Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects

February 12, 2008 updated by: University Medicine Greifswald
The purpose of this study is to confirm a significant influence of ezetimibe and tacrolimus on each others pharmacokinetics

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hypercholesterolemia is a frequent finding in organ transplant recipients receiving immunosuppressive drugs such as tacrolimus. To prevent increased cardiovascular morbidity and mortality in these patients, co-medication with lipid-lowering statins is recommended. However, treatment with statins is limited in many patients by insufficient cholesterol-lowering efficacy, drug interactions and serious adverse drug reactions (e.g. rhabdomyolysis). These patients may benefit from comedication with the cholesterol absorption inhibitor ezetimibe. Since tacrolimus and ezetimibe were shown to be substrates of the efflux transporter ABCB1 (P-glycoprotein), drug interactions between both compounds may occur. Therefore, this clinical study in healthy subjects was initiated to evaluate the clinical relevance of drug/drug interactions between tacrolimus and ezetimibe according to the accepted bioequivalence approach.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Greifswald, Germany, 17487
        • Department of Clinical Pharmacology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age: 18 - 45 years
  • sex: male and female
  • ethnic origin: Caucasian
  • body weight: 19 kg/m² to 27 kg/m²
  • good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
  • written informed consent

Exclusion Criteria:

  • known allergy to macrolide antibiotics
  • existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
  • existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
  • existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
  • acute or chronic diseases which could affect drug absorption or metabolism
  • history of any serious psychological disorder
  • drug or alcohol dependence
  • positive drug or alcohol screening
  • smokers of 10 or more cigarettes per day
  • positive screening results for HIV, HBV and HCV
  • volunteers who are on a diet which could affect the pharmacokinetics of the drug
  • heavy tea or coffee drinkers (more than 1L per day)
  • lactation and pregnancy test positive or not performed
  • volunteers suspected or known not to follow instructions
  • volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
  • volunteers liable to orthostatic dysregulation, fainting, or blackouts
  • blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study
  • participation in a clinical trial during the last 3 months prior to the start of the study
  • less than 14 days after last acute disease
  • any systemically available medication within 4 weeks prior to the intended first administration unless, because of the terminal elimination half-life, complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
  • repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)
  • repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists)
  • intake of grapefruit containing food or beverages within 7 days prior to administration
  • known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation
  • subjects with severe allergies or multiple drug allergies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: C
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 1 capsule Prograf(R) (5 mg tacrolimus)
Drug: 1 tablet Ezetrol(R) + 1 capsules Prograf(R)
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 1 capsule Prograf(R) (5 mg Tacrolimus), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
Other Names:
  • Ezetrol+Prograf
ACTIVE_COMPARATOR: A
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe)
Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
Other Names:
  • Ezetrol
ACTIVE_COMPARATOR: B
administration of 1 capsule Prograf(R) (5 mg tacrolimus)
Drug: 1 capsule Prograf(R) (tacrolimus), Astellas Pharma GmbH, Germany
administration of 1 capsule Prograf(R) (5 mg tacrolimus), 0-144 h blood sampling
Other Names:
  • Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for tacrolimus: AUC0-∞, Cmax
Time Frame: September 2007 to November 2007
September 2007 to November 2007

Secondary Outcome Measures

Outcome Measure
Time Frame
Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and tacrolimus: AUC0-t, t½, tmax
Time Frame: September 2007 to November 2007
September 2007 to November 2007

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medicine Greifswald

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (ACTUAL)

November 1, 2007

Study Completion (ACTUAL)

November 1, 2007

Study Registration Dates

First Submitted

February 12, 2008

First Submitted That Met QC Criteria

February 12, 2008

First Posted (ESTIMATE)

February 22, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

February 22, 2008

Last Update Submitted That Met QC Criteria

February 12, 2008

Last Verified

February 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Eze-Tacro
  • 2006-006549-14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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