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

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma Canada, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00818194
First received: January 6, 2009
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Healthy
Drug: extended release tacrolimus
Drug: cyclosporine A microemulsion
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Comparison of Effects of Short-term Low Dose Exposure of Advagraf® and Neoral® Microemulsion Cyclosporine A on Renal Perfusion and Function in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Comparison of Effective Renal Plasma Flow response [ Time Frame: Baseline and Day 10 of each dosing interval ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of Glomerular Filtration Rate response [ Time Frame: Baseline and Day 10 of each dosing interval ] [ Designated as safety issue: No ]
  • Comparison of blood pressure response [ Time Frame: Baseline and Day 10 of each dosing interval ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: April 2008
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A. tacrolimus first
Subjects receive extended release tacrolimus in first dosing interval then cross over to cyclosporine A for second dosing interval
Drug: extended release tacrolimus
oral
Other Names:
  • Advagraf®
  • FK506E
  • MR4
Drug: cyclosporine A microemulsion
oral
Other Name: Neoral®
Experimental: B. cyclosporine first
Subjects receive cyclosporine A in first dosing interval then cross over to extended release tacrolimus for second dosing interval
Drug: extended release tacrolimus
oral
Other Names:
  • Advagraf®
  • FK506E
  • MR4
Drug: cyclosporine A microemulsion
oral
Other Name: Neoral®

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00818194

Locations
Canada, Quebec
Montreal, Quebec, Canada, H3X 2H9
Sponsors and Collaborators
Astellas Pharma Inc
Astellas Pharma Canada, Inc.
Investigators
Study Director: Use Central Contact Astellas Pharma Canada, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00818194     History of Changes
Other Study ID Numbers: FKC-012, Health Canada Control # 119562
Study First Received: January 6, 2009
Last Updated: July 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by Astellas Pharma Inc:
Tacrolimus
cyclosporine A
renal plasma flow
glomerular filtration rate
human
pharmacodynamics
pharmacokinetics
Pharmacodynamics of tacrolimus

Additional relevant MeSH terms:
Cyclosporine
Cyclosporins
Tacrolimus
Anti-Infective Agents
Antifungal Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014