participants
|
8 participants
|
1 participants
|
|
Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase
Low Absolute Lymphocyte: (n=48, 46, 44, 52, 50)
|
29 participants
|
18 participants
|
26 participants
|
17 participants
|
16 participants
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), 4, 12, 24, 52 weeksPopulation: ITT population, all randomized and transplanted participants. n= participants with all observations.
ULN= upper limit of normal; Normal ranges are provided by the central laboratory and may vary according to sex and age. High alkaline phosphatase (ALP): \>5.0\*ULN U/L; High alanine aminotransferase (ALT): \>5.0\*ULN U/L; High aspartate aminotransferase (AST): \>5.0\*ULN U/L; High direct bilirubin: \>3.0 \* ULN mg/dL; High g-glutamyl transferase (GGT): \>5.0\*ULN U/L; High total bilirubin: \>3.0\*ULN mg/dL; High creatinine: \> 3.0\*ULN mg/dL
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High ALP: (n=48, 47, 44, 53, 50)
|
5 participants
|
6 participants
|
6 participants
|
4 participants
|
6 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High ALT: (n=48, 47, 44, 53, 50)
|
16 participants
|
18 participants
|
19 participants
|
16 participants
|
9 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High AST: (n=48, 47, 44, 53, 50)
|
9 participants
|
14 participants
|
16 participants
|
8 participants
|
2 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High Direct Bilirubin: (n=48, 47, 44, 53, 50)
|
15 participants
|
18 participants
|
19 participants
|
20 participants
|
16 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High GGT: (n=48, 47, 44, 53, 50)
|
25 participants
|
24 participants
|
24 participants
|
27 participants
|
22 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High Total Bilirubin: (n=48, 47, 44, 53, 50)
|
9 participants
|
13 participants
|
16 participants
|
12 participants
|
10 participants
|
|
Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase
High Creatinine: (n=47, 44, 44, 53, 50)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), Weeks 4, 12, 24, and 52Population: ITT population, all randomized and transplanted participants. n= participants with all observations.
Low total calcium: \<7 mg/dL; High total calcium: \>12.5 mg/dL ; Low bicarbonate: \<11 mEq/L; Low serum potassium: \<3.0 mEq/L; High serum potassium:\>6.0 mEq/L; High serum magnesium: \>2.46 mEq/L; Low serum magnesium:\<0.8 mEq/L; Low serum sodium: \<130 mEq/L; High serum sodium: \>155 mEq/L; Low inorganic phosphorus: \<2.0 mg/dL; Low albumin: \<2 g/dL; High uric acid: \>10 mg/dL
Outcome measures
| Measure |
Group 1: Basiliximab+Belatacept (MI) + MMF
n=50 Participants
Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 2: Belatacept (MI) + MMF
n=48 Participants
Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 3: Belatacept (LI) + MMF
n=49 Participants
Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST\]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE)
|
Group 4: Tacrolimus + MMF
n=53 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE)
|
Group 5: Tacrolimus
n=50 Participants
Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE)
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
High Total Calcium (n=48, 47, 44, 53, 50)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
High Serum Potassium (n=48, 47, 44, 53, 50)
|
1 participants
|
0 participants
|
1 participants
|
2 participants
|
1 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
High Serum Magnesium (n=48, 47, 44, 53, 50)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Total Calcium (n=48, 47, 44, 53, 50)
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Bicarbonate (n=47, 47, 44, 53, 50)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Serum Potassium (n=48, 47, 44, 53, 50)
|
0 participants
|
2 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Serum Magnesium (n=48, 47, 44, 53, 50)
|
2 participants
|
0 participants
|
2 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Serum Sodium (n=48, 47, 44, 53, 50)
|
3 participants
|
2 participants
|
2 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
High Serum Sodium (n=48, 47, 44, 53, 50)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Inorganic Phosphorus (n=48, 47, 44, 53, 50)
|
0 participants
|
2 participants
|
1 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
Low Albumin (n=47, 47, 45, 53, 50)
|
2 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase
High Uric Acid (n=48, 47, 44, 53, 50)
|
2 participants
|
1 participants
|
2 participants
|
5 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Baseline (pretransplant), Week 52Population: ECG data was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 3 and 12Population: Protein creatinine ratio change was not analyzed
Outcome measures
Outcome data not reported
Adverse Events
Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF)
Serious events: 18 serious events
Other events: 29 other events
Deaths: 0 deaths
MI+MMF
Serious events: 17 serious events
Other events: 23 other events
Deaths: 0 deaths
Belaticept (LI) + MMF
Serious events: 22 serious events
Other events: 27 other events
Deaths: 0 deaths
Tacrolimus
Serious events: 21 serious events
Other events: 25 other events
Deaths: 0 deaths
Tacrolimus + MMF
Serious events: 29 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF)
n=30 participants at risk
|
MI+MMF
n=24 participants at risk
|
Belaticept (LI) + MMF
n=27 participants at risk
|
Tacrolimus
n=26 participants at risk
|
Tacrolimus + MMF
n=38 participants at risk
|
|---|---|---|---|---|---|
|
Hepatobiliary disorders
Bile duct obstruction
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Biliary abscess
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Nervous system disorders
Encephalomalacia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Localised intraabdominal fluid collection
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Renal and urinary disorders
Renal failure acute
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
15.4%
4/26
|
7.9%
3/38
|
|
Hepatobiliary disorders
Biloma
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Investigations
Blood glucose increased
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Infections and infestations
Bronchitis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
General disorders
Device leakage
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Infections and infestations
Epstein-Barr virus infection
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Investigations
Haematocrit decreased
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Fractured sacrum
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
6.7%
2/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
7.9%
3/38
|
|
General disorders
Medical device complication
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Infections and infestations
Parvovirus infection
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Eye disorders
Retinal vein occlusion
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Infections and infestations
Sepsis
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Tracheobronchitis
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Nervous system disorders
Tremor
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Abdominal abscess
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Psychiatric disorders
Alcoholism
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Vascular disorders
Artery dissection
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Coeliac artery stenosis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
General disorders
General physical health deterioration
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Liver abscess
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Blood and lymphatic system disorders
Normochromic normocytic anaemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Obesity
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal cancer metastatic
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Oesophageal candidiasis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Pneumonia
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
19.2%
5/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Biliary ischaemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Volvulus
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
11.5%
3/26
|
0.00%
0/38
|
|
Infections and infestations
Abscess limb
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Vascular disorders
Arterial insufficiency
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Cytomegalovirus infection
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Reproductive system and breast disorders
Epididymitis
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Nervous system disorders
Headache
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Hepatic artery thrombosis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Respiratory, thoracic and mediastinal disorders
Hepatopulmonary syndrome
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
General disorders
Hernia
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Hypotension
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Influenza
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Investigations
Liver function test abnormal
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
10.5%
4/38
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Bile duct stenosis
|
10.0%
3/30
|
12.5%
3/24
|
0.00%
0/27
|
7.7%
2/26
|
5.3%
2/38
|
|
General disorders
Chest pain
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Cholangitis
|
6.7%
2/30
|
8.3%
2/24
|
3.7%
1/27
|
7.7%
2/26
|
13.2%
5/38
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Haemobilia
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant recurrent
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Infections and infestations
Hepatitis B
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Hepatitis C
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Shock haemorrhagic
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Eye disorders
Visual impairment
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Psychiatric disorders
Agitation
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Bacterial infection
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Infections and infestations
Cellulitis
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Cholestasis
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Cytomegalovirus viraemia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Dehydration
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Reproductive system and breast disorders
Gynaecomastia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Hepatic artery stenosis
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Hepatic haemorrhage
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Incision site cellulitis
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Influenza like illness
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Lymphopenia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Meningitis aseptic
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Psychiatric disorders
Mental disorder
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
General disorders
Oedema peripheral
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleura carcinoma
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Eye disorders
Retinal detachment
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Investigations
Transaminases increased
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Immune system disorders
Transplant rejection
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Urinary tract infection
|
3.3%
1/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Varicella
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Psychiatric disorders
Confusional state
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Device related infection
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Groin abscess
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Hepatic haematoma
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Pancreatitis
|
10.0%
3/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Pulmonary sepsis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Psychiatric disorders
Transient psychosis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Vascular pseudoaneurysm
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Wound infection
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Acute hepatic failure
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Biliary tract disorder
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Investigations
Body temperature increased
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Nervous system disorders
Convulsion
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Infections and infestations
Cystitis
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Psychiatric disorders
Depression
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Drug dispensing error
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Epstein-Barr virus associated lymphoproliferative disorder
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Gastrointestinal infection
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Hepatitis E
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Ileus
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
General disorders
Multi-organ failure
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Portal vein stenosis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Pyrexia
|
6.7%
2/30
|
8.3%
2/24
|
3.7%
1/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Salivary gland fistula
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tonsil cancer
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Urosepsis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
Other adverse events
| Measure |
Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF)
n=30 participants at risk
|
MI+MMF
n=24 participants at risk
|
Belaticept (LI) + MMF
n=27 participants at risk
|
Tacrolimus
n=26 participants at risk
|
Tacrolimus + MMF
n=38 participants at risk
|
|---|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Blood and lymphatic system disorders
Anaemia
|
43.3%
13/30
|
20.8%
5/24
|
40.7%
11/27
|
42.3%
11/26
|
36.8%
14/38
|
|
Gastrointestinal disorders
Ascites
|
30.0%
9/30
|
16.7%
4/24
|
22.2%
6/27
|
19.2%
5/26
|
23.7%
9/38
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
16.7%
5/30
|
4.2%
1/24
|
11.1%
3/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Cardiac disorders
Atrial fibrillation
|
6.7%
2/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Bloody discharge
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Fatigue
|
36.7%
11/30
|
8.3%
2/24
|
14.8%
4/27
|
46.2%
12/26
|
31.6%
12/38
|
|
Infections and infestations
Fungal skin infection
|
6.7%
2/30
|
4.2%
1/24
|
11.1%
3/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Gait disturbance
|
3.3%
1/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/30
|
8.3%
2/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.7%
2/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
10.0%
3/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
3/30
|
8.3%
2/24
|
11.1%
3/27
|
15.4%
4/26
|
5.3%
2/38
|
|
Injury, poisoning and procedural complications
Incision site erythema
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Psychiatric disorders
Insomnia
|
23.3%
7/30
|
20.8%
5/24
|
29.6%
8/27
|
34.6%
9/26
|
21.1%
8/38
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Psychiatric disorders
Mental status changes
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
6/30
|
12.5%
3/24
|
33.3%
9/27
|
7.7%
2/26
|
26.3%
10/38
|
|
Gastrointestinal disorders
Nausea
|
26.7%
8/30
|
29.2%
7/24
|
29.6%
8/27
|
34.6%
9/26
|
34.2%
13/38
|
|
General disorders
Oedema
|
6.7%
2/30
|
20.8%
5/24
|
11.1%
3/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
6.7%
2/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Investigations
Platelet count decreased
|
6.7%
2/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Infections and infestations
Pneumonia
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
11.5%
3/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
0.00%
0/30
|
8.3%
2/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Eye disorders
Visual acuity reduced
|
10.0%
3/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
6/30
|
20.8%
5/24
|
14.8%
4/27
|
30.8%
8/26
|
15.8%
6/38
|
|
Investigations
Blood glucose increased
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
13.2%
5/38
|
|
Infections and infestations
Bronchitis
|
0.00%
0/30
|
8.3%
2/24
|
3.7%
1/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Constipation
|
40.0%
12/30
|
29.2%
7/24
|
37.0%
10/27
|
38.5%
10/26
|
36.8%
14/38
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.3%
4/30
|
16.7%
4/24
|
11.1%
3/27
|
23.1%
6/26
|
15.8%
6/38
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.00%
0/30
|
12.5%
3/24
|
7.4%
2/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/30
|
8.3%
2/24
|
14.8%
4/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Nervous system disorders
Facial paresis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma of liver
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Haemorrhoids
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.3%
1/30
|
8.3%
2/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
13.3%
4/30
|
8.3%
2/24
|
7.4%
2/27
|
3.8%
1/26
|
10.5%
4/38
|
|
Nervous system disorders
Neuropathy peripheral
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Renal and urinary disorders
Nocturia
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Infections and infestations
Oral herpes
|
6.7%
2/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/30
|
8.3%
2/24
|
18.5%
5/27
|
7.7%
2/26
|
18.4%
7/38
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
5/30
|
20.8%
5/24
|
18.5%
5/27
|
26.9%
7/26
|
15.8%
6/38
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
6.7%
2/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Nervous system disorders
Tremor
|
3.3%
1/30
|
12.5%
3/24
|
7.4%
2/27
|
38.5%
10/26
|
36.8%
14/38
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Abdominal hernia
|
6.7%
2/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Infections and infestations
Bacteraemia
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Investigations
Blood pressure increased
|
6.7%
2/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Eye disorders
Cataract
|
6.7%
2/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Infections and infestations
Clostridial infection
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
40.0%
12/30
|
8.3%
2/24
|
29.6%
8/27
|
11.5%
3/26
|
15.8%
6/38
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
2/30
|
4.2%
1/24
|
11.1%
3/27
|
11.5%
3/26
|
7.9%
3/38
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
5/30
|
20.8%
5/24
|
22.2%
6/27
|
26.9%
7/26
|
13.2%
5/38
|
|
Infections and infestations
Enterococcal infection
|
0.00%
0/30
|
0.00%
0/24
|
11.1%
3/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Investigations
Gamma-glutamyltransferase increased
|
3.3%
1/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Haematoma
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
3.3%
1/30
|
0.00%
0/24
|
11.1%
3/27
|
11.5%
3/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.7%
2/30
|
4.2%
1/24
|
14.8%
4/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Nervous system disorders
Hyporeflexia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
General disorders
Irritability
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Nervous system disorders
Lethargy
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Gastrointestinal disorders
Localised intraabdominal fluid collection
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Vascular disorders
Lymphocele
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/30
|
0.00%
0/24
|
11.1%
3/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Injury, poisoning and procedural complications
Procedural pain
|
33.3%
10/30
|
20.8%
5/24
|
33.3%
9/27
|
34.6%
9/26
|
31.6%
12/38
|
|
Renal and urinary disorders
Proteinuria
|
13.3%
4/30
|
4.2%
1/24
|
3.7%
1/27
|
15.4%
4/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
3.3%
1/30
|
4.2%
1/24
|
11.1%
3/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Renal and urinary disorders
Renal failure acute
|
6.7%
2/30
|
0.00%
0/24
|
7.4%
2/27
|
7.7%
2/26
|
21.1%
8/38
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/30
|
4.2%
1/24
|
3.7%
1/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Investigations
Urine output decreased
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
15.4%
4/26
|
5.3%
2/38
|
|
Investigations
White blood cell count increased
|
0.00%
0/30
|
0.00%
0/24
|
11.1%
3/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
10/30
|
12.5%
3/24
|
29.6%
8/27
|
34.6%
9/26
|
34.2%
13/38
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.3%
4/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
10/30
|
29.2%
7/24
|
33.3%
9/27
|
23.1%
6/26
|
28.9%
11/38
|
|
Investigations
Bacterial test positive
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Investigations
Blood potassium increased
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
11.5%
3/26
|
2.6%
1/38
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
19.2%
5/26
|
5.3%
2/38
|
|
Infections and infestations
Candidiasis
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/30
|
12.5%
3/24
|
7.4%
2/27
|
0.00%
0/26
|
13.2%
5/38
|
|
Infections and infestations
Cytomegalovirus infection
|
6.7%
2/30
|
12.5%
3/24
|
7.4%
2/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Nervous system disorders
Dizziness
|
20.0%
6/30
|
4.2%
1/24
|
14.8%
4/27
|
11.5%
3/26
|
10.5%
4/38
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Eye disorders
Eye pruritus
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
11.5%
3/26
|
0.00%
0/38
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Nervous system disorders
Headache
|
40.0%
12/30
|
16.7%
4/24
|
33.3%
9/27
|
53.8%
14/26
|
26.3%
10/38
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/30
|
12.5%
3/24
|
7.4%
2/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
16.7%
5/30
|
8.3%
2/24
|
11.1%
3/27
|
30.8%
8/26
|
21.1%
8/38
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
10.0%
3/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Vascular disorders
Hypotension
|
16.7%
5/30
|
4.2%
1/24
|
25.9%
7/27
|
23.1%
6/26
|
18.4%
7/38
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Incision site complication
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Infections and infestations
Influenza
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Blood and lymphatic system disorders
Leukocytosis
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Investigations
Liver function test abnormal
|
20.0%
6/30
|
4.2%
1/24
|
11.1%
3/27
|
34.6%
9/26
|
18.4%
7/38
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Psychiatric disorders
Mood swings
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
16.7%
5/30
|
12.5%
3/24
|
11.1%
3/27
|
7.7%
2/26
|
18.4%
7/38
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
15.4%
4/26
|
7.9%
3/38
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/30
|
4.2%
1/24
|
3.7%
1/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
5/30
|
4.2%
1/24
|
11.1%
3/27
|
30.8%
8/26
|
26.3%
10/38
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Investigations
Staphylococcus test positive
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Toothache
|
6.7%
2/30
|
4.2%
1/24
|
3.7%
1/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
6.7%
2/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.7%
2/30
|
4.2%
1/24
|
7.4%
2/27
|
11.5%
3/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
10.5%
4/38
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
11.5%
3/26
|
2.6%
1/38
|
|
Gastrointestinal disorders
Abdominal tenderness
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Hepatobiliary disorders
Bile duct stenosis
|
10.0%
3/30
|
0.00%
0/24
|
7.4%
2/27
|
15.4%
4/26
|
2.6%
1/38
|
|
Investigations
Breath sounds abnormal
|
10.0%
3/30
|
8.3%
2/24
|
11.1%
3/27
|
11.5%
3/26
|
7.9%
3/38
|
|
Investigations
C-reactive protein increased
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
General disorders
Catheter site pain
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Chest pain
|
6.7%
2/30
|
16.7%
4/24
|
14.8%
4/27
|
7.7%
2/26
|
2.6%
1/38
|
|
General disorders
Chills
|
10.0%
3/30
|
0.00%
0/24
|
11.1%
3/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Hepatobiliary disorders
Cholangitis
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
10.5%
4/38
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
6.7%
2/30
|
16.7%
4/24
|
7.4%
2/27
|
11.5%
3/26
|
23.7%
9/38
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
12/30
|
41.7%
10/24
|
37.0%
10/27
|
42.3%
11/26
|
60.5%
23/38
|
|
Injury, poisoning and procedural complications
Excoriation
|
3.3%
1/30
|
4.2%
1/24
|
11.1%
3/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
3.3%
1/30
|
0.00%
0/24
|
7.4%
2/27
|
11.5%
3/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Flatulence
|
13.3%
4/30
|
8.3%
2/24
|
3.7%
1/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Vascular disorders
Flushing
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
General disorders
Generalised oedema
|
3.3%
1/30
|
4.2%
1/24
|
11.1%
3/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Renal and urinary disorders
Haematuria
|
6.7%
2/30
|
4.2%
1/24
|
3.7%
1/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Infections and infestations
Hepatitis C
|
6.7%
2/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
13.3%
4/30
|
4.2%
1/24
|
14.8%
4/27
|
23.1%
6/26
|
21.1%
8/38
|
|
General disorders
Impaired healing
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Infections and infestations
Laryngitis
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Nervous system disorders
Migraine
|
0.00%
0/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
3.3%
1/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.3%
1/30
|
8.3%
2/24
|
14.8%
4/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/30
|
8.3%
2/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
5/30
|
8.3%
2/24
|
14.8%
4/27
|
19.2%
5/26
|
13.2%
5/38
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
19.2%
5/26
|
5.3%
2/38
|
|
Infections and infestations
Respiratory tract infection
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Infections and infestations
Sinusitis
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Gastrointestinal disorders
Varices oesophageal
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Eye disorders
Vision blurred
|
10.0%
3/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Eye disorders
Visual impairment
|
6.7%
2/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Investigations
Weight increased
|
16.7%
5/30
|
25.0%
6/24
|
7.4%
2/27
|
23.1%
6/26
|
7.9%
3/38
|
|
Investigations
White blood cell count decreased
|
10.0%
3/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
3/30
|
12.5%
3/24
|
11.1%
3/27
|
15.4%
4/26
|
10.5%
4/38
|
|
Psychiatric disorders
Agitation
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Investigations
Aspartate aminotransferase increased
|
3.3%
1/30
|
8.3%
2/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Asthenia
|
13.3%
4/30
|
12.5%
3/24
|
14.8%
4/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Investigations
Blood bilirubin increased
|
13.3%
4/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Cellulitis
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Cholestasis
|
6.7%
2/30
|
0.00%
0/24
|
7.4%
2/27
|
11.5%
3/26
|
15.8%
6/38
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Infections and infestations
Ear infection
|
0.00%
0/30
|
8.3%
2/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/30
|
12.5%
3/24
|
11.1%
3/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Investigations
Enterococcus test positive
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Fall
|
3.3%
1/30
|
8.3%
2/24
|
3.7%
1/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Gastrointestinal disorders
Gastritis
|
6.7%
2/30
|
4.2%
1/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Psychiatric disorders
Hallucination
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Hepatobiliary disorders
Hepatic artery stenosis
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Hepatic steatosis
|
0.00%
0/30
|
4.2%
1/24
|
3.7%
1/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Vascular disorders
Hypertension
|
16.7%
5/30
|
25.0%
6/24
|
22.2%
6/27
|
42.3%
11/26
|
42.1%
16/38
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Increased tendency to bruise
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
0.00%
0/38
|
|
General disorders
Influenza like illness
|
3.3%
1/30
|
4.2%
1/24
|
3.7%
1/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Blood and lymphatic system disorders
Leukopenia
|
26.7%
8/30
|
37.5%
9/24
|
18.5%
5/27
|
11.5%
3/26
|
34.2%
13/38
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
10.0%
3/30
|
4.2%
1/24
|
11.1%
3/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
General disorders
Oedema peripheral
|
36.7%
11/30
|
29.2%
7/24
|
37.0%
10/27
|
38.5%
10/26
|
50.0%
19/38
|
|
General disorders
Pain
|
13.3%
4/30
|
8.3%
2/24
|
3.7%
1/27
|
3.8%
1/26
|
10.5%
4/38
|
|
Nervous system disorders
Paraesthesia
|
10.0%
3/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
7.9%
3/38
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
23.3%
7/30
|
20.8%
5/24
|
22.2%
6/27
|
30.8%
8/26
|
26.3%
10/38
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/30
|
0.00%
0/24
|
11.1%
3/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Investigations
Transaminases increased
|
10.0%
3/30
|
4.2%
1/24
|
11.1%
3/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
5/30
|
8.3%
2/24
|
14.8%
4/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Infections and infestations
Urinary tract infection
|
23.3%
7/30
|
16.7%
4/24
|
29.6%
8/27
|
7.7%
2/26
|
13.2%
5/38
|
|
Ear and labyrinth disorders
Vertigo
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Gastrointestinal disorders
Abdominal distension
|
23.3%
7/30
|
12.5%
3/24
|
11.1%
3/27
|
7.7%
2/26
|
13.2%
5/38
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/30
|
8.3%
2/24
|
3.7%
1/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Anastomotic stenosis
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
0.00%
0/30
|
0.00%
0/24
|
11.1%
3/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Investigations
Blood alkaline phosphatase increased
|
10.0%
3/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Investigations
Blood triglycerides increased
|
6.7%
2/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Coagulopathy
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Psychiatric disorders
Confusional state
|
10.0%
3/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Infections and infestations
Device related infection
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
11.5%
3/26
|
0.00%
0/38
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Fluid overload
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Hepatic haematoma
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Vascular disorders
Hot flush
|
13.3%
4/30
|
4.2%
1/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
36.7%
11/30
|
20.8%
5/24
|
33.3%
9/27
|
19.2%
5/26
|
23.7%
9/38
|
|
Injury, poisoning and procedural complications
Incision site pain
|
16.7%
5/30
|
8.3%
2/24
|
7.4%
2/27
|
15.4%
4/26
|
15.8%
6/38
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
General disorders
Malaise
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
10.5%
4/38
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
3/30
|
0.00%
0/24
|
7.4%
2/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Renal and urinary disorders
Nephrolithiasis
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.0%
3/30
|
16.7%
4/24
|
11.1%
3/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
3.3%
1/30
|
8.3%
2/24
|
3.7%
1/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/30
|
8.3%
2/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
13.3%
4/30
|
8.3%
2/24
|
3.7%
1/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
19.2%
5/26
|
13.2%
5/38
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
13.3%
4/30
|
4.2%
1/24
|
11.1%
3/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Psychiatric disorders
Transient psychosis
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Renal and urinary disorders
Urinary incontinence
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Injury, poisoning and procedural complications
Wound complication
|
10.0%
3/30
|
0.00%
0/24
|
3.7%
1/27
|
3.8%
1/26
|
7.9%
3/38
|
|
Infections and infestations
Wound infection
|
13.3%
4/30
|
4.2%
1/24
|
11.1%
3/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Nervous system disorders
Amnesia
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Psychiatric disorders
Anxiety
|
23.3%
7/30
|
4.2%
1/24
|
11.1%
3/27
|
23.1%
6/26
|
18.4%
7/38
|
|
Investigations
Blood creatinine increased
|
16.7%
5/30
|
4.2%
1/24
|
7.4%
2/27
|
23.1%
6/26
|
21.1%
8/38
|
|
Investigations
Blood magnesium decreased
|
3.3%
1/30
|
0.00%
0/24
|
0.00%
0/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Investigations
Body temperature increased
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Investigations
Clostridium test positive
|
0.00%
0/30
|
0.00%
0/24
|
7.4%
2/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Nervous system disorders
Convulsion
|
0.00%
0/30
|
4.2%
1/24
|
3.7%
1/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Infections and infestations
Cystitis
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Psychiatric disorders
Depression
|
33.3%
10/30
|
16.7%
4/24
|
7.4%
2/27
|
23.1%
6/26
|
13.2%
5/38
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
3.3%
1/30
|
8.3%
2/24
|
7.4%
2/27
|
0.00%
0/26
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.7%
2/30
|
0.00%
0/24
|
3.7%
1/27
|
15.4%
4/26
|
7.9%
3/38
|
|
Investigations
Hepatic enzyme increased
|
16.7%
5/30
|
16.7%
4/24
|
14.8%
4/27
|
3.8%
1/26
|
10.5%
4/38
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
6.7%
2/30
|
8.3%
2/24
|
3.7%
1/27
|
0.00%
0/26
|
5.3%
2/38
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
3.3%
1/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
13.3%
4/30
|
0.00%
0/24
|
14.8%
4/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
20.0%
6/30
|
37.5%
9/24
|
29.6%
8/27
|
11.5%
3/26
|
21.1%
8/38
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
6.7%
2/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
2.6%
1/38
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/30
|
8.3%
2/24
|
3.7%
1/27
|
7.7%
2/26
|
5.3%
2/38
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
0.00%
0/26
|
7.9%
3/38
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.7%
2/30
|
12.5%
3/24
|
3.7%
1/27
|
11.5%
3/26
|
7.9%
3/38
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.3%
1/30
|
4.2%
1/24
|
7.4%
2/27
|
0.00%
0/26
|
2.6%
1/38
|
|
Renal and urinary disorders
Oliguria
|
6.7%
2/30
|
4.2%
1/24
|
3.7%
1/27
|
15.4%
4/26
|
2.6%
1/38
|
|
Infections and infestations
Peritonitis bacterial
|
0.00%
0/30
|
0.00%
0/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/30
|
4.2%
1/24
|
0.00%
0/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Injury, poisoning and procedural complications
Post procedural discharge
|
6.7%
2/30
|
0.00%
0/24
|
11.1%
3/27
|
0.00%
0/26
|
5.3%
2/38
|
|
General disorders
Pyrexia
|
36.7%
11/30
|
33.3%
8/24
|
37.0%
10/27
|
30.8%
8/26
|
23.7%
9/38
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
3.3%
1/30
|
4.2%
1/24
|
0.00%
0/27
|
7.7%
2/26
|
2.6%
1/38
|
|
Reproductive system and breast disorders
Scrotal oedema
|
6.7%
2/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
5.3%
2/38
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/30
|
4.2%
1/24
|
7.4%
2/27
|
11.5%
3/26
|
5.3%
2/38
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/30
|
8.3%
2/24
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/38
|
|
Cardiac disorders
Tachycardia
|
13.3%
4/30
|
0.00%
0/24
|
14.8%
4/27
|
7.7%
2/26
|
15.8%
6/38
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
23.3%
7/30
|
25.0%
6/24
|
11.1%
3/27
|
3.8%
1/26
|
15.8%
6/38
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/30
|
0.00%
0/24
|
3.7%
1/27
|
7.7%
2/26
|
0.00%
0/38
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
6/30
|
16.7%
4/24
|
14.8%
4/27
|
30.8%
8/26
|
26.3%
10/38
|
|
Investigations
Weight decreased
|
10.0%
3/30
|
12.5%
3/24
|
3.7%
1/27
|
11.5%
3/26
|
10.5%
4/38
|
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