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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Advagraf®; Drug: Prograf®

• Registration Number: NCT01681134
• Lead Sponsor: Astellas Pharma Canada, Inc.

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.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-09-05
• Study First Submitted QC: 2012-09-06
• Study First Posted: 2012-09-07
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-06
• Last Update Posted: 2012-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Advagraf followed by Prograf	Advagraf®	-
Advagraf followed by Prograf	Prograf®	-
Prograf followed by Advagraf	Advagraf®	-
Prograf followed by Advagraf	Prograf®	-

Primary Outcome Measures

Name	Time	Method
Effective Renal Plasma Flow (ERPF)	up to Day 20	Estimated by aminohippurate sodium (PAH) clearance

Secondary Outcome Measures

Name	Time	Method
Glomerular Filtration Rate (GFR)	Pre-dose (Day -4), Day 10, Day 20	Estimated by sinistrin clearance

Trial Locations

Locations (1)

INC Research; 🇨🇦 Toronto, Ontario, Canada