Clinical trial NCT01681134: A Comparison of the Effects of Extended Release Tacrolimus (Advagraf®) vs. Immediate Release Tacrolimus (Prograf®) on Kidney Function in Healthy Male Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: tacrolimus
Advagraf®
Prograf®
Glomerular Filtration Rate
Effective Renal Plasma Flow
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-09-07
Enrollment: 19
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effective Renal Plasma Flow (ERPF)
timeFrame: up to Day 20
Secondary outcomes:
measure: Glomerular Filtration Rate (GFR)
timeFrame: Pre-dose (Day -4), Day 10, Day 20
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: INC Research
state: Ontario
Study officials:
affiliation: Astellas Pharma Canada, Inc.
name: Associate Director, Medical Affairs
role: STUDY_DIRECTOR
References:
citation: Zaltzman JS, Lai V, Schulz MZ, Moon KH, Cherney DZ. A randomized cross-over comparison of short-term exposure of once-daily extended release tacrolimus and twice-daily tacrolimus on renal function in healthy volunteers. Transpl Int. 2014 Dec;27(12):1294-302. doi: 10.1111/tri.12435. Epub 2014 Sep 29.