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

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

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.

• Drug: Advagraf®
  oral
  Other Name: tacrolimus XL, FK506E
• Drug: Prograf®
  oral
  Other Name: tacrolimus, FK506

• Experimental: Advagraf followed by Prograf
  Interventions:

  • Drug: Advagraf®
  • Drug: Prograf®
• Experimental: Prograf followed by Advagraf
  Interventions:

  • Drug: Advagraf®
  • Drug: Prograf®

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