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

Phase 3

Completed

• Conditions: Transplantation Infection
• Interventions: 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

• Registration Number: NCT01276457
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05
• Primary Completion: 2009-02
• Study Completion: 2009-02
• Study First Submitted: 2011-01-12
• Study First Submitted QC: 2011-01-12
• Study First Posted: 2011-01-13
• Results First Submitted: 2011-01-25
• Results First Submitted QC: 2011-03-22
• Results First Posted: 2011-04-19
• Status Verified: 2011-05
• Last Update Submitted: 2011-05-17
• Last Update Posted: 2011-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 223

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Upper everolimus blood target + very low dose cyclosporine	Cyclosporine very low dose (150-300 ng/mL) microemulsion	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.
Upper everolimus blood target + very low dose cyclosporine	Everolimus 0.25 and 0.75 mg tablets	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.
Standard everolimus blood target + low dose cyclosporine	Everolimus 0.25 and 0.75 mg tablets	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.
Standard everolimus blood target + low dose cyclosporine	Cyclosporine low dose (350-500 ng/mL) microemulsion	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.

Primary Outcome Measures

Name	Time	Method
Renal Function Assessed by Creatinine Clearance	Month 12, Month 18, and Month 24	Renal function was assessed by measuring serum creatinine and by computing creatinine clearance using the formula of Cockcroft-Gault.
Number of Participants With Biopsy-proven Acute Rejection	Baseline to end of study (Month 24)	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Died, Number of Participants Who Lost Their Graft, and Number of Participants Who Died or Lost Their Graft	Baseline to end of study (Month 24)	A participant lost his graft if he/she started dialysis and was not able to subsequently be removed from dialysis or underwent graft nephrectomy.
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Deaths	Baseline to end of study (Month 24)	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.