Effect of Everolimus on the Pharmacokinetics of Tacrolimus in Renal Transplant Patients

National Taiwan University

Status and phase: Completed; Phase 4

Conditions: Drug Interaction Potentiation

Treatments: Drug: Methylprednisolone; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Everolimus; Drug: Prednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT02077556

201312011MINA

Details and patient eligibility

About

The purpose of this study is to understand the effects of everolimus on tacrolimus pharmacokinetics (pk) in patients receiving de novo kidney transplants.

Full description

Multidrug immunosuppression regimens have synergistic effects which allow the use of lower doses of individual agents. These regimens generally include calcineurin inhibitors (CNIs: cyclosporine or tacrolimus), mammalian target of rapamycin (mTOR) inhibitors (everolimus or sirolimus), and corticosteroids. CNIs and mTOR inhibitors are substrates for cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp); in addition, cyclosporine is a inhibitor of CYP3A4 and P-gp. Therefore, concomitant administration of those drugs may alter their serum levels.

It is remained to be evaluated whether the pharmacokinetics or clinical efficacy of tacrolimus will be affected when the regimens contain everolimus in clinical practice and the effect of ABCB1、CYP3A4、CYP3A5、POR genetic polymorphism on the two Drugs. Mycophenolate mofetil (MMF) has no effect on pharmacokinetics of tacrolimus; therefore, MMF is used as a control to understand the effects of everolimus on pharmacokinetics of tacrolimus in patients receiving de novo kidney transplants. The effect of ABCB1、CYP3A4、CYP3A5、POR genetic polymorphism on the two Drugs was also assessed.

Enrollment: 14 patients

Sex: All

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• De novo kidney transplants
• 20 - 65 years old
• aspartate aminotransferase/alanine aminotransferase within 2 times the upper limit of normal range

Exclusion criteria

• Pregnancy
• Tuberculosis
• Hepatitis B or C carrier status
• Human immunodeficiency virus-positive status
• Retransplantation or multiorgan transplantation
• History of rheumatoid arthritis
• Use of drugs that might have enhanced or inhibited CYP3A4 or P-gp activity

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

Everolimus

Experimental group

Description:

Everolimus/Tacrolimus/Methylprednisolone \& Prednisolone

Treatment:

Drug: Prednisolone

Drug: Everolimus

Drug: Tacrolimus

Drug: Methylprednisolone

Mycophenolate mofetil

Active Comparator group

Description:

Mycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone

Treatment:

Drug: Prednisolone

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Drug: Methylprednisolone