Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02077556
Recruitment Status : Completed
First Posted : March 4, 2014
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Drug Interaction Potentiation Drug: Everolimus Drug: Mycophenolate mofetil Drug: Tacrolimus Drug: Methylprednisolone Drug: Prednisolone 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : April 2014
Actual Primary Completion Date : January 15, 2019
Actual Study Completion Date : January 15, 2019

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Predonine




Primary Outcome Measures :
  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 Outcome Measures :
  1. Acute rejection [ Time Frame: Within the first 2 weeks post-transplantation ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02077556


Locations
Layout table for location information
Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Meng-Kun Tsai National Taiwan University Hospital

Layout table for additonal information
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02077556    
Other Study ID Numbers: 201312011MINA
First Posted: March 4, 2014    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2018
Keywords provided by National Taiwan University Hospital:
tacrolimus, everolimus, pharmacokinetics, drug interaction
Additional relevant MeSH terms:
Layout table for MeSH terms
Sirolimus
Mycophenolic Acid
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Everolimus
Tacrolimus
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antiemetics