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

This study has been completed.
Sponsor:
Information provided by:
University Medicine Greifswald
ClinicalTrials.gov Identifier:
NCT00621101
First received: February 12, 2008
Last updated: NA
Last verified: February 2008
History: No changes posted
  Purpose

The purpose of this study is to confirm a significant influence of ezetimibe and sirolimus on each others pharmacokinetics


Condition Intervention Phase
Pharmacokinetics
Drug Interactions
Hypercholesterolemia
Immunosuppression
Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany
Drug: 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany
Drug: 1 tablet Ezetrol(R) + 1 tablet Rapamune(R)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pharmacokinetic Drug Interaction Between Ezetimibe and Sirolimus After Single Dose Administration in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by University Medicine Greifswald:

Primary Outcome Measures:
  • Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for sirolimus: AUC0-∞, Cmax [ Time Frame: April 2007 to June 2007 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and sirolimus: AUC0-t, t½, tmax [ Time Frame: April 2007 to June 2007 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2007
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ezetrol
Active Comparator: B
administration of 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus)
Drug: 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany
administration of 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus), 0-144 h blood sampling
Other Name: Rapamune
Experimental: C
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus)
Drug: 1 tablet Ezetrol(R) + 1 tablet Rapamune(R)
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
Other Name: Ezetrol+Rapamune

Detailed Description:

Hypercholesterolemia is a frequent finding in organ transplant recipients receiving immunosuppressive drugs such as sirolimus. 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 (EZE). Since SIR and EZE 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 sirolimus and ezetimibe according to the accepted bioequivalence approach.

  Eligibility

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

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
  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: NCT00621101

Locations
Germany
Department of Clinical Pharmacology
Greifswald, Germany, 17487
Sponsors and Collaborators
University Medicine Greifswald
Investigators
Principal Investigator: Werner Siegmund, Prof Department of Clinical Pharmacology
  More Information

No publications provided

Responsible Party: Prof. Dr. W. Siegmund, MD, Department of Clinical Pharmacology
ClinicalTrials.gov Identifier: NCT00621101     History of Changes
Other Study ID Numbers: Eze-Siro, EudraCT-No. 2006-006597-18
Study First Received: February 12, 2008
Last Updated: February 12, 2008
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Medicine Greifswald:
pharmacokinetics
drug interactions
ezetimibe
sirolimus
human experimentation

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Everolimus
Ezetimibe
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Anticholesteremic Agents
Antifungal Agents
Antimetabolites
Antineoplastic Agents
Hypolipidemic Agents
Immunologic Factors
Immunosuppressive Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014