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

Phase 4

Completed

• Conditions: Drug Interaction Potentiation
• Interventions: Drug: Everolimus; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Methylprednisolone; Drug: Prednisolone

• Registration Number: NCT02077556
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2014-03-02
• Study First Submitted QC: 2014-03-02
• Study First Posted: 2014-03-04
• Study Start: 2014-04
• Status Verified: 2018-07
• Primary Completion: 2019-01-15
• Study Completion: 2019-01-15
• Last Update Submitted: 2019-07-22
• Last Update Posted: 2019-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Everolimus	Everolimus	Everolimus/Tacrolimus/Methylprednisolone \& Prednisolone
Everolimus	Tacrolimus	Everolimus/Tacrolimus/Methylprednisolone \& Prednisolone
Everolimus	Prednisolone	Everolimus/Tacrolimus/Methylprednisolone \& Prednisolone
Mycophenolate mofetil	Mycophenolate mofetil	Mycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone
Mycophenolate mofetil	Tacrolimus	Mycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone
Mycophenolate mofetil	Prednisolone	Mycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone
Everolimus	Methylprednisolone	Everolimus/Tacrolimus/Methylprednisolone \& Prednisolone
Mycophenolate mofetil	Methylprednisolone	Mycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic profiles	Post-operation day 8-10	Pharmacokinetic parameters include the maximum concentration, trough concentration, area under the whole-blood concentration-time curve between 0 and 12 hours, time to maximum concentration, volume of distribution at steady state, and clearance at steady state.

Secondary Outcome Measures

Name	Time	Method
Acute rejection	Within the first 2 weeks post-transplantation

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan