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

NCT ID: NCT00810303

Last Updated: 2010-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2009-07-31

Brief Summary

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.

Conditions

Pharmacokinetics; Drug Interactions; Pharmacodynamics; Intestinal Transporter Expression

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

whole study group

A study with a duration of 34 days with 4 periods (= 4 pharmakokinetics) on 12 healthy subjects.

Group Type: EXPERIMENTAL

Ezetrol (ezetimibe) multiple dose

Intervention Type: DRUG

administration of 1 tablet/day Ezetrol (10 mg ezetimibe) on study day 6-15 and a pharmakokinetic on study day 15 (0-24 h blood sampling, 0-24 h urine sampling and 5 d feces sampling (study day 11-15))

Ezetrol (ezetimibe) multiple dose and Sustiva (efavirenz) single dose

Intervention Type: DRUG

administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) on study day 16-20 and 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 16 with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) and feces sampling on study days 16-20)

Ezetrol (ezetimibe) and Sustiva (efavirenz) multiple dose

Intervention Type: DRUG

administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) and 2 capsules/day Sustiva(R) (2x200 mg efavirenz) on study day 21-30 and with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) on study day 30 and feces sampling on study day 26-30)

Sustiva (efavirenz) single dose

Intervention Type: DRUG

administration of 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 1 with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) and feces sampling on study days 1-5)

Interventions

Ezetrol (ezetimibe) multiple dose

administration of 1 tablet/day Ezetrol (10 mg ezetimibe) on study day 6-15 and a pharmakokinetic on study day 15 (0-24 h blood sampling, 0-24 h urine sampling and 5 d feces sampling (study day 11-15))

Intervention Type: DRUG

Ezetrol (ezetimibe) multiple dose and Sustiva (efavirenz) single dose

administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) on study day 16-20 and 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 16 with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) and feces sampling on study days 16-20)

Intervention Type: DRUG

Ezetrol (ezetimibe) and Sustiva (efavirenz) multiple dose

administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) and 2 capsules/day Sustiva(R) (2x200 mg efavirenz) on study day 21-30 and with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) on study day 30 and feces sampling on study day 26-30)

Intervention Type: DRUG

Sustiva (efavirenz) single dose

administration of 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 1 with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) and feces sampling on study days 1-5)

Intervention Type: DRUG

Other Intervention Names

Ezetrol; Ezetrol+Sustiva single dose; Ezetrol+Sustiva steady state; Sustiva

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Medicine Greifswald

OTHER

Sponsor Role: lead

Responsible Party

Organization: Department of Clinical Pharmacology

Principal Investigators

Werner Siegmund, Prof

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Pharmacology

Locations

Department of Clinical Pharmacology

Greifswald, , Germany

Countries

Germany

Other Identifiers

Efavirenz - 2008

Identifier Type: -

Identifier Source: org_study_id