Prograf-Advagraf Cross Over Conversion Study

NCT ID: NCT01797341

Last Updated: 2014-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2014-02-28

Brief Summary

The present study is aimed at evaluating the impact of a switch from Prograf to Advagraf on renal function, trough tacrolimus levels, drug-related adverse effects and adherence in stable recipients of kidney-pancreas transplants. MPA pharmacokinetics will also be evaluated. The results of this study have the potential to change current practice.

Detailed Description

Tacrolimus (Prograf ©) has become part of the standard of care for patients receiving solid organ transplants and is part of the immunosuppressive protocol used by kidney-pancreas transplant recipients at University Health Network (UHN). Tacrolimus is associated with several toxicities, and as a result, careful therapeutic drug monitoring of tacrolimus is a key component of post-transplant management. Trough serum concentrations of tacrolimus are measured routinely and are used to guide dosing. Tacrolimus trough levels are known to correlate with total drug exposure. The Prograf formulation of tacrolimus has a fairly short serum half-life and must be dosed twice daily to maintain therapeutic serum concentrations. This results in two high peak levels each day which have been shown to correlate with toxicity. Thus, avoidance of high peaks may be desirable to minimize tacrolimus toxicity.

Advagraf is a new preparation of tacrolimus that is formulated to provide similar drug exposure to tacrolimus but with a once daily dosing regimen, which avoids the 2 daily high tacrolimus peaks observed with Prograf. In this way, it is hoped that Advagraf may provide similar therapeutic efficacy as Prograf but with fewer adverse effects. In addition, the simpler dosing regimen is expected to enhance patient adherence. Tacrolimus has also been shown, along with many other drugs, to have a variable impact on mycophenolate acid (MPA) pharmacokinetics. There are currently few data on whether Advagraf impacts MPA pharmacokinetics to the same or a lesser degree than Prograf.

Eligible kidney-pancreas recipients will be recruited and after obtaining informed consent, randomized to continue their current total daily Prograf dosage or switch to the equivalent once daily dose of Advagraf. Patients will continue randomized therapy for 12 weeks and will then cross over to the opposite therapy for another 12 weeks. Patients will be followed and maintained on the same medication designated at week 24. Bloodwork results, adherence and AEs (adverse events) will be assessed.

Conditions

Kidney-Pancreas Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prograf arm

patients will self-administer tacrolimus in the form of Prograf (twice daily administration.

Dosage will be adjusted to maintain trough serum levels of 5-15 μg/ml. Maximum daily dose of 20 mg once per day.

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

Advagraf Arm

patients will self-administer tacrolimus in the form of Advagraf (once daily dosing) Dosage will be adjusted to maintain trough serum levels of 5-15 μg/ml. Maximum daily dose of 20 mg once per day.

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

Interventions

Tacrolimus

Intervention Type: DRUG

Tacrolimus

Intervention Type: DRUG

Other Intervention Names

Prograf; Advagraf

Eligibility Criteria

Inclusion Criteria

• recipient of kidney and pancreas transplant
• aged 18 years or older
• 12 months or more since time of transplant
• stable allograft function (creatinine < 180 µmol/l and eGFR > 40 ml/min)
• targeted to a tacrolimus trough level of 5-10 ug/ml that has been stable during the prior 3 mo.

Exclusion Criteria

• episode of acute rejection within 6 months of screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark S Cattral, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Toronto General Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

12-0330-B

Identifier Type: -

Identifier Source: org_study_id