A Comparison of the Effects of Extended Release Tacrolimus (Advagraf®) vs. Immediate Release Tacrolimus (Prograf®) on Kidney Function in Healthy Male Volunteers

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the drug profiles (pharmacokinetics) and effects (pharmacodynamics) of Advagraf® and Prograf® on the kidneys.

Detailed Description
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This is a 2 Period study. In Period 1, subjects will be assigned randomly to receive Advagraf® or Prograf® administered once or twice daily, respectively, for a period of 10 days. In Period 2, subjects will be converted from Advagraf® to Prograf® or from Prograf® to Advagraf® for 10 additional days of dosing. Dose adjustments will be made based on the monitoring of drug levels in blood.

Official Title
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A Comparison of Effects of Short-Term Steady State Low Dose Exposure of Extended Release (Advagraf®) and Immediate Release (Prograf®) Formulations of Tacrolimus on Renal Perfusion and Function in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Advagraf®
* Drug: Prograf®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian No previous/current history of infection, cerebrovascular, neurological, cardiovascular, endocrine, pulmonary, immunologic or metabolic disease or significant systemic disease, glucose intolerance, gout or hematological disorder Normal 12-lead Electrocardiogram (ECG) Systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg Non-smoker within 3 months prior to screening Willing to abstain from alcohol during the study Exclusion Criteria: Positive screen for illicit drug or alcohol consumption Subject has hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or history of cancer (excluding completely excised squamous or basal cell carcinoma) Positive tuberculin skin test or known history of tuberculosis infection Known history of serious head injuries, seizures or eating disorders Body Mass Index <18.0 or >30.0 History of renal dysfunction, clinically significant creatinine or clinically significant abnormal liver function tests, hemoglobin <130 g/L Plasma donation ≥ 500 mL within 7 days prior to first dose of study drug, donation or whole blood loss 50-499 mL within 30 days or ≥ 499 mL within 56 days prior to first dose of study drug. Drug or alcohol abuse within 1 year prior to study entry Steroid injections within 12 weeks prior to first dose of study drug Live vaccine within 7 days prior to first dose of study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advagraf followed by Prograf<br> | Drug: Advagraf®<br>* oral<br>* Other names: tacrolimus XL, FK506E;Drug: Prograf®<br>* oral<br>* Other names: tacrolimus, FK506;|
| Experimental: Prograf followed by Advagraf<br> | Drug: Advagraf®<br>* oral<br>* Other names: tacrolimus XL, FK506E;Drug: Prograf®<br>* oral<br>* Other names: tacrolimus, FK506;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective Renal Plasma Flow (ERPF) | Estimated by aminohippurate sodium (PAH) clearance | up to Day 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular Filtration Rate (GFR) | Estimated by sinistrin clearance | Pre-dose (Day -4), Day 10, Day 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tacrolimus, Advagraf®, Prograf®, Glomerular Filtration Rate, Effective Renal Plasma Flow, Pharmacokinetics, Pharmacodynamics