Trial Outcomes & Findings for Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients (NCT NCT01025817)
NCT ID: NCT01025817
Last Updated: 2015-11-11
Results Overview
Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)\*, (2) graft loss\*\*, (3) participant death or(4) loss to follow-up. \*A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. \*\*Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
613 participants
Primary outcome timeframe
12 Months
Results posted on
2015-11-11
Participant Flow
In total 738 participants were screened, and 613 were transplanted and randomized to treatment (n=309 to EVR+Low TAC dose and n=304 to MMF+Std TAC). EVR=Everolimus and low dose tacrolimus, and MMF=Mycophenolate mofetil and standard dose tacrolimus.
Participant milestones
| Measure |
Everolimus and Low Dose Tacrolimus
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Completed Study Medication
STARTED
|
309
|
304
|
|
Completed Study Medication
COMPLETED
|
204
|
232
|
|
Completed Study Medication
NOT COMPLETED
|
105
|
72
|
|
Completed Study
STARTED
|
309
|
304
|
|
Completed Study
COMPLETED
|
293
|
282
|
|
Completed Study
NOT COMPLETED
|
16
|
22
|
Reasons for withdrawal
| Measure |
Everolimus and Low Dose Tacrolimus
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Completed Study Medication
Adverse Event
|
66
|
39
|
|
Completed Study Medication
Protocol Deviation
|
9
|
8
|
|
Completed Study Medication
Withdrawal by Subject
|
8
|
9
|
|
Completed Study Medication
Administrative problems
|
7
|
5
|
|
Completed Study Medication
Unsatisfactory therapeutic effect
|
7
|
0
|
|
Completed Study Medication
Abnormal test procedure
|
4
|
0
|
|
Completed Study Medication
Graft loss
|
2
|
5
|
|
Completed Study Medication
Death
|
2
|
2
|
|
Completed Study Medication
Abnormal lab values
|
0
|
2
|
|
Completed Study Medication
Subject no longer required study drug
|
0
|
1
|
|
Completed Study Medication
Lost to Follow-up
|
0
|
1
|
|
Completed Study
Withdrawal by Subject
|
8
|
16
|
|
Completed Study
Death
|
6
|
5
|
|
Completed Study
Missing
|
2
|
0
|
|
Completed Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
Total
n=610 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.00 Years
STANDARD_DEVIATION 13.34 • n=5 Participants
|
48.4 Years
STANDARD_DEVIATION 12.91 • n=7 Participants
|
49.2 Years
STANDARD_DEVIATION 13.14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
101 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
203 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
205 Participants
n=5 Participants
|
202 Participants
n=7 Participants
|
407 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
17 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
70 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
196 Participants
n=5 Participants
|
201 Participants
n=7 Participants
|
397 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
BMI
|
27.7 kg/m˄2
STANDARD_DEVIATION 5.55 • n=5 Participants
|
28.3 kg/m˄2
STANDARD_DEVIATION 5.13 • n=7 Participants
|
28.0 kg/m˄2
STANDARD_DEVIATION 5.35 • n=5 Participants
|
|
Diabetic status at randomization
Yes
|
111 Participants
n=5 Participants
|
95 Participants
n=7 Participants
|
206 Participants
n=5 Participants
|
|
Diabetic status at randomization
No
|
195 Participants
n=5 Participants
|
209 Participants
n=7 Participants
|
404 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 MonthsPopulation: Full Analysis Set (FAS) consisted of all participants randomized after transplantation
Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)\*, (2) graft loss\*\*, (3) participant death or(4) loss to follow-up. \*A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. \*\*Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis.
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=309 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Number of Participants With Incidence of Composite Efficacy Failure
Composite Endpoint
|
76 Participants
|
62 Participants
|
|
Number of Participants With Incidence of Composite Efficacy Failure
Treated Biopsy-proven Acute rejection (BPAR)
|
59 Participants
|
34 Participants
|
|
Number of Participants With Incidence of Composite Efficacy Failure
Graft Loss
|
4 Participants
|
12 Participants
|
|
Number of Participants With Incidence of Composite Efficacy Failure
Death
|
6 Participants
|
5 Participants
|
|
Number of Participants With Incidence of Composite Efficacy Failure
Loss to follow up
|
9 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Full Analysis Set (FAS) consisted of all patients randomized after transplantation
Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR \[mL/min/1.73m˄2\] = 186.3\*(C˄-1.154)\*(A˄-0.203)\*G\*R. DEFINITIONS: C = serum concentration of creatinine \[mg/dL\]; A = age \[years\]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=309 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Estimated Glomerular Filtration Rate (eGFR)
|
63.14 mL/min/1.73m˄2
Standard Deviation 22.042
|
63.06 mL/min/1.73m˄2
Standard Deviation 19.512
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Safety Set (SS) consisted of all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. The statement that a patient had no adverse events constitutes a safety assessment. Those who received at least 1 dose of drug but had no post-treatment safety data of any kind are excluded from SS.
Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease)
CMV syndrome event
|
9 Participants
|
13 Participants
|
|
Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease)
Lab evidence of CMV Viremia
|
7 Participants
|
10 Participants
|
|
Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease)
CMV Disease
|
2 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Safety Set (SS) consisted of all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. The statement that a patient had no adverse events constitutes a safety assessment. Those who received at least 1 dose of drug but had no post-treatment safety data of any kind are excluded from SS
Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK.
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy
Lab evidence of BKV Viremia
|
19 Participants
|
27 Participants
|
|
Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy
Lab evidence of BKV Viruria
|
19 Participants
|
15 Participants
|
|
Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy
BKV Disease (Nephropathy)
|
5 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Safety Set (SS) consisted of all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. The statement that a patient had no adverse events constitutes a safety assessment. Those who received at least 1 dose of drug but had no post-treatment safety data of any kind are excluded from SS.
Incidence of new onset diabetes mellitus defined as non-diabetic patients before transplantation, who are receiving glucose lowering treatment for more than 30 days post-transplant, or with a random plasma glucose ≥200 mg dL (11.1 mmol/L) with 2 fasting plasma glucose values ≥126 mg/dL (7 mmol/L)
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Number of Participants With Incidence of New Onset of Diabetes Mellitus
Any New Onset Diabetes
|
25 Participants
|
22 Participants
|
|
Number of Participants With Incidence of New Onset of Diabetes Mellitus
randomGlucose≥200mg/dL w/2 fastingGlucose≥126mg/dL
|
15 Participants
|
12 Participants
|
|
Number of Participants With Incidence of New Onset of Diabetes Mellitus
Concomitant Diabetes medicine for 30 days or more
|
13 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: Baseline and 12 MonthsPopulation: Safety Set (SS) consisted of all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. The statement that a patient had no adverse events constitutes a safety assessment. Those who received at least 1 dose of drug but had no post-treatment safety data of any kind are excluded from SS
Number of participants with Incidence of proteinuria events indicating chronic kidney disease
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Number of Participants With Incidence of Proteinuria Events
Baseline: Proteinuria (>=300 mg/g)
|
243 Participants
|
250 Participants
|
|
Number of Participants With Incidence of Proteinuria Events
Month 12, Day 316-450: Proteinuria (>=300 mg/g)
|
36 Participants
|
35 Participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Safety Set (SS) consisted of all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. The statement that a patient had no adverse events constitutes a safety assessment. Those who received at least 1 dose of drug but had no post-treatment safety data of any kind are excluded from SS
Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class
Outcome measures
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 Participants
Everolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 Participants
MMF treatment arm: The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Any system organ class
|
303 Participants
|
302 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Metabolism and nutrition disorders
|
266 Participants
|
263 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Gastrointestinal disorders
|
233 Participants
|
247 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Injury, poisoning and procedural complications
|
223 Participants
|
202 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
General disorders &administration site conditions
|
199 Participants
|
177 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Infections and infestations
|
184 Participants
|
196 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Investigations
|
150 Participants
|
143 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Renal and urinary disorders
|
141 Participants
|
160 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Vascular disorders
|
131 Participants
|
121 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Blood and lymphatic system disorders
|
130 Participants
|
163 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Nervous system disorders
|
125 Participants
|
150 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Respiratory, thoracic and mediastinal disorders
|
122 Participants
|
134 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Musculoskeletal and connective tissue disorders
|
110 Participants
|
114 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Skin and subcutaneous tissue disorders
|
109 Participants
|
108 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Psychiatric disorders
|
96 Participants
|
106 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Reproductive system and breast disorders
|
56 Participants
|
40 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Cardiac disorders
|
51 Participants
|
47 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Eye disorders
|
26 Participants
|
36 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Immune system disorders
|
13 Participants
|
11 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Endocrine disorders
|
12 Participants
|
8 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Neoplasms benign,malignant,other incl cysts/polyps
|
10 Participants
|
15 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Ear and labyrinth disorders
|
7 Participants
|
11 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Hepatobiliary disorders
|
6 Participants
|
3 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Surgical and medical procedures
|
2 Participants
|
0 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Congenital, familial and genetic disorders
|
0 Participants
|
6 Participants
|
|
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Social circumstances
|
0 Participants
|
1 Participants
|
Adverse Events
Everolimus and Low Dose Tacrolimus
Serious events: 154 serious events
Other events: 302 other events
Deaths: 0 deaths
Mycophenolate Mofetil and Standard Dose Tacrolimus
Serious events: 142 serious events
Other events: 299 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 participants at risk
Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 participants at risk
The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.98%
3/306
|
1.3%
4/304
|
|
Blood and lymphatic system disorders
Bandaemia
|
0.00%
0/306
|
0.33%
1/304
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.65%
2/306
|
0.33%
1/304
|
|
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
|
0.65%
2/306
|
0.33%
1/304
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.33%
1/306
|
0.33%
1/304
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/306
|
0.99%
3/304
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/306
|
0.33%
1/304
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.65%
2/306
|
0.00%
0/304
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
0.33%
1/306
|
0.00%
0/304
|
|
Cardiac disorders
Acute myocardial infarction
|
0.65%
2/306
|
1.3%
4/304
|
|
Cardiac disorders
Atrial fibrillation
|
0.65%
2/306
|
0.99%
3/304
|
|
Cardiac disorders
Bradycardia
|
0.33%
1/306
|
0.00%
0/304
|
|
Cardiac disorders
Cardiac arrest
|
0.33%
1/306
|
0.66%
2/304
|
|
Cardiac disorders
Cardiac failure congestive
|
1.6%
5/306
|
0.00%
0/304
|
|
Cardiac disorders
Cardiogenic shock
|
0.00%
0/306
|
0.33%
1/304
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/306
|
0.33%
1/304
|
|
Cardiac disorders
Myocardial infarction
|
0.65%
2/306
|
0.66%
2/304
|
|
Cardiac disorders
Sinus tachycardia
|
0.33%
1/306
|
0.00%
0/304
|
|
Congenital, familial and genetic disorders
Congenital cystic kidney disease
|
0.00%
0/306
|
0.33%
1/304
|
|
Congenital, familial and genetic disorders
Congenital renal cyst
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Abdominal distension
|
0.65%
2/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Abdominal pain
|
0.65%
2/306
|
0.66%
2/304
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.33%
1/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/306
|
0.66%
2/304
|
|
Gastrointestinal disorders
Constipation
|
0.33%
1/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Diabetic gastroparesis
|
0.65%
2/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Diarrhoea
|
2.3%
7/306
|
2.6%
8/304
|
|
Gastrointestinal disorders
Erosive oesophagitis
|
0.33%
1/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Gastritis
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Ileus
|
0.33%
1/306
|
0.66%
2/304
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.33%
1/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Internal hernia
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Localised intraabdominal fluid collection
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Nausea
|
2.3%
7/306
|
1.3%
4/304
|
|
Gastrointestinal disorders
Neutropenic colitis
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Oral pain
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Pancreatitis
|
0.65%
2/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Peptic ulcer
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Retroperitoneal haematoma
|
0.33%
1/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.65%
2/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Tongue ulceration
|
0.33%
1/306
|
0.00%
0/304
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/306
|
0.33%
1/304
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
8/306
|
2.3%
7/304
|
|
General disorders
Asthenia
|
0.33%
1/306
|
0.00%
0/304
|
|
General disorders
Chest pain
|
0.65%
2/306
|
1.6%
5/304
|
|
General disorders
Chills
|
0.33%
1/306
|
0.33%
1/304
|
|
General disorders
Device malfunction
|
0.33%
1/306
|
0.33%
1/304
|
|
General disorders
Fatigue
|
0.33%
1/306
|
0.00%
0/304
|
|
General disorders
General physical health deterioration
|
0.00%
0/306
|
0.33%
1/304
|
|
General disorders
Generalised oedema
|
0.33%
1/306
|
0.33%
1/304
|
|
General disorders
Hernia
|
0.65%
2/306
|
0.33%
1/304
|
|
General disorders
Impaired healing
|
0.98%
3/306
|
0.00%
0/304
|
|
General disorders
Irritability
|
0.00%
0/306
|
0.33%
1/304
|
|
General disorders
Medical device complication
|
0.00%
0/306
|
0.33%
1/304
|
|
General disorders
Oedema
|
0.65%
2/306
|
0.00%
0/304
|
|
General disorders
Oedema peripheral
|
0.98%
3/306
|
0.66%
2/304
|
|
General disorders
Pyrexia
|
4.2%
13/306
|
3.6%
11/304
|
|
General disorders
Rebound effect
|
0.00%
0/306
|
0.33%
1/304
|
|
General disorders
Sluggishness
|
0.00%
0/306
|
0.33%
1/304
|
|
Immune system disorders
Kidney transplant rejection
|
0.33%
1/306
|
0.33%
1/304
|
|
Immune system disorders
Transplant rejection
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Adenovirus infection
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
BK virus infection
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Bacteraemia
|
0.33%
1/306
|
1.3%
4/304
|
|
Infections and infestations
Bacterial pyelonephritis
|
0.00%
0/306
|
0.66%
2/304
|
|
Infections and infestations
Bronchitis
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Cellulitis
|
2.0%
6/306
|
0.99%
3/304
|
|
Infections and infestations
Cellulitis of male external genital organ
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Cerebral fungal infection
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Clostridial infection
|
0.98%
3/306
|
0.99%
3/304
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/306
|
0.66%
2/304
|
|
Infections and infestations
Cystitis
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/306
|
1.6%
5/304
|
|
Infections and infestations
Cytomegalovirus viraemia
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Device related infection
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Enterococcal bacteraemia
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Escherichia bacteraemia
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Escherichia sepsis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.65%
2/306
|
0.00%
0/304
|
|
Infections and infestations
Gangrene
|
0.65%
2/306
|
0.66%
2/304
|
|
Infections and infestations
Gastroenteritis
|
0.98%
3/306
|
0.66%
2/304
|
|
Infections and infestations
Gastroenteritis clostridial
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Gastroenteritis salmonella
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Gastroenteritis viral
|
0.98%
3/306
|
0.99%
3/304
|
|
Infections and infestations
Incision site infection
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Infection
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Influenza
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Lung infection pseudomonal
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Mastitis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Meningitis cryptococcal
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Metapneumovirus infection
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Oral herpes
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Osteomyelitis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Peritonitis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Pneumonia
|
4.2%
13/306
|
2.3%
7/304
|
|
Infections and infestations
Pneumonia bacterial
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Pneumonia cryptococcal
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Pneumonia cytomegaloviral
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Polyomavirus-associated nephropathy
|
0.00%
0/306
|
0.66%
2/304
|
|
Infections and infestations
Post procedural cellulitis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Pseudomonal bacteraemia
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Pulmonary mycosis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Pyelonephritis
|
2.0%
6/306
|
1.3%
4/304
|
|
Infections and infestations
Sepsis
|
0.33%
1/306
|
0.66%
2/304
|
|
Infections and infestations
Septic shock
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Sinusitis
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Staphylococcal infection
|
0.65%
2/306
|
0.33%
1/304
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Urinary tract infection
|
7.2%
22/306
|
7.9%
24/304
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.33%
1/306
|
0.66%
2/304
|
|
Infections and infestations
Urinary tract infection enterococcal
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Urinary tract infection pseudomonal
|
0.00%
0/306
|
0.33%
1/304
|
|
Infections and infestations
Urinary tract infection staphylococcal
|
0.33%
1/306
|
0.00%
0/304
|
|
Infections and infestations
Urosepsis
|
1.6%
5/306
|
2.3%
7/304
|
|
Infections and infestations
Viraemia
|
0.00%
0/306
|
0.66%
2/304
|
|
Infections and infestations
Viral infection
|
0.33%
1/306
|
0.33%
1/304
|
|
Infections and infestations
Wound infection
|
1.3%
4/306
|
0.66%
2/304
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Complications of transplant surgery
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Complications of transplanted kidney
|
1.3%
4/306
|
1.3%
4/304
|
|
Injury, poisoning and procedural complications
Device dislocation
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Graft complication
|
0.65%
2/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Graft dysfunction
|
2.9%
9/306
|
2.6%
8/304
|
|
Injury, poisoning and procedural complications
Graft loss
|
0.65%
2/306
|
0.99%
3/304
|
|
Injury, poisoning and procedural complications
Graft thrombosis
|
0.65%
2/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Incision site complication
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.65%
2/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Incisional hernia, obstructive
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Medical device complication
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Perinephric collection
|
0.98%
3/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Perirenal haematoma
|
0.98%
3/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Post procedural discharge
|
0.33%
1/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Post procedural myocardial infarction
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Post procedural urine leak
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Renal haematoma
|
0.00%
0/306
|
0.33%
1/304
|
|
Injury, poisoning and procedural complications
Seroma
|
0.65%
2/306
|
0.66%
2/304
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/306
|
0.66%
2/304
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Urinary anastomotic leak
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Vascular graft complication
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.33%
1/306
|
0.00%
0/304
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.98%
3/306
|
0.33%
1/304
|
|
Investigations
Blood creatine increased
|
0.33%
1/306
|
0.00%
0/304
|
|
Investigations
Blood creatinine increased
|
3.3%
10/306
|
4.6%
14/304
|
|
Investigations
Blood glucose increased
|
0.00%
0/306
|
0.33%
1/304
|
|
Investigations
Electrocardiogram ST segment elevation
|
0.33%
1/306
|
0.00%
0/304
|
|
Investigations
Escherichia test positive
|
0.33%
1/306
|
0.00%
0/304
|
|
Investigations
Transaminases increased
|
0.65%
2/306
|
0.00%
0/304
|
|
Investigations
Urine output decreased
|
0.33%
1/306
|
0.66%
2/304
|
|
Investigations
White blood cell count increased
|
0.00%
0/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.33%
1/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
6/306
|
1.6%
5/304
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.65%
2/306
|
2.3%
7/304
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.33%
1/306
|
0.66%
2/304
|
|
Metabolism and nutrition disorders
Fluid overload
|
2.0%
6/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.33%
1/306
|
0.00%
0/304
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.33%
1/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.65%
2/306
|
2.0%
6/304
|
|
Metabolism and nutrition disorders
Hyperglycaemic hyperosmolar nonketotic syndrome
|
0.00%
0/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.98%
3/306
|
2.0%
6/304
|
|
Metabolism and nutrition disorders
Hyperosmolar state
|
0.33%
1/306
|
0.00%
0/304
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.33%
1/306
|
0.00%
0/304
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/306
|
0.66%
2/304
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.33%
1/306
|
0.99%
3/304
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.33%
1/306
|
0.00%
0/304
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.33%
1/306
|
0.33%
1/304
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.33%
1/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.33%
1/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.00%
0/306
|
0.33%
1/304
|
|
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
|
0.00%
0/306
|
0.33%
1/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone giant cell tumour benign
|
0.33%
1/306
|
0.00%
0/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.00%
0/306
|
0.33%
1/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleural mesothelioma
|
0.00%
0/306
|
0.33%
1/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/306
|
0.33%
1/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.33%
1/306
|
0.00%
0/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal haemangioma
|
0.33%
1/306
|
0.00%
0/304
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Embolic stroke
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Headache
|
0.33%
1/306
|
0.33%
1/304
|
|
Nervous system disorders
Hypoxic-ischaemic encephalopathy
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Neuropathy peripheral
|
0.33%
1/306
|
0.00%
0/304
|
|
Nervous system disorders
Syncope
|
0.33%
1/306
|
0.00%
0/304
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Tremor
|
0.00%
0/306
|
0.33%
1/304
|
|
Nervous system disorders
Unresponsive to stimuli
|
0.00%
0/306
|
0.33%
1/304
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/306
|
0.33%
1/304
|
|
Psychiatric disorders
Confusional state
|
0.33%
1/306
|
0.33%
1/304
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/306
|
0.33%
1/304
|
|
Psychiatric disorders
Mental status changes
|
0.98%
3/306
|
0.99%
3/304
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Bladder spasm
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Calculus ureteric
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Cystitis haemorrhagic
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Focal segmental glomerulosclerosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Haematuria
|
0.65%
2/306
|
1.6%
5/304
|
|
Renal and urinary disorders
Hydronephrosis
|
0.98%
3/306
|
2.0%
6/304
|
|
Renal and urinary disorders
Hydroureter
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.65%
2/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Pelvi-ureteric obstruction
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Proteinuria
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Renal aneurysm
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Renal artery stenosis
|
0.65%
2/306
|
0.66%
2/304
|
|
Renal and urinary disorders
Renal artery thrombosis
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Renal cyst
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Renal cyst ruptured
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Renal failure
|
0.65%
2/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Renal failure acute
|
2.3%
7/306
|
5.3%
16/304
|
|
Renal and urinary disorders
Renal failure chronic
|
0.33%
1/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Renal impairment
|
0.98%
3/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Renal injury
|
0.33%
1/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Renal pain
|
0.00%
0/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Renal tubular necrosis
|
1.3%
4/306
|
0.66%
2/304
|
|
Renal and urinary disorders
Renal vein thrombosis
|
0.33%
1/306
|
0.66%
2/304
|
|
Renal and urinary disorders
Ureteric stenosis
|
0.65%
2/306
|
0.99%
3/304
|
|
Renal and urinary disorders
Urethral stenosis
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Urinary bladder haemorrhage
|
0.33%
1/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Urinary incontinence
|
0.33%
1/306
|
1.3%
4/304
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/306
|
0.99%
3/304
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.33%
1/306
|
0.33%
1/304
|
|
Renal and urinary disorders
Urinoma
|
0.65%
2/306
|
0.00%
0/304
|
|
Renal and urinary disorders
Vesicoureteric reflux
|
0.00%
0/306
|
0.33%
1/304
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.33%
1/306
|
0.00%
0/304
|
|
Reproductive system and breast disorders
Pelvic haematoma
|
0.33%
1/306
|
0.00%
0/304
|
|
Reproductive system and breast disorders
Prostatitis
|
0.33%
1/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/306
|
0.33%
1/304
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/306
|
0.33%
1/304
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.33%
1/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
5/306
|
2.0%
6/304
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.98%
3/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.33%
1/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.00%
0/306
|
0.33%
1/304
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.33%
1/306
|
0.66%
2/304
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.33%
1/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.65%
2/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.6%
5/306
|
0.33%
1/304
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/306
|
0.33%
1/304
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
2.3%
7/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary toxicity
|
0.33%
1/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.33%
1/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.98%
3/306
|
0.00%
0/304
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.6%
5/306
|
0.33%
1/304
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.33%
1/306
|
0.00%
0/304
|
|
Skin and subcutaneous tissue disorders
Diabetic foot
|
0.65%
2/306
|
0.00%
0/304
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.33%
1/306
|
0.00%
0/304
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.33%
1/306
|
0.00%
0/304
|
|
Surgical and medical procedures
Pyelotomy
|
0.33%
1/306
|
0.00%
0/304
|
|
Vascular disorders
Arteriovenous fistula
|
0.33%
1/306
|
0.33%
1/304
|
|
Vascular disorders
Blood pressure inadequately controlled
|
0.33%
1/306
|
0.00%
0/304
|
|
Vascular disorders
Deep vein thrombosis
|
1.3%
4/306
|
1.6%
5/304
|
|
Vascular disorders
Extremity necrosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Vascular disorders
Extrinsic iliac vein compression
|
0.33%
1/306
|
0.00%
0/304
|
|
Vascular disorders
Haematoma
|
0.33%
1/306
|
0.33%
1/304
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/306
|
0.33%
1/304
|
|
Vascular disorders
Hypertension
|
2.3%
7/306
|
0.99%
3/304
|
|
Vascular disorders
Hypertensive crisis
|
0.65%
2/306
|
0.00%
0/304
|
|
Vascular disorders
Hypotension
|
0.00%
0/306
|
0.99%
3/304
|
|
Vascular disorders
Iliac artery thrombosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Vascular disorders
Jugular vein thrombosis
|
0.65%
2/306
|
0.00%
0/304
|
|
Vascular disorders
Lymphocele
|
2.3%
7/306
|
1.3%
4/304
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/306
|
0.66%
2/304
|
|
Vascular disorders
Peripheral vascular disorder
|
0.33%
1/306
|
0.00%
0/304
|
|
Vascular disorders
Superior vena cava syndrome
|
0.33%
1/306
|
0.00%
0/304
|
|
Vascular disorders
Thrombophlebitis
|
0.65%
2/306
|
0.00%
0/304
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.00%
0/306
|
0.33%
1/304
|
|
Vascular disorders
Thrombosis
|
0.00%
0/306
|
0.33%
1/304
|
|
Vascular disorders
Venous stenosis
|
0.00%
0/306
|
0.66%
2/304
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/306
|
0.33%
1/304
|
Other adverse events
| Measure |
Everolimus and Low Dose Tacrolimus
n=306 participants at risk
Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
|
Mycophenolate Mofetil and Standard Dose Tacrolimus
n=304 participants at risk
The MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and a decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. The tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, the target level of tacrolimus was reduced to 5 - 8 ng/mL.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
27.1%
83/306
|
22.0%
67/304
|
|
Blood and lymphatic system disorders
Leukocytosis
|
7.2%
22/306
|
10.2%
31/304
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.8%
27/306
|
21.4%
65/304
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.3%
7/306
|
7.9%
24/304
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.2%
22/306
|
5.3%
16/304
|
|
Cardiac disorders
Tachycardia
|
7.2%
22/306
|
6.6%
20/304
|
|
Gastrointestinal disorders
Abdominal distension
|
5.6%
17/306
|
7.2%
22/304
|
|
Gastrointestinal disorders
Abdominal pain
|
9.5%
29/306
|
11.5%
35/304
|
|
Gastrointestinal disorders
Constipation
|
38.9%
119/306
|
39.5%
120/304
|
|
Gastrointestinal disorders
Diarrhoea
|
24.2%
74/306
|
40.1%
122/304
|
|
Gastrointestinal disorders
Dyspepsia
|
6.5%
20/306
|
7.6%
23/304
|
|
Gastrointestinal disorders
Flatulence
|
3.3%
10/306
|
6.2%
19/304
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.9%
18/306
|
9.2%
28/304
|
|
Gastrointestinal disorders
Nausea
|
36.3%
111/306
|
44.1%
134/304
|
|
Gastrointestinal disorders
Vomiting
|
14.7%
45/306
|
21.1%
64/304
|
|
General disorders
Fatigue
|
19.0%
58/306
|
17.1%
52/304
|
|
General disorders
Oedema
|
10.5%
32/306
|
9.2%
28/304
|
|
General disorders
Oedema peripheral
|
36.9%
113/306
|
28.9%
88/304
|
|
General disorders
Pyrexia
|
13.4%
41/306
|
15.5%
47/304
|
|
Infections and infestations
BK virus infection
|
10.5%
32/306
|
13.5%
41/304
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
13/306
|
6.6%
20/304
|
|
Infections and infestations
Upper respiratory tract infection
|
9.2%
28/306
|
10.9%
33/304
|
|
Infections and infestations
Urinary tract infection
|
16.0%
49/306
|
22.4%
68/304
|
|
Injury, poisoning and procedural complications
Graft dysfunction
|
11.4%
35/306
|
10.5%
32/304
|
|
Injury, poisoning and procedural complications
Incision site pain
|
15.0%
46/306
|
17.8%
54/304
|
|
Injury, poisoning and procedural complications
Procedural pain
|
30.4%
93/306
|
30.9%
94/304
|
|
Investigations
Blood creatinine increased
|
16.0%
49/306
|
13.5%
41/304
|
|
Investigations
Weight increased
|
6.5%
20/306
|
4.6%
14/304
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.0%
6/306
|
7.6%
23/304
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
17/306
|
5.9%
18/304
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
10.5%
32/306
|
9.9%
30/304
|
|
Metabolism and nutrition disorders
Fluid overload
|
6.9%
21/306
|
7.6%
23/304
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
3.9%
12/306
|
5.6%
17/304
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
24.5%
75/306
|
26.6%
81/304
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
30.4%
93/306
|
26.6%
81/304
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
23.2%
71/306
|
10.2%
31/304
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
7.5%
23/306
|
8.2%
25/304
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
15.0%
46/306
|
13.2%
40/304
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
6.5%
20/306
|
7.6%
23/304
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
18.3%
56/306
|
17.8%
54/304
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
33.3%
102/306
|
40.8%
124/304
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.6%
11/306
|
6.9%
21/304
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
35.3%
108/306
|
30.9%
94/304
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
11.4%
35/306
|
12.8%
39/304
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
6.9%
21/306
|
8.2%
25/304
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.1%
31/306
|
7.6%
23/304
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.9%
21/306
|
7.6%
23/304
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
4.9%
15/306
|
6.6%
20/304
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.2%
28/306
|
7.9%
24/304
|
|
Nervous system disorders
Dizziness
|
8.5%
26/306
|
11.8%
36/304
|
|
Nervous system disorders
Headache
|
14.4%
44/306
|
17.4%
53/304
|
|
Nervous system disorders
Hypoaesthesia
|
5.6%
17/306
|
3.0%
9/304
|
|
Nervous system disorders
Tremor
|
16.7%
51/306
|
28.3%
86/304
|
|
Psychiatric disorders
Anxiety
|
5.6%
17/306
|
10.9%
33/304
|
|
Psychiatric disorders
Insomnia
|
22.2%
68/306
|
23.4%
71/304
|
|
Renal and urinary disorders
Dysuria
|
7.8%
24/306
|
8.2%
25/304
|
|
Renal and urinary disorders
Haematuria
|
9.8%
30/306
|
10.9%
33/304
|
|
Renal and urinary disorders
Proteinuria
|
10.1%
31/306
|
6.2%
19/304
|
|
Renal and urinary disorders
Renal tubular necrosis
|
6.5%
20/306
|
6.2%
19/304
|
|
Renal and urinary disorders
Urinary retention
|
5.6%
17/306
|
4.3%
13/304
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.2%
28/306
|
14.1%
43/304
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.1%
40/306
|
16.1%
49/304
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.5%
23/306
|
7.9%
24/304
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.5%
20/306
|
2.3%
7/304
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.0%
6/306
|
5.9%
18/304
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.5%
32/306
|
10.5%
32/304
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.8%
24/306
|
3.9%
12/304
|
|
Vascular disorders
Hypertension
|
20.9%
64/306
|
23.4%
71/304
|
|
Vascular disorders
Hypotension
|
8.2%
25/306
|
9.5%
29/304
|
Additional Information
Study Director
Novartis
Phone: +1 (862) 778-8300
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 (i.e., data from all sites) in the clinical trial; or disclosure of the trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER