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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 has been completed.
First Received: December 17, 2008   Last Updated: July 31, 2009   History of Changes
Sponsor: 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

Study Type: Interventional
Study Design: Basic Science, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study

Resource links provided by NLM:


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
Study Completion Date: July 2009
Primary Completion Date: July 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

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: July 31, 2009
ClinicalTrials.gov Identifier: NCT00810303     History of Changes
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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 March 16, 2010