NCT02077556

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

The Effect of Everolimus on the Pharmacokinetics of Tacrolimus in Renal Transplant Patients, and the Effect of ABCB1、CYP3A4、CYP3A5、PORGenetic Polymorphism on the Two Drugs

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 20 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Drug Interaction Potentiation

Interventions

Type	Name	Description
DRUG	Everolimus	Everolimus: 1 mg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 3-8 ng/mL
DRUG	Mycophenolate mofetil	Mycophenolate mofetil: 10-15 mg/kg orally every 12 hours from post-operation day 1 (decrease 50% dose if white blood cell \< 4000/mcL)
DRUG	Tacrolimus	Tacrolimus: 0.05-0.075 mg/kg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 8-12 ng/mL
DRUG	Methylprednisolone	Methylprednisolone: 50 mg iv every 6 hours on post-operation day 1, 40 mg iv every 6 hours on post-operation day 2, 30 mg iv every 6 hours on post-operation day 3, 20 mg iv every 6 hours on post-operation day 4, 20 mg iv every 8 hours on post-operation day 5, 20 mg iv every 12 hours on post-operation day 6, 20 mg iv on post-operation day 7
DRUG	Prednisolone	Prednisolone: 20 mg orally once a day from post-operation day 8 to post-operation week 4, then titrated gradually

Timeline

• Start date: 2014-04-01
• Primary completion: 2019-01-15
• Completion: 2019-01-15
• First posted: 2014-03-04
• Last updated: 2019-07-24

Locations

1 site across 1 country: Taiwan