Skip to main content
OpenTrials
Completed

NCT Number: NCT02077556

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

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Drug Interaction Potentiation

Age range

20 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

National Taiwan University Hospital

Taipei, Taiwan

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Everolimus

Drug

Everolimus: 1 mg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 3-8 ng/mL

Other names: Certican

Mycophenolate mofetil

Drug

Mycophenolate mofetil: 10-15 mg/kg orally every 12 hours from post-operation day 1 (decrease 50% dose if white blood cell < 4000/mcL)

Other names: CellCept

Tacrolimus

Drug

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

Other names: Prograf

methylprednisolone

Drug

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

Other names: Solu-Medrol

Prednisolone

Drug

Prednisolone: 20 mg orally once a day from post-operation day 8 to post-operation week 4, then titrated gradually

Other names: Predonine

Primary outcomes

  1. Pharmacokinetic profiles

    Time frame: 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 outcomes

  1. Acute rejection

    Time frame: Within the first 2 weeks post-transplantation

Sponsors and collaborators

Lead sponsor

National Taiwan University Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2019
Study completion
2019
First posted
Mar 4, 2014
Registry last updated
Jul 24, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.