Kidney Transplant
Conditions
Keywords
Kidney transplant, renal transplant, immunosuppression, mycophenolate mofetil, tacrolimus, everolimus
Brief summary
The purpose of this phase 3b study is to compare the safety and efficacy of everolimus with low dose tacrolimus to mycophenolate mofetil with standard dose tacrolimus in kidney transplant recipients.
Interventions
Everolimus: * Dosage form: 0.75 mg, 0.25 mg, and 0.5 mg tablets * Dose: 1.5 mg per day * Frequency: 0.75 mg twice daily Tacrolimus: * Dose adjusted to maintain specific blood levels
DRUGmycophenolate mofetil and tacrolimus
Mycophenolate mofetil: - Dose form: 250 mg capsule - Dose: 2g per day - Frequency: 1g twice daily Tacrolimus: - Dose adjusted to maintain specific blood levels
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female renal recipients 18-70 years of age undergoing kidney transplantation, either primary or re-transplant; * Recipient of a cadaveric, deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death), living unrelated or non-HLA identical living related donor kidney; * Graft must be functional (producing greater than or equal to 100 ml of urine within 24 hours after transplantation) at time of randomization.
Exclusion criteria
* Donor organ with a cold ischemic time \> 30 hours; * Males or females who produce less than 100 ml of urine in the first 24 hours post-transplantation; * Males or females who are recipients of ABO incompatible transplants, or T cell, or B cell crossmatch positive transplant; * Males or females with severe total hypercholesterolemia or total hypertriglyceridemia (Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable); * Males or females who have any surgical or any medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might alter the absorption, distribution, metabolism and/or excretion of study medication. Other protocol related inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incidence of Composite Efficacy Failure | 12 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | 12 Months | Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus. |
| Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | 12 Months | Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK. |
| Estimated Glomerular Filtration Rate (eGFR) | 12 Months | 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 |
| Number of Participants With Incidence of Proteinuria Events | Baseline and 12 Months | Number of participants with Incidence of proteinuria events indicating chronic kidney disease |
| Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | 12 Months | Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class |
| Number of Participants With Incidence of New Onset of Diabetes Mellitus | 12 Months | 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) |
Countries
Canada, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 306 |
| 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. | 304 |
| Total | 610 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed Study | Death | 6 | 5 |
| Completed Study | Lost to Follow-up | 0 | 1 |
| Completed Study | Missing | 2 | 0 |
| Completed Study | Withdrawal by Subject | 8 | 16 |
| Completed Study Medication | Abnormal lab values | 0 | 2 |
| Completed Study Medication | Abnormal test procedure | 4 | 0 |
| Completed Study Medication | Administrative problems | 7 | 5 |
| Completed Study Medication | Adverse Event | 66 | 39 |
| Completed Study Medication | Death | 2 | 2 |
| Completed Study Medication | Graft loss | 2 | 5 |
| Completed Study Medication | Lost to Follow-up | 0 | 1 |
| Completed Study Medication | Protocol Deviation | 9 | 8 |
| Completed Study Medication | Subject no longer required study drug | 0 | 1 |
| Completed Study Medication | Unsatisfactory therapeutic effect | 7 | 0 |
| Completed Study Medication | Withdrawal by Subject | 8 | 9 |
Baseline characteristics
| Characteristic | Total | Everolimus and Low Dose Tacrolimus | Mycophenolate Mofetil and Standard Dose Tacrolimus |
|---|---|---|---|
| Age, Continuous | 49.2 Years STANDARD_DEVIATION 13.14 | 50.00 Years STANDARD_DEVIATION 13.34 | 48.4 Years STANDARD_DEVIATION 12.91 |
| BMI | 28.0 kg/m˄2 STANDARD_DEVIATION 5.35 | 27.7 kg/m˄2 STANDARD_DEVIATION 5.55 | 28.3 kg/m˄2 STANDARD_DEVIATION 5.13 |
| Diabetic status at randomization No | 404 Participants | 195 Participants | 209 Participants |
| Diabetic status at randomization Yes | 206 Participants | 111 Participants | 95 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 28 Participants | 17 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 144 Participants | 70 Participants | 74 Participants |
| Race/Ethnicity, Customized Caucasian | 397 Participants | 196 Participants | 201 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 33 Participants | 17 Participants | 16 Participants |
| Sex: Female, Male Female | 203 Participants | 101 Participants | 102 Participants |
| Sex: Female, Male Male | 407 Participants | 205 Participants | 202 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 302 / 306 | 299 / 304 |
| serious Total, serious adverse events | 154 / 306 | 142 / 304 |
Outcome results
Primary
Number of Participants With Incidence of Composite Efficacy Failure
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.
Time frame: 12 Months
Population: Full Analysis Set (FAS) consisted of all participants randomized after transplantation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Treated Biopsy-proven Acute rejection (BPAR) | 59 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Death | 6 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Graft Loss | 4 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Loss to follow up | 9 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Composite Endpoint | 76 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Loss to follow up | 17 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Composite Endpoint | 62 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Treated Biopsy-proven Acute rejection (BPAR) | 34 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Graft Loss | 12 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Composite Efficacy Failure | Death | 5 Participants |
Secondary
Estimated Glomerular Filtration Rate (eGFR)
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
Time frame: 12 Months
Population: Full Analysis Set (FAS) consisted of all patients randomized after transplantation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Estimated Glomerular Filtration Rate (eGFR) | 63.14 mL/min/1.73m˄2 | Standard Deviation 22.042 |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Estimated Glomerular Filtration Rate (eGFR) | 63.06 mL/min/1.73m˄2 | Standard Deviation 19.512 |
Secondary
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events
Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class
Time frame: 12 Months
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Investigations | 150 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Metabolism and nutrition disorders | 266 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Gastrointestinal disorders | 233 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Injury, poisoning and procedural complications | 223 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | General disorders &administration site conditions | 199 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Infections and infestations | 184 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Any system organ class | 303 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Renal and urinary disorders | 141 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Vascular disorders | 131 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Blood and lymphatic system disorders | 130 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Nervous system disorders | 125 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Respiratory, thoracic and mediastinal disorders | 122 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Musculoskeletal and connective tissue disorders | 110 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Skin and subcutaneous tissue disorders | 109 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Psychiatric disorders | 96 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Reproductive system and breast disorders | 56 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Cardiac disorders | 51 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Eye disorders | 26 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Immune system disorders | 13 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Endocrine disorders | 12 Participants |
| Everolimus and Low Dose Tacrolimus | 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 |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Ear and labyrinth disorders | 7 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Hepatobiliary disorders | 6 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Surgical and medical procedures | 2 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Congenital, familial and genetic disorders | 0 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Social circumstances | 0 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Endocrine disorders | 8 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Any system organ class | 302 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Skin and subcutaneous tissue disorders | 108 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Metabolism and nutrition disorders | 263 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Congenital, familial and genetic disorders | 6 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Gastrointestinal disorders | 247 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Psychiatric disorders | 106 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Injury, poisoning and procedural complications | 202 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Neoplasms benign,malignant,other incl cysts/polyps | 15 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | General disorders &administration site conditions | 177 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Reproductive system and breast disorders | 40 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Infections and infestations | 196 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Surgical and medical procedures | 0 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Investigations | 143 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Cardiac disorders | 47 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Renal and urinary disorders | 160 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Ear and labyrinth disorders | 11 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Vascular disorders | 121 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Eye disorders | 36 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Blood and lymphatic system disorders | 163 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Social circumstances | 1 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Nervous system disorders | 150 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Immune system disorders | 11 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Respiratory, thoracic and mediastinal disorders | 134 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Hepatobiliary disorders | 3 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events | Musculoskeletal and connective tissue disorders | 114 Participants |
Secondary
Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease)
Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.
Time frame: 12 Months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | CMV syndrome event | 9 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | Lab evidence of CMV Viremia | 7 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | CMV Disease | 2 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | CMV syndrome event | 13 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | Lab evidence of CMV Viremia | 10 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) | CMV Disease | 8 Participants |
Secondary
Number of Participants With Incidence of New Onset of Diabetes Mellitus
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)
Time frame: 12 Months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of New Onset of Diabetes Mellitus | Any New Onset Diabetes | 25 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of New Onset of Diabetes Mellitus | randomGlucose≥200mg/dL w/2 fastingGlucose≥126mg/dL | 15 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of New Onset of Diabetes Mellitus | Concomitant Diabetes medicine for 30 days or more | 13 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of New Onset of Diabetes Mellitus | Any New Onset Diabetes | 22 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of New Onset of Diabetes Mellitus | randomGlucose≥200mg/dL w/2 fastingGlucose≥126mg/dL | 12 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of New Onset of Diabetes Mellitus | Concomitant Diabetes medicine for 30 days or more | 14 Participants |
Secondary
Number of Participants With Incidence of Proteinuria Events
Number of participants with Incidence of proteinuria events indicating chronic kidney disease
Time frame: Baseline and 12 Months
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Proteinuria Events | Baseline: Proteinuria (>=300 mg/g) | 243 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence of Proteinuria Events | Month 12, Day 316-450: Proteinuria (>=300 mg/g) | 36 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Proteinuria Events | Baseline: Proteinuria (>=300 mg/g) | 250 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence of Proteinuria Events | Month 12, Day 316-450: Proteinuria (>=300 mg/g) | 35 Participants |
Secondary
Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy
Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK.
Time frame: 12 Months
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | Lab evidence of BKV Viremia | 19 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | Lab evidence of BKV Viruria | 19 Participants |
| Everolimus and Low Dose Tacrolimus | Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | BKV Disease (Nephropathy) | 5 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | Lab evidence of BKV Viremia | 27 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | Lab evidence of BKV Viruria | 15 Participants |
| Mycophenolate Mofetil and Standard Dose Tacrolimus | Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy | BKV Disease (Nephropathy) | 5 Participants |