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

NCT01276457 | Completed Phase 3 Results

• 1 other identifier: CRAD001AIT02E1
• Study Type: interventional
• Target: 223
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Transplantation Infection

Keywords

immunosuppression; kidney transplantation; everolimus; safety

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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)

• Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Deaths

  Baseline to end of study (Month 24)

Study Arms (2)

Upper everolimus blood target + very low dose cyclosporine

EXPERIMENTAL

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

Standard everolimus blood target + low dose cyclosporine

ACTIVE COMPARATOR

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

Interventions

Everolimus 0.25 and 0.75 mg tablets DRUG

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.

Standard everolimus blood target + low dose cyclosporine; Upper everolimus blood target + very low dose cyclosporine

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

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.

Also known as: Neoral

Upper everolimus blood target + very low dose cyclosporine

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

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.

Also known as: Neoral

Standard everolimus blood target + low dose cyclosporine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- Women who were pregnant, lactating or who wished to became pregnant.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Interventions

Cyclosporine

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

862 778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: January 13, 2011
• Study Start: May 1, 2006
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: May 20, 2011
• Results First Posted: April 19, 2011

Record last verified: 2011-05