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

Novartis

Status and phase: Completed; Phase 3

Conditions: Transplantation Infection

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01276457

CRAD001AIT02E1

Details and patient eligibility

About

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.

Enrollment: 223 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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223 participants in 2 patient groups

Upper everolimus blood target + very low dose cyclosporine

Experimental group

Description:

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.

Treatment:

Drug: Everolimus 0.25 and 0.75 mg tablets

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

Standard everolimus blood target + low dose cyclosporine

Active Comparator group

Description:

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.

Treatment:

Drug: Everolimus 0.25 and 0.75 mg tablets

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