Trial Outcomes & Findings for Efficacy, Tolerability and Safety of Early Introduction of Everolimus, Reduced Calcineurin Inhibitors and Early Steroid Elimination Compared to Standard CNI, Mycophenolate Mofetil and Steroid Regimen in Paediatric Renal Transplant Recipients (NCT NCT01544491)
NCT ID: NCT01544491
Last Updated: 2019-05-31
Results Overview
To estimate the rate of the composite efficacy endpoint of biopsy-proven acute rejection (BPAR), graft loss or death at 12 months post transplantation in primary paediatric kidney transplant recipients converted at 4-6 weeks post-transplantation from MMF + standard TAC regimen and steroids, to everolimus + reduced dose TAC regimen and steroid withdrawal at 6 months, versus continuation of MMF + standard TAC regimen and steroids.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
106 participants
Primary outcome timeframe
12 months, 36 months
Results posted on
2019-05-31
Participant Flow
Full Analysis set (FAS) 106 enrolled and randomized patients except misrandomized Per Protocol set (PPS) 90 patients in the FAS without major protocol deviations Safety set (SAF) 106 randomized patients who received at least one dose of study drug
Participant milestones
| Measure |
EVR+rTAC
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Overall Study
STARTED
|
52
|
54
|
|
Overall Study
COMPLETED
|
47
|
51
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
EVR+rTAC
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
administrative problems
|
2
|
0
|
Baseline Characteristics
Efficacy, Tolerability and Safety of Early Introduction of Everolimus, Reduced Calcineurin Inhibitors and Early Steroid Elimination Compared to Standard CNI, Mycophenolate Mofetil and Steroid Regimen in Paediatric Renal Transplant Recipients
Baseline characteristics by cohort
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
Total
n=106 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
1 to <11 years
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Age, Customized
11 <= 18 years
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
29 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
42 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 months, 36 monthsPopulation: Full Analysis set (12 months and 36 months) Results given as number of participants with composite efficacy failures
To estimate the rate of the composite efficacy endpoint of biopsy-proven acute rejection (BPAR), graft loss or death at 12 months post transplantation in primary paediatric kidney transplant recipients converted at 4-6 weeks post-transplantation from MMF + standard TAC regimen and steroids, to everolimus + reduced dose TAC regimen and steroid withdrawal at 6 months, versus continuation of MMF + standard TAC regimen and steroids.
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Number of Participants Having Reached the Composite Efficacy Endpoint of Biopsy-proven Acute Rejection
12 months
|
5 Participants
|
3 Participants
|
|
Number of Participants Having Reached the Composite Efficacy Endpoint of Biopsy-proven Acute Rejection
36 months
|
5 Participants
|
5 Participants
|
PRIMARY outcome
Timeframe: 12 months and 36 months post-transplantationPopulation: Full Analysis set 12 months and 36 months
To evaluate renal function assessed by Glomerular Filtration Rate (eGFR) estimated by the Schwartz Formula (abbreviated) (Schwartz, 2009).
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
To Evaluate Renal Function, Assessed by Glomerular Filtration Rate (eGFR) and Estimated by the Schwartz Formula (Abbreviated), at Month 12 and 36
12 months
|
76.7 mL/min/1.73m2
Standard Error 3.66
|
71.7 mL/min/1.73m2
Standard Error 3.56
|
|
To Evaluate Renal Function, Assessed by Glomerular Filtration Rate (eGFR) and Estimated by the Schwartz Formula (Abbreviated), at Month 12 and 36
36 months
|
68.1 mL/min/1.73m2
Standard Error 3.45
|
67.3 mL/min/1.73m2
Standard Error 3.54
|
SECONDARY outcome
Timeframe: at 12 and 36 months post-transplantationPopulation: full Analysis set 36 month analysis Results given as number of participants with composite efficacy failures
To evaluate the proportion of patients with the following efficacy events: Biopsy Proven Acute Rejection (BPAR), graft loss or death. The efficacy events will be descriptively summarized by treatment group.
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Composite Efficacy Endpoint
month 12 composite efficacy endpoint
|
5 Participants
|
3 Participants
|
|
Composite Efficacy Endpoint
graft loss 12 months
|
0 Participants
|
0 Participants
|
|
Composite Efficacy Endpoint
death 12 months
|
0 Participants
|
0 Participants
|
|
Composite Efficacy Endpoint
acute rejection 12 months
|
5 Participants
|
4 Participants
|
|
Composite Efficacy Endpoint
treated acute rejection 12 months
|
5 Participants
|
4 Participants
|
|
Composite Efficacy Endpoint
Biopsy proven acute rejection 12 months
|
5 Participants
|
3 Participants
|
|
Composite Efficacy Endpoint
treated Biopsy proven acute rejection 12 months
|
5 Participants
|
3 Participants
|
|
Composite Efficacy Endpoint
month 36 composite efficacy endpoint
|
5 Participants
|
5 Participants
|
|
Composite Efficacy Endpoint
graft loss 36 months
|
1 Participants
|
2 Participants
|
|
Composite Efficacy Endpoint
death 36 months
|
0 Participants
|
0 Participants
|
|
Composite Efficacy Endpoint
acute rejection 36 months
|
5 Participants
|
7 Participants
|
|
Composite Efficacy Endpoint
Biopsy proven acute rejection 36 months
|
5 Participants
|
5 Participants
|
|
Composite Efficacy Endpoint
treated Biopsy proven acute rejection 36 months
|
5 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: month 12, month 36Population: full Analysis set 36 months
T-cell mediated rejection severity : Type IA - Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising \> 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 12 grade IA
|
3 Participants
|
1 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 12 grade IB
|
1 Participants
|
0 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 12 grade IIA
|
0 Participants
|
2 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 12 grade IIB
|
0 Participants
|
0 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 12 grade III
|
0 Participants
|
0 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 36 grade IA
|
3 Participants
|
1 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 36 grade IB
|
2 Participants
|
0 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 36 grade IIA
|
0 Participants
|
1 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 36 grade IIB
|
0 Participants
|
1 Participants
|
|
To Evaluate the Severity of BPAR (Acute T-cell Mediated Rejection Only) (Banff 2009)
month 36 grade III
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: full Analysis set, 36 month analysis
Time to incidence of Event, given in terms of number of participants with an Event according to time interval up to 36 months
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
To Evaluate the Time to Event of BPAR
day 1-7
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 8-14
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 15-28
|
1 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 29-56
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 57-84
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 85-150
|
2 Participants
|
2 Participants
|
|
To Evaluate the Time to Event of BPAR
day 151- 240
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 241-330
|
1 Participants
|
2 Participants
|
|
To Evaluate the Time to Event of BPAR
day 331- 510
|
0 Participants
|
1 Participants
|
|
To Evaluate the Time to Event of BPAR
day 511-690
|
1 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 691-870
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
day 871-1050
|
0 Participants
|
0 Participants
|
|
To Evaluate the Time to Event of BPAR
after day 1050
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: at 12 and 36 months post-transplantationPopulation: Full Analysis set
To evaluate the proportion of patients with the following efficacy events: biopsy proven antibody mediated rejection/Steroid resistant BPAR and BPAR treated with T cell depleting therapy.
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Incidence of Biopsy Proven Antibody Mediated Rejection.
patients with BPAR at 12 months
|
7 Participants
|
8 Participants
|
|
Incidence of Biopsy Proven Antibody Mediated Rejection.
BPAR Steroid resistant,12 months
|
1 Participants
|
0 Participants
|
|
Incidence of Biopsy Proven Antibody Mediated Rejection.
BPAR, T Cell depleting therapy 12 months
|
1 Participants
|
1 Participants
|
|
Incidence of Biopsy Proven Antibody Mediated Rejection.
patients with BPAR at 36 months
|
6 Participants
|
12 Participants
|
|
Incidence of Biopsy Proven Antibody Mediated Rejection.
BPAR Steroid resistant,36 months
|
1 Participants
|
2 Participants
|
|
Incidence of Biopsy Proven Antibody Mediated Rejection.
BPAR, T Cell depleting therapy 36 months
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: at 12 and 36 months post-transplantation.To evaluate the proportion of patients with chronic allograft nephropathy (interstitial fibrosis and tubular atrophy, IF/TA) by histopathology and its progression.The term chronic allograft nephropathy was used inappropriately in the protocol and therefore, replaced by interstitial fibrosis and tubular atrophy
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Chronic Allograft Nephropathy / Interstitial Fibrosis and Tubular Atrophy
12 months
|
3 Participants
|
3 Participants
|
|
Chronic Allograft Nephropathy / Interstitial Fibrosis and Tubular Atrophy
36 months
|
11 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: at 12 and 36 months post-transplantationPopulation: full analysis set 36 months analysis
The urinary protein/creatinine ratio will be descriptively summarized by treatment group at each visit. The incidence rate of patients with proteinuria will be categorized in \<0.2 g/mg/mg, 0.2\<2.0 mg/mg and ≥ 2.0 mg/mg and summarized by treatment groups at each visit.
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Baseline < 200mg/g
|
1 Participants
|
2 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Baseline 200 - < 2000 mg/g
|
12 Participants
|
12 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Baseline >= 2000 mg/g
|
14 Participants
|
15 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Month 12 < 200mg/g
|
19 Participants
|
28 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Month 12 200 - < 2000 mg/g
|
13 Participants
|
11 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Month 12 >= 2000 mg/g
|
0 Participants
|
0 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Month 36 < 200mg/g
|
23 Participants
|
23 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Month 36 200 - < 2000 mg/g
|
10 Participants
|
11 Participants
|
|
Proteinuria (Urinary Protein/Creatinine Ratio)
Month 36 >= 2000 mg/g
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: month 12 , month 36 post transplantation.Population: safety set, 36 months analysis
Evaluation of the potential effects upon the bone growth. The Z-score is a statistical tool which helps to assess data (here child growth parameters) relative to a reference or standard population. The Z-score describes the distance and direction of an observation away from the population median (or mean, however, here the median was used). A negative Z-score shows that data are lower than the median of the standard population, a positive Z-score shows that data are higher than the median of the standard population, and a Z-score of zero shows that the data are equal to the median of the standard population. The more the Z-score is distant from 0, the more expressed is for example underweight or overweight.
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Growth/Development : Weight, Height, BMI : Change From Baseline
Height month 12
|
0.37 z score
Standard Deviation 0.625
|
0.20 z score
Standard Deviation 0.537
|
|
Growth/Development : Weight, Height, BMI : Change From Baseline
Height month 36
|
0.72 z score
Standard Deviation 1.131
|
0.39 z score
Standard Deviation 0.776
|
|
Growth/Development : Weight, Height, BMI : Change From Baseline
Weight month 12
|
0.30 z score
Standard Deviation 0.732
|
0.42 z score
Standard Deviation 0.747
|
|
Growth/Development : Weight, Height, BMI : Change From Baseline
Weight month 36
|
0.61 z score
Standard Deviation 0.987
|
0.82 z score
Standard Deviation 1.268
|
|
Growth/Development : Weight, Height, BMI : Change From Baseline
BMI month 12
|
0.00 z score
Standard Deviation 0.716
|
0.24 z score
Standard Deviation 0.980
|
|
Growth/Development : Weight, Height, BMI : Change From Baseline
BMI month 36
|
0.02 z score
Standard Deviation 0.860
|
0.47 z score
Standard Deviation 1.231
|
SECONDARY outcome
Timeframe: baseline, 6 months, 12 months , 24 months, 36 monthsPopulation: full Analysis set 36 months
results given as eGFR values by time interval
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
Evaluation of Evolution of Renal Allograft Function Over Time
baseline
|
14.2 ml/min/1.73m2
Standard Deviation 11.38
|
13.1 ml/min/1.73m2
Standard Deviation 15.62
|
|
Evaluation of Evolution of Renal Allograft Function Over Time
month 6
|
76.6 ml/min/1.73m2
Standard Deviation 28.29
|
68.3 ml/min/1.73m2
Standard Deviation 21.02
|
|
Evaluation of Evolution of Renal Allograft Function Over Time
month 12
|
76.9 ml/min/1.73m2
Standard Deviation 21.61
|
67.8 ml/min/1.73m2
Standard Deviation 23.57
|
|
Evaluation of Evolution of Renal Allograft Function Over Time
month 24
|
72.9 ml/min/1.73m2
Standard Deviation 28.43
|
68.6 ml/min/1.73m2
Standard Deviation 23.26
|
|
Evaluation of Evolution of Renal Allograft Function Over Time
month 36
|
68.2 ml/min/1.73m2
Standard Deviation 21.60
|
69.6 ml/min/1.73m2
Standard Deviation 20.01
|
SECONDARY outcome
Timeframe: 12 months post-transplantationPopulation: Full Analysis set 12 months months
To evaluate renal function assessed by Glomerular Filtration Rate (eGFR) estimated by the Schwartz Formula (extended) (Schwartz, 2009). Results given as change from randomization
Outcome measures
| Measure |
EVR+rTAC
n=52 Participants
Investigational arm : Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
|
MMF+sTAC
n=54 Participants
Control arm : MMF continuation (in combination with tacrolimus and standard dose steroids)
|
|---|---|---|
|
To Evaluate Renal Function, Assessed by Glomerular Filtration Rate (eGFR) and Estimated by the Schwartz Formula (Extended), at Month 12
|
4.6 mL/min/1.73m2
Standard Deviation 11.94
|
-0.0 mL/min/1.73m2
Standard Deviation 23.92
|
Adverse Events
EVR+rTAC
Serious events: 0 serious events
Other events: 46 other events
Deaths: 0 deaths
MMF+sTAC
Serious events: 0 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
EVR+rTAC
n=52 participants at risk
EVR+rTAC
|
MMF+sTAC
n=54 participants at risk
MMF+sTAC
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
19.2%
10/52 • up to 36 months
AE additional description
|
20.4%
11/54 • up to 36 months
AE additional description
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.8%
2/52 • up to 36 months
AE additional description
|
18.5%
10/54 • up to 36 months
AE additional description
|
|
Blood and lymphatic system disorders
Polycythaemia
|
5.8%
3/52 • up to 36 months
AE additional description
|
0.00%
0/54 • up to 36 months
AE additional description
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
5.8%
3/52 • up to 36 months
AE additional description
|
0.00%
0/54 • up to 36 months
AE additional description
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.5%
6/52 • up to 36 months
AE additional description
|
11.1%
6/54 • up to 36 months
AE additional description
|
|
Ear and labyrinth disorders
Ear pain
|
9.6%
5/52 • up to 36 months
AE additional description
|
9.3%
5/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Abdominal pain
|
13.5%
7/52 • up to 36 months
AE additional description
|
11.1%
6/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.5%
6/52 • up to 36 months
AE additional description
|
9.3%
5/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Aphthous ulcer
|
17.3%
9/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Constipation
|
5.8%
3/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
13/52 • up to 36 months
AE additional description
|
29.6%
16/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.8%
3/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Nausea
|
7.7%
4/52 • up to 36 months
AE additional description
|
7.4%
4/54 • up to 36 months
AE additional description
|
|
Gastrointestinal disorders
Vomiting
|
19.2%
10/52 • up to 36 months
AE additional description
|
14.8%
8/54 • up to 36 months
AE additional description
|
|
General disorders
Fatigue
|
5.8%
3/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
General disorders
Pain
|
5.8%
3/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
General disorders
Pyrexia
|
26.9%
14/52 • up to 36 months
AE additional description
|
20.4%
11/54 • up to 36 months
AE additional description
|
|
Infections and infestations
BK virus infection
|
7.7%
4/52 • up to 36 months
AE additional description
|
14.8%
8/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Bronchitis
|
3.8%
2/52 • up to 36 months
AE additional description
|
7.4%
4/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Cystitis
|
5.8%
3/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Cytomegalovirus infection
|
5.8%
3/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Cytomegalovirus viraemia
|
0.00%
0/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Ear infection
|
1.9%
1/52 • up to 36 months
AE additional description
|
9.3%
5/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Epstein-Barr viraemia
|
5.8%
3/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Epstein-Barr virus infection
|
13.5%
7/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Gastroenteritis
|
7.7%
4/52 • up to 36 months
AE additional description
|
9.3%
5/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Influenza
|
5.8%
3/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Nasopharyngitis
|
30.8%
16/52 • up to 36 months
AE additional description
|
11.1%
6/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Oral herpes
|
3.8%
2/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Otitis media
|
7.7%
4/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Pharyngitis
|
11.5%
6/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Rhinitis
|
13.5%
7/52 • up to 36 months
AE additional description
|
9.3%
5/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Sinusitis
|
1.9%
1/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Tonsillitis
|
5.8%
3/52 • up to 36 months
AE additional description
|
14.8%
8/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Upper respiratory tract infection
|
15.4%
8/52 • up to 36 months
AE additional description
|
11.1%
6/54 • up to 36 months
AE additional description
|
|
Infections and infestations
Urinary tract infection
|
25.0%
13/52 • up to 36 months
AE additional description
|
27.8%
15/54 • up to 36 months
AE additional description
|
|
Investigations
Blood creatinine increased
|
5.8%
3/52 • up to 36 months
AE additional description
|
11.1%
6/54 • up to 36 months
AE additional description
|
|
Investigations
Hepatic enzyme increased
|
5.8%
3/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Investigations
Weight decreased
|
0.00%
0/52 • up to 36 months
AE additional description
|
9.3%
5/54 • up to 36 months
AE additional description
|
|
Investigations
Weight increased
|
9.6%
5/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Acidosis
|
1.9%
1/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
7.7%
4/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.8%
3/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/52 • up to 36 months
AE additional description
|
7.4%
4/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Iron deficiency
|
11.5%
6/52 • up to 36 months
AE additional description
|
0.00%
0/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
5.8%
3/52 • up to 36 months
AE additional description
|
0.00%
0/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Obesity
|
3.8%
2/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
5.8%
3/52 • up to 36 months
AE additional description
|
7.4%
4/54 • up to 36 months
AE additional description
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.7%
4/52 • up to 36 months
AE additional description
|
1.9%
1/54 • up to 36 months
AE additional description
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
1.9%
1/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Nervous system disorders
Headache
|
19.2%
10/52 • up to 36 months
AE additional description
|
20.4%
11/54 • up to 36 months
AE additional description
|
|
Nervous system disorders
Tremor
|
1.9%
1/52 • up to 36 months
AE additional description
|
7.4%
4/54 • up to 36 months
AE additional description
|
|
Renal and urinary disorders
Haematuria
|
5.8%
3/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Renal and urinary disorders
Proteinuria
|
7.7%
4/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.2%
11/52 • up to 36 months
AE additional description
|
18.5%
10/54 • up to 36 months
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.8%
3/52 • up to 36 months
AE additional description
|
5.6%
3/54 • up to 36 months
AE additional description
|
|
Skin and subcutaneous tissue disorders
Dermatitis diaper
|
5.8%
3/52 • up to 36 months
AE additional description
|
0.00%
0/54 • up to 36 months
AE additional description
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/52 • up to 36 months
AE additional description
|
7.4%
4/54 • up to 36 months
AE additional description
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.6%
5/52 • up to 36 months
AE additional description
|
3.7%
2/54 • up to 36 months
AE additional description
|
|
Vascular disorders
Hypertension
|
13.5%
7/52 • up to 36 months
AE additional description
|
11.1%
6/54 • up to 36 months
AE additional description
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER