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

Sponsor
National Taiwan University Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02077556
Collaborator
(none)
14
Enrollment
1
Location
2
Arms
57.5
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
14 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official 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
Study Start Date :
Apr 1, 2014
Actual Primary Completion Date :
Jan 15, 2019
Actual Study Completion Date :
Jan 15, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Everolimus

Everolimus/Tacrolimus/Methylprednisolone & Prednisolone

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

    • 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
    Other Names:
  • Prograf

    • 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
    Other Names:
  • Solu-Medrol

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

    		•
    Active Comparator: Mycophenolate mofetil

    Mycophenolate mofetil/Tacrolimus/ Methylprednisolone & Prednisolone

    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)
    Other Names:
  • CellCept

    • 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
    Other Names:
  • Prograf

    • 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
    Other Names:
  • Solu-Medrol

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Acute rejection [Within the first 2 weeks post-transplantation]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Taiwan University Hospital Taipei Taiwan

    Sponsors and Collaborators

    • National Taiwan University Hospital

    Investigators

    • Principal Investigator: Meng-Kun Tsai, National Taiwan University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Taiwan University Hospital
    ClinicalTrials.gov Identifier:
    NCT02077556
    Other Study ID Numbers:
    • 201312011MINA
    First Posted:
    Mar 4, 2014
    Last Update Posted:
    Jul 24, 2019
    Last Verified:
    Jul 1, 2018
    Keywords provided by National Taiwan University Hospital
    tacrolimus, everolimus, pharmacokinetics, drug interaction
    Additional relevant MeSH terms:
    Mycophenolic Acid
    Methylprednisolone
    Methylprednisolone Hemisuccinate
    Prednisolone
    Everolimus
    Tacrolimus

    Study Results

    No Results Posted as of Jul 24, 2019