Comparative FK506 Drug Levels of Once Daily Advagraf in First Nations and Caucasian Patients With Liver Transplants

• Status: Completed
• Trial end date: 2019-11-27
• Target enrollment: 0
• Participant gender: All

Summary

Background:

Previous studies have documented differences in the pharmacokinetics (PK) of a once daily FK506 formulation (Advagraf) based on patient ethnicity. These findings may be of particular relevance to the First Nations population who constitute a large and increasing segment of the liver transplant population in Canada.

Aim:

The purpose of the present study is to determine whether PK differences exist for Advagraf in First Nations compared to Caucasian liver transplant patients.

Objectives:

1. Document and compare PK determinations for Advagraf in First Nations and Caucasian patients with stable liver transplants.

2. Document and compare CYP3A gene expression profiles in the two ethnic populations.

Study Design:

• single-centre, open-label

• consecutive enrollment (N=8/group)

• self-identified adult First Nations and Caucasian ethnic cohorts

• 7 day steady state conversion (mg/mg/day) from twice to once daily FK506 formulation

• timed blood samples at 0, 1.5, 2, 4, 6, and 24 hours post medication

• PK determinations:concentration at zero time (C0), time to maximum concentration (Tmax),Area Under the Curve (AUC 0-24), apparent oral clearance (CLoral) and maximum concentration (Cmax)

Methods:

• whole blood FK506 levels will be measured by UPLC tandem mass spectroscopy

• CYP3A allele analyses will be performed by Dr. Richard Kim, University of Western Ontario

Relevance:

The results of this study will serve to determine whether present guidelines for conversion of twice to once daily FK506 formulations need be modified for First Nations liver transplant patients.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Manitoba
• Treatments: Tacrolimus

Criteria

Inclusion Criteria:

• First Nations or Caucasian subjects between the ages of 18 and 70 years.

• A minimum of 12 months from the transplant procedure.

• No acute rejection episode within the previous 3 months.

• No evidence of pre-transplant liver disease recurrence

• Stable Tacrolimus dosage during the previous 3 months.

Exclusion Criteria:

• Patients with absorption problems or unable to take oral medications.

• Patients who are on steroids

• Patients unable or unwilling to provide informed consent.