Everolimus in Combination With Cyclosporine Microemulsion in de Novo Renal Transplant Recipients - Full Text View

Purpose

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.

Condition	Intervention	Phase
Transplantation Infection	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	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Sirolimus Cyclosporine Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Number of Participants With Biopsy-proven Acute Rejection [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
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.
Renal Function Assessed by Creatinine Clearance [ Time Frame: Month 12, Month 18, and Month 24 ] [ Designated as safety issue: No ]
Renal function was assessed by measuring serum creatinine and by computing creatinine clearance using the formula of Cockcroft-Gault.

Secondary Outcome Measures:

Number of Participants Who Died, Number of Participants Who Lost Their Graft, and Number of Participants Who Died or Lost Their Graft [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: Yes ]
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.

Enrollment:	223
Study Start Date:	May 2006
Study Completion Date:	February 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Upper everolimus blood target + very low dose cyclosporine 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 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. Drug: Cyclosporine very low dose (150-300 ng/mL) microemulsion 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. Other Name: Neoral
Active Comparator: Standard everolimus blood target + low dose cyclosporine 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 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. Drug: Cyclosporine low dose (350-500 ng/mL) microemulsion 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. Other Name: Neoral

Arms

Assigned Interventions

Experimental: Upper everolimus blood target + very low dose cyclosporine

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

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.

Drug: Cyclosporine very low dose (150-300 ng/mL) microemulsion

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.

Other Name: Neoral

Active Comparator: Standard everolimus blood target + low dose cyclosporine

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

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.

Drug: Cyclosporine low dose (350-500 ng/mL) microemulsion

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.

Other Name: Neoral

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01276457 History of Changes
Other Study ID Numbers:	CRAD001AIT02E1
Study First Received:	January 12, 2011
Results First Received:	January 25, 2011
Last Updated:	May 17, 2011
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Novartis:

immunosuppression
kidney transplantation
everolimus
safety

Additional relevant MeSH terms:

Cyclosporins
Cyclosporine
Everolimus
Sirolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors

Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 21, 2013

Everolimus in Combination With Cyclosporine Microemulsion in de Novo Renal Transplant Recipients (EVEREST)