Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients

Summary

The reason for this extension is to evaluate the long-term safety and efficacy of two concentration-controlled everolimus regimen in de novo liver transplant recipients. The most important long-term safety assessments include evaluation of renal function, progression of HCV related allograft fibrosis, and other treatment related effects at Month 36 post-transplantation compared to extension baseline (Months 24 post-transplantation).

Conditions

• Liver Transplant Recipient

Interventions

DRUG

Tacrolimus (reduced tacrolimus)

After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study.

DRUG

Everolimus (reduced tacrolimus)

Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL for the duration of the study.

DRUG

Tacrolimus (tacrolimus elimination)

After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization. Tacrolimus elimination was started beginning at Month 4. Tacrolimus was tapered after everolimus whole blood trough levels were within the target range of 6-10 ng/mL. Tacrolimus was completely eliminated by the end of Month 4.

DRUG

Everolimus (tacrolimus elimination)

Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL.

DRUG

Tacrolimus (tacrolimus control)

Tacrolimus trough levels were targeted to be maintained at 8-12 ng/mL until Month 4. At Month 4, tacrolimus whole blood trough levels were decreased to a target trough level of 6-10 ng/mL for the remainder of the study.

DRUG

Corticosteroids

For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids could be used for the duration of the study but could not be eliminated before Month 6. The corticosteroids were not specified in the protocol because they were adminsitered to the participants according to local practice as part of standard of care.

Sponsors & Collaborators

• Novartis Pharmaceuticals

  lead INDUSTRY

Principal Investigators

• Novartis Pharmaceuticals · Novartis Pharmaceuticals

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-03-31

Primary Completion

2013-05-03

Completion

2013-05-03

Countries

• United States
• Argentina
• Australia
• Belgium
• Brazil
• Colombia
• Czechia
• France
• Germany
• Ireland
• Italy
• Netherlands
• Russia
• Spain
• Sweden
• United Kingdom

Study Locations