Prograf-Advagraf Cross Over Conversion Study

Prograf/Advagraf Conversion Study in Kidney Pancreas Transplant Recipients

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.

Study Overview

• Status: Completed
• Conditions: Kidney-Pancreas Transplantation
• Intervention / Treatment: Drug: Tacrolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Tacrolimus; Other Names: Advagraf
Experimental: 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.	Drug: Tacrolimus; Other Names: Advagraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tacrolimus trough levels	Serum trough levels	prior to conversion and 12 weeks post-conversion
Change in Renal Function	Serum creatinine and urea levels	prior to conversion and 12 weeks post-conversion
Change in Tacrolimus dosage (week 12 compared to week 24)		week 12 and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting glucose	serum fasting glucose levels	prior to conversion and 12 weeks post-conversion
Lipid profile	Cholesterol, etc...	prior to conversion and 12 weeks post-conversion
blood pressure	Cuff blood pressure readings	prior to conversion and 12 weeks post-conversion
Drug Adherence	patient self-reported drug adherence	assessed at weeks 12 and 24
Number of Participants with Adverse Events as a Measure of Safety and Tolerability"	at every visit, patients will be asked about and assessed for any adverse event development	at week 12 and week 24

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Mark S Cattral, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: February 11, 2013
• First Submitted That Met QC Criteria: February 21, 2013
• First Posted (Estimate): February 22, 2013

Study Record Updates

• Last Update Posted (Estimate): September 18, 2014
• Last Update Submitted That Met QC Criteria: September 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Renal Transplantation; Tacrolimus; Prograf; Kidney transplantation; Pancreas Transplantation; Advagraf; Drug Adherence
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 12-0330-B