Comparison of Extended Release Tacrolimus (Advagraf) and Cyclosporine A Microemulsion on Renal Function in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: extended release tacrolimus; Drug: cyclosporine A microemulsion

• Registration Number: NCT00818194
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

The purpose of this study is to compare the effects of steady state tacrolimus vs. cyclosporine on renal pharmacodynamics in healthy volunteers.

Detailed Description

This study seeks to evaluate the renal physiological responses of short-term maintenance level doses of CNIs in healthy volunteers to determine if daily perturbations in renal physiology exist, and if confirmed, whether they differ between CNIs and thus may contribute by different mechanisms to the progression of CAN.

Study Timeline

• Study Start: 2008-04
• Primary Completion: 2008-09
• Study Completion: 2008-09
• Study First Submitted: 2009-01-06
• Study First Submitted QC: 2009-01-06
• Study First Posted: 2009-01-07
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-07
• Last Update Posted: 2014-07-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• caucasian
• healthy with no history or current clinical findings of infection or disease of the following nature: cerebrovascular, neurologic, cardiovascular, endocrine, pulmonary, immunologic, metabolic, hematologic, diabetes mellitus, glucose intolerance, gout
• non-smoker and willing to abstain from alcohol consumption during the study
• agrees to use appropriate contraception during the study period until 3 months after the final study exam.

Exclusion Criteria

• history of significant alcohol abuse or drug abuse within 1 year prior to the screening visit
• regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week)
• use of soft drugs (marijuana) within 3 months prior to the screening visit or hard drugs (cocaine, PCP, crack) within 1 year prior to the screening visit Hepatitis B or C, HIV, history of cancer (excluding excised squamous or basal cell carcinoma)
• positive tuberculin skin test or prior TB infection
• known history of serious head injuries, seizures or any eating disorder
• received an investigational drug within 30 days prior to the first study drug administration
• known hypersensitivity/allergy to tacrolimus, cyclosporine, iothalamate iodine, para-aminohippuric acid, antibiotics or antifungals
• Body mass index (BMI) <19 or >27
• clinically significant history of psychiatric disease or a significant disability that prevents understanding or adherence to protocol
• renal dysfunction, serum creatinine or urine microalbumin above the normal age and gender-adjusted reference range of the local lab
• clinically significant abnormal liver function test indicative of impaired hepatic function
• received medications/herbal preparations that may affect the metabolism of tacrolimus or cyclosporine A within 1 month of the first study drug administration
• received any other prescription medication within 14 days prior to the first study drug administration or any over-the-counter product within 7 days prior to the first study drug administration, except for topical products without systemic absorption
• current GI condition known to affect GI motility and/or absorption
• donation of plasma (500 mL) within 7 days prior to the first study drug administration or donation/ loss of whole blood as follows: 50 mL to 499 mL within 30 days or more than 499 mL within 56 days prior to the first study drug administration
• clinically significant surgery within 4 weeks prior to the first study drug administration
• administration of steroids by injection within 12 weeks prior to the first study drug administration
• administration of any live vaccine within 7 days prior to the first study drug administration
• travel in areas where TB is endemic within 8 weeks prior to the TB skin test performed at the screening visit
• hemoglobin <140 g/L

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
A. tacrolimus first	extended release tacrolimus	Subjects receive extended release tacrolimus in first dosing interval then cross over to cyclosporine A for second dosing interval
A. tacrolimus first	cyclosporine A microemulsion	Subjects receive extended release tacrolimus in first dosing interval then cross over to cyclosporine A for second dosing interval
B. cyclosporine first	extended release tacrolimus	Subjects receive cyclosporine A in first dosing interval then cross over to extended release tacrolimus for second dosing interval
B. cyclosporine first	cyclosporine A microemulsion	Subjects receive cyclosporine A in first dosing interval then cross over to extended release tacrolimus for second dosing interval

Primary Outcome Measures

Name	Time	Method
Comparison of Effective Renal Plasma Flow response	Baseline and Day 10 of each dosing interval

Secondary Outcome Measures

Name	Time	Method
Comparison of blood pressure response	Baseline and Day 10 of each dosing interval
Comparison of Glomerular Filtration Rate response	Baseline and Day 10 of each dosing interval