Kidney Transplantation
Conditions
Keywords
Renal transplantation, everolimus, mycophenolate mofetil, cyclosporine, corticosteroid, basiliximab, Banff diagnosis, Acute rejection, Therapeutic drug monitoring (TDM), de novo renal transplant recipient
Brief summary
The 12 Month Core Study (CRAD001A1202) was designed to evaluate the efficacy and safety comparing concentration-controlled everolimus (1.5 mg/day starting dose) with reduced dose cyclosporine and corticosteroids versus 2 g/day mycophenolate mofetil (MMF) with standard dose cyclosporine and corticosteroids in de novo renal transplant recipients. Extension Study (CRAD001A1202E1): Until 24 months after renal transplantation, the study was designed to evaluate the long-term safety and efficacy comparing concentration-controlled everolimus with reduced dose cyclosporine (Neoral®) and corticosteroids versus mycophenolate mofetil with standard dose Neoral® and corticosteroids in de novo renal transplant recipients. Beyond 24 months after renal transplantation, the study was designed to provide everolimus treatment for patients in everolimus group until everolimus is approved and marketed in Japan.
Interventions
DRUGEverolimus
0.75 mg twice daily, trough level adjusting between 3 and 8 ng/ml.
DRUGMycophenolate mofetil (MMF)
The initial dose of 2 gm/day Mycophenolate mofetil was started within 24-36 hours from reperfusion after transplantation. MMF was administered daily for 12 months in the core study and 12 months in the extension study.
DRUGBasiliximab
Patients received first dose of basiliximab (20 mg) 2 hours prior to transplantation and 20 mg at Day 4 or according to local practice
DRUGCyclosporine A
The cyclosporine was initiated either pre-transplant or within 24 hours after transplantation following local regime. Standard dose of cyclosporine was administered with MMF. The Reduced dose of cyclosporine was administered with everolimus.
DRUGCorticosteroid
Corticosteroid was administered according to local practice during the trial but at a dose not less than 5mg per day for 12 months of the study
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Core Study Inclusion Criteria: * Male or female de novo renal transplant recipients between 18 and 65 years of age * Patients who are receiving a primary cadaveric donor or non-human leukocyte antigen (non-HLA) identical living donor kidney transplant * Patients who have given written informed consent to participate in the study * Females capable of becoming pregnant must have a negative pregnancy test prior to randomization. Core Study
Exclusion criteria
* Patients with no evidence of graft function within 24 hours of transplantation are excluded * Recipients of dual kidney transplants * Patients who are recipients of multiple solid organ or tissue transplants, or have previously received an organ or tissue transplant. * Recipients of kidneys from HLA-identical living related donors * Patients who are recipients of ABO incompatible transplants or T cell cross match positive transplant. Although Panel Reactive Antibodies (PRA) test is not mandatory, patients whose most recent anti-HLA Class I PRA \>20% By a CDC-(Complement dependent cytotoxicity) based assay or \>50% by a Flow Cytometry or ELISA (Enzyme linked immunosorbent assay) -based assay * Patients who have tested positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or Hepatitis B surface antigen. Laboratory results obtained within 6 months prior to randomization are acceptable, otherwise these tests should be performed within two weeks prior to randomization. * Recipients of organs from donors who test positive for Hepatitis B surface antigen, HCV or HIV are excluded * Donor organ with a cold ischemia time \>24 hours * Donor age greater than 65 years * Patients with platelet count \<100,000/mm at baseline before transplantation * Patients with an absolute neutrophil count of \< 1,500/mm³ or white blood cell count of \< 4,500/mm³ at baseline before transplantation * Patients who have severe hypercholesterolemia (\>350 mg/dL; \>9 mmol/L) or hypertriglyceridemia (\>500 mg/dL; \>8.5 mmol/L). Patients with controlled hyperlipidemia are acceptable * Patients who have an abnormal liver profile such as alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase (ALP) or total bilirubin \>3 times the upper limit of normal (ULN) * Patients with a known hypersensitivity to either of the study drugs or their class, or to any of the excipients * Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 * Patients who are unable to take oral medication at time of randomization * Patients who received an investigational drug or who have been treated with a non-protocol immunosuppressive drug or treatment within 30 days or 5 half-lives prior to randomization * Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized excised non-melanomatous skin lesions * Patients with clinically significant systemic infection at time of transplant or within two weeks prior to transplant * Patients with a history of severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus * Patients who have cardiac failure at time of screening (resting dyspnea, with Grade ≥ 3 according to Old New York Heart Association Classification (Appendix 7) or any severe cardiac disease as determined by the investigator * Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study medication * Patients with abnormal physical or laboratory findings of clinical significance within 2 weeks prior to randomization which would interfere with the objectives of the study * Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation which would preclude renal biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed) * Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception. Extension Study Inclusion Criteria: * Patients who completed Month 12 visit in core study (including patients who had discontinued study medication) * Patients who had given written informed consent to participate in this extension study Extension Study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Number of Patients With Composite Efficacy Endpoint | 12 months | The composite efficacy endpoint consisted of treated biopsy proven acute rejection (BPAR) episodes, graft loss, death or 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. The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. For the individual components (including loss of follow-up)of the composite endpoint, patients are counted for the first event to occur. |
| Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula | Month 24 | Renal function was assessed by glomerular filtration rate (GFR) using the MDRD formula: GFR \[mL/min/1.73m2\] = 186.3\*(C-1.154)\*(A-0.203)\*G\*R C is the serum concentration of creatinine \[mg/dL\] A is age \[years\] G = 0.742 when gender is female, otherwise G=1 R = 1.21 when race is black, otherwise R=1 Loss to follow up (in In Primary Core Outcome Measure) is composite efficacy failure and contains incidence of treated BPAR, graft loss, death or loss to follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | 24 Months | Graft loss was defined as the day the patient started dialysis and was not able to subsequently be removed from dialysis or re-transplant. Loss-to-follow was a patient who did not experience a treated BPAR, graft loss or death and whose last day of contact was prior to Month 24. A Graft Biopsy was done within 48 hours of suspect rejection. Biopsies were read by the local pathologist according to the updated Banff '97 criteria. Treated BPAR was based on local laboratory biopsy results and was defined as a biopsy Banff criteria graded IA to III that was treated with anti-rejection therapy. |
| Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula | Month 24, Month 48 | The Nankivell formula was used to calculate GFR at Month 24: GFR\[mL/min\]=6.7/C + W/4 - UREA/2 - 100/H\^2 + 35 (25 for females) W= body weight \[kg\] H= height \[m\] C= serum creatinine \[mmol/L\] UREA= serum urea \[mmol\\L\] |
| Core Study: Number Participants With Combined Graft Loss, Death or Loss to Follow-up | 12 months | The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. A loss to follow-up in graft loss, death or loss to follow-up is a patient who did not experience graft loss or death and whose last day of contact was prior to Day 316, i.e. prior to the Month 12 visit window. |
| Extension Study: Everolimus Trough Levels | Month 24, Month 48 | Blood was collected at all visits after Day 3 for trough (collected 5 minutes before study drug dose) everolimus levels and was analyzed at a central laboratory using liquid chromatography mass spectrometry. |
| Extension Study: Cyclosporine Trough Levels | Month 24, Month 48 | Blood was collected at all visits after Day 3 for trough (collected 5 minutes before study drug dose) cyclosporine levels and was analyzed at a central laboratory using immunoassay. |
| Extension Study: Number of Participants With Adverse Events and Serious Adverse Events | 24 Months | Additional information about Adverse Events can be found in the Adverse Event Section. |
| Core Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula | Month 12 | Modification of Diet in Renal Disease (MDRD) formula is: Calculated GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where * C is the serum concentration of creatinine \[mg/dL\], * A is patient age at sample collection date \[years\], * G=0.742 when gender is female, otherwise G=1, * R=1.21 when race is black, otherwise R=1 |
Countries
Japan
Participant flow
Pre-assignment details
Core Study randomization was conducted within 24 hours post reperfusion. Participants who completed the 12 month visit of the Core Study and met inclusion/exclusion criteria were eligible to participate in the Extension Study and continued the same treatment as the Core Study until Month 24.
Participants by arm
| Arm | Count |
|---|---|
| Everolimus + Reduced Dose of Cyclosporine An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. | 61 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. | 61 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Study: 12 Months | Subject withdrew consent | 5 | 3 |
| Extension Study: After Month 24 | Subject withdrew consent | 2 | 0 |
| Extension Study: Month 12 to Month 24 | Did not receive study drug in Extension | 3 | 7 |
| Extension Study: Month 12 to Month 24 | Subject withdrew consent | 3 | 0 |
Baseline characteristics
| Characteristic | Everolimus + Reduced Dose of Cyclosporine | Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Total |
|---|---|---|---|
| Age Continuous | 42.5 years STANDARD_DEVIATION 14.13 | 38.6 years STANDARD_DEVIATION 11.36 | 40.5 years STANDARD_DEVIATION 12.92 |
| Sex: Female, Male Female | 15 Participants | 24 Participants | 39 Participants |
| Sex: Female, Male Male | 46 Participants | 37 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 61 | 61 / 61 |
| serious Total, serious adverse events | 37 / 61 | 37 / 61 |
Outcome results
Primary
Core Study: Number of Patients With Composite Efficacy Endpoint
The composite efficacy endpoint consisted of treated biopsy proven acute rejection (BPAR) episodes, graft loss, death or 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. The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. For the individual components (including loss of follow-up)of the composite endpoint, patients are counted for the first event to occur.
Time frame: 12 months
Population: The Intent-To-Treat (ITT) population consisted of all patients randomized after transplantation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Treated BPAR | 3 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Death | 0 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Graft Loss | 0 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Loss to follow up (see caveats) | 4 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Composite Efficacy Endpoint | 7 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Loss to follow up (see caveats) | 2 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Composite Efficacy Endpoint | 7 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Treated BPAR | 5 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Graft Loss | 0 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Number of Patients With Composite Efficacy Endpoint | Death | 0 Participants |
Primary
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula
Renal function was assessed by glomerular filtration rate (GFR) using the MDRD formula: GFR \[mL/min/1.73m2\] = 186.3\*(C-1.154)\*(A-0.203)\*G\*R C is the serum concentration of creatinine \[mg/dL\] A is age \[years\] G = 0.742 when gender is female, otherwise G=1 R = 1.21 when race is black, otherwise R=1
Time frame: Month 48
Population: Participants from the Extension Intent-to-treat population with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula | 59.80 mL/min/1.73m^2 |
Primary
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula
Renal function was assessed by glomerular filtration rate (GFR) using the MDRD formula: GFR \[mL/min/1.73m2\] = 186.3\*(C-1.154)\*(A-0.203)\*G\*R C is the serum concentration of creatinine \[mg/dL\] A is age \[years\] G = 0.742 when gender is female, otherwise G=1 R = 1.21 when race is black, otherwise R=1 Loss to follow up (in In Primary Core Outcome Measure) is composite efficacy failure and contains incidence of treated BPAR, graft loss, death or loss to follow-up
Time frame: Month 24
Population: Participants from the Extension Intent-to-treat population with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula | 58.90 mL/min/1.73m^2 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula | 54.95 mL/min/1.73m^2 |
Secondary
Core Study: Number Participants With Combined Graft Loss, Death or Loss to Follow-up
The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. A loss to follow-up in graft loss, death or loss to follow-up is a patient who did not experience graft loss or death and whose last day of contact was prior to Day 316, i.e. prior to the Month 12 visit window.
Time frame: 12 months
Population: The Intent-To-Treat (ITT) population consisted of all patients randomized after transplantation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Number Participants With Combined Graft Loss, Death or Loss to Follow-up | 5 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Number Participants With Combined Graft Loss, Death or Loss to Follow-up | 3 Participants |
Secondary
Core Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula
Modification of Diet in Renal Disease (MDRD) formula is: Calculated GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where * C is the serum concentration of creatinine \[mg/dL\], * A is patient age at sample collection date \[years\], * G=0.742 when gender is female, otherwise G=1, * R=1.21 when race is black, otherwise R=1
Time frame: Month 12
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Core Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula | 58.00 mL/min/1.73m^2 | Full Range 18.993 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Core Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula | 55.25 mL/min/1.73m^2 | Full Range 15.227 |
Secondary
Extension Study: Cyclosporine Trough Levels
Blood was collected at all visits after Day 3 for trough (collected 5 minutes before study drug dose) cyclosporine levels and was analyzed at a central laboratory using immunoassay.
Time frame: Month 24, Month 48
Population: Participants from the Extension safety population with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Cyclosporine Trough Levels | Month 24 | 54.1 ng/mL | Standard Deviation 39.07 |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Cyclosporine Trough Levels | Month 48 (n=7,0) | 34.2 ng/mL | Standard Deviation 37.94 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Cyclosporine Trough Levels | Month 24 | 105.5 ng/mL | Standard Deviation 44.16 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Cyclosporine Trough Levels | Month 48 (n=7,0) | NA ng/mL | — |
Secondary
Extension Study: Everolimus Trough Levels
Blood was collected at all visits after Day 3 for trough (collected 5 minutes before study drug dose) everolimus levels and was analyzed at a central laboratory using liquid chromatography mass spectrometry.
Time frame: Month 24, Month 48
Population: Participants from the Extension safety population with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Everolimus Trough Levels | Month 24 | 5.258 ng/mL | Standard Deviation 1.117 |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Everolimus Trough Levels | Month 48 (n=8) | 4.408 ng/mL | Standard Deviation 0.5986 |
Secondary
Extension Study: Number of Participants With Adverse Events and Serious Adverse Events
Additional information about Adverse Events can be found in the Adverse Event Section.
Time frame: 24 Months
Population: Participants from the Extension Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 50 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 30 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 50 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 30 Participants |
Secondary
Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR)
Graft loss was defined as the day the patient started dialysis and was not able to subsequently be removed from dialysis or re-transplant. Loss-to-follow was a patient who did not experience a treated BPAR, graft loss or death and whose last day of contact was prior to Month 24. A Graft Biopsy was done within 48 hours of suspect rejection. Biopsies were read by the local pathologist according to the updated Banff '97 criteria. Treated BPAR was based on local laboratory biopsy results and was defined as a biopsy Banff criteria graded IA to III that was treated with anti-rejection therapy.
Time frame: 24 Months
Population: Extension Intent-to-treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Treated BPAR | 3 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Death | 0 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Graft Loss | 0 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Loss to follow-up | 1 Participants |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Combined Efficacy Endpoint | 4 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Loss to follow-up | 0 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Combined Efficacy Endpoint | 5 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Treated BPAR | 5 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Graft Loss | 0 Participants |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) | Death | 0 Participants |
Secondary
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula
The Nankivell formula was used to calculate GFR at Month 24: GFR\[mL/min\]=6.7/C + W/4 - UREA/2 - 100/H\^2 + 35 (25 for females) W= body weight \[kg\] H= height \[m\] C= serum creatinine \[mmol/L\] UREA= serum urea \[mmol\\L\]
Time frame: Month 24, Month 48
Population: Participants from the Extension Intent-to-treat population with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula | Month 24 | 63.49 mL/min | Standard Deviation 20.479 |
| Everolimus + Reduced Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula | Month 48 (9,0) | 60.16 mL/min | Standard Deviation 9.892 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula | Month 24 | 59.24 mL/min | Standard Deviation 13.84 |
| Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine | Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula | Month 48 (9,0) | NA mL/min | — |