Everolimus in Combination With Cyclosporine Microemulsion in de Novo Renal Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study was to allow the continuation of everolimus treatment in patients who have completed the core study (NCT00170885) and to collect long-term safety, tolerability, and efficacy data in a group of patients treated with the upper everolimus target levels plus very low dose cyclosporin in comparison with the standard everolimus target levels plus low dose cyclosporin in patients with renal transplantation.

Official Title
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An 18 Month Extension to the Multicenter, Randomized, Open-label Trial (NCT00170885) to Evaluate the Safety, Tolerability, and Efficacy of Two Regimens of Everolimus Plus Cyclosporine Microemulsion, Given According to Different Blood Target Levels, in de Novo Renal Transplant Recipients

Conditions
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Transplantation Infection

Intervention / Treatment
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* Drug: Everolimus 0.25 and 0.75 mg tablets
* Drug: Cyclosporine very low dose (150-300 ng/mL) microemulsion
* Drug: Cyclosporine low dose (350-500 ng/mL) microemulsion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with functioning graft who had completed the 6-month treatment period of core study Patients who were receiving treatment with either everolimus and cyclosporin at the end of the core study Patients who signed the informed consent of the present study extension Exclusion Criteria: - Women who were pregnant, lactating or who wished to became pregnant. Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upper everolimus blood target + very low dose cyclosporine<br>Patients received everolimus orally twice daily at a dose that was adjusted to achieve a drug blood trough level in the range of 8-12 ng/mL. Patients also received a very low dose of cyclosporine (150-300 ng/mL) orally twice daily that was adjusted to maintain a drug blood level of 200 ng/mL 2 hours after the morning dose. Both drugs were taken in the morning and again 12 hours later. The drugs were taken consistently either before, during, or after meals. No grapefruit or grapefruit juice was allowed throughout the study. | Drug: Everolimus 0.25 and 0.75 mg tablets<br>* The dose of everolimus for each patient was adjusted to achieve the target everolimus blood level range. Everolimus blood trough level was measured 5 days after any dose adjustment to verify that the blood level was within the desired target level range.<br>Drug: Cyclosporine very low dose (150-300 ng/mL) microemulsion<br>* The dose of cyclosporine for each patient was adjusted to achieve the target cyclosporine blood level. Cyclosporine dose adjustments were based on drug blood level determined from whole blood samples taken 2 hours (± 10 min) after the morning dose.<br>* Other names: Neoral;|
| Active Comparator: Standard everolimus blood target + low dose cyclosporine<br>Patients received everolimus orally twice daily at a dose that was adjusted to achieve a drug blood trough level in the range of 3-8 ng/mL. Patients also received a low dose of cyclosporine (350-500 ng/mL) orally twice daily that was adjusted to maintain a drug blood level of 400 ng/mL 2 hours after the morning dose. Both drugs were taken in the morning and again 12 hours later. The drugs were taken consistently either before, during, or after meals. No grapefruit or grapefruit juice was allowed throughout the study. | Drug: Everolimus 0.25 and 0.75 mg tablets<br>* The dose of everolimus for each patient was adjusted to achieve the target everolimus blood level range. Everolimus blood trough level was measured 5 days after any dose adjustment to verify that the blood level was within the desired target level range.<br>Drug: Cyclosporine low dose (350-500 ng/mL) microemulsion<br>* The dose of cyclosporine for each patient was adjusted to achieve the target cyclosporine blood level. Cyclosporine dose adjustments were based on drug blood level determined from whole blood samples taken 2 hours (± 10 min) after the morning dose.<br>* Other names: Neoral;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Biopsy-proven Acute Rejection | A graft core biopsy was performed on all suspected acute rejection episodes within 48 hours. Biopsies were read by the local pathologist according to the 1997 Banff criteria. A biopsy-proven acute rejection was be defined as a biopsy graded IA, IB, IIA, IIB, or III. | Baseline to end of study (Month 24) | 
| Renal Function Assessed by Creatinine Clearance | Renal function was assessed by measuring serum creatinine and by computing creatinine clearance using the formula of Cockcroft-Gault. | Month 12, Month 18, and Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Died, Number of Participants Who Lost Their Graft, and Number of Participants Who Died or Lost Their Graft | A participant lost his graft if he/she started dialysis and was not able to subsequently be removed from dialysis or underwent graft nephrectomy. | Baseline to end of study (Month 24) | 
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Deaths | Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. | Baseline to end of study (Month 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunosuppression, kidney transplantation, everolimus, safety