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

Drug Interaction Potentiation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02077556
• Other study ID #: 201312011MINA
• Status: Completed
• Phase: Phase 4
• Start date: April 2014
• Est. completion date: January 15, 2019

Study information

• Verified date: July 2018
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: January 15, 2019
• Est. primary completion date: January 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Interaction Potentiation

Intervention

Drug:
• Everolimus
Everolimus: 1 mg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 3-8 ng/mL
• 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)
• 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
• 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
• Prednisolone
Prednisolone: 20 mg orally once a day from post-operation day 8 to post-operation week 4, then titrated gradually

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic profiles	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.	Post-operation day 8-10
Secondary	Acute rejection		Within the first 2 weeks post-transplantation