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Pharmacokinetic and Pharmacodynamic Interactions Between the Cholesterol-Lowering Ezetimibe and the Non-Nucleoside Reverse Transcriptase Inhibitor Efavirenz During Chronic Treatment in Healthy Volunteers With Reference to Intestinal Expression of CYP3A4, UGT1A1, ABCB1 and ABCC2
This study is not yet open for participant recruitment.
Verified by Ernst Moritz Arndt University of Greifswald, December 2008
First Received: December 17, 2008   No Changes Posted
Sponsored by: Ernst Moritz Arndt University of Greifswald
Information provided by: Ernst Moritz Arndt University of Greifswald
ClinicalTrials.gov Identifier: NCT00810303
  Purpose

The purpose of this study is to evaluate the effects of a chronic co-medication of efavirenz on pharmacokinetics and sterol-lowering effects of ezetimibe at steady-state in healthy subjects genotyped for ABCB1, ABCC2, CYP2B6 and UGT1A1.


Condition Intervention Phase
Pharmacokinetics
Drug Interactions
Pharmacodynamics
Intestinal Transporter Expression
Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany
Drug: 1 tablet Ezetrol(R) + 2 capsules Sustiva(R) (efavirenz) single dose, DuPont Pharma
Drug: tablet Ezetrol(R) and 2 capsules Sustiva(R) steady state
Phase I

MedlinePlus related topics: Urine and Urination
Drug Information available for: Efavirenz Ezetimibe
U.S. FDA Resources
Study Type: Interventional
Study Design: Basic Science, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study

Further study details as provided by Ernst Moritz Arndt University of Greifswald:

Primary Outcome Measures:
  • Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for efavirenz: AUC0-∞, Cmax [ Time Frame: march 2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Second. characteristics: for ezetimibe and efavirenz: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and efavirenz: AUC0-t, t½, tmax [ Time Frame: march 2010 ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: March 2009
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Active Comparator
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) on study day 1-9
Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe)on study day 1-9
B: Experimental
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) on study day 10-14 and 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 10
Drug: 1 tablet Ezetrol(R) + 2 capsules Sustiva(R) (efavirenz) single dose, DuPont Pharma
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) on study say 10-14 and 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 10, 0-120 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-4 d feces sampling
C: Experimental
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) and 2 capsules/day Sustiva(R) (2x200 mg efavirenz) on study day 15-28
Drug: tablet Ezetrol(R) and 2 capsules Sustiva(R) steady state
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) and 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 15-28, 0-120 h blood sampling, urine sampling (24 h intervals) on study day 28 and feces sampling on study day 24-29

  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 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:

  • existing cardiac or haematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
  • existing hepatic and renal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
  • existing gastrointestinal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
  • 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 anti-HIV-test, HBs-Ag-test or anti-HCV-test
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00810303

Contacts
Contact: Christiane Modeß, Dr +49 (0)3834 865659 chrimo@uni-greifswald.de
Contact: Andrea Werzner +49 (0)3834 865622 werzner@uni-greifswald.de

Locations
Germany
Department of Clinical Pharmacology
Greifswald, Germany, 17489
Sponsors and Collaborators
Ernst Moritz Arndt University of Greifswald
Investigators
Principal Investigator: Werner Siegmund, Prof Department of Clinical Pharmacology
  More Information

No publications provided

Responsible Party: Organization: Department of Clinical Pharmacology ( Prof. Dr. W. Siegmund, MD )
Study ID Numbers: Efavirenz - 2008
Study First Received: December 17, 2008
Last Updated: December 17, 2008
ClinicalTrials.gov Identifier: NCT00810303     History of Changes
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Study placed in the following topic categories:
Antimetabolites
Efavirenz
Anti-HIV Agents
Anti-Retroviral Agents
Antilipemic Agents
Ezetimibe
Anticholesteremic Agents
Healthy
Antiviral Agents
Reverse Transcriptase Inhibitors

Additional relevant MeSH terms:
Antimetabolites
Efavirenz
Anti-Infective Agents
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Ezetimibe
Enzyme Inhibitors
Anticholesteremic Agents
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 07, 2009