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

• Sponsor: University Medicine Greifswald (Other)
• Overall Status: Completed
• CT.gov ID: NCT00810303
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 4
• Patients Per Site Per Month: 3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics; Drug Interactions; Pharmacodynamics; Intestinal Transporter Expression	Drug: Ezetrol (ezetimibe) multiple dose; Drug: Ezetrol (ezetimibe) multiple dose and Sustiva (efavirenz) single dose; Drug: Ezetrol (ezetimibe) and Sustiva (efavirenz) multiple dose; Drug: Sustiva (efavirenz) single dose	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

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

Drug: 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)); Other Names: Ezetrol ; 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); Other Names: Ezetrol+Sustiva single dose ; 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); Other Names: Ezetrol+Sustiva steady state ; 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); Other Names: Sustiva

Outcome Measures

Primary Outcome Measures

1. AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 [study day 15]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.

2. AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 [study day 16]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.

3. AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 [study day 30]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.

4. Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 [study day 15]

   The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.

5. Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 [study day 16]

   The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.

6. Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 [study day 30]

   The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.

7. AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 [study days 1-5]

   The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.

8. AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 [study days 16-20]

   The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.

9. AUC0-24h of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 [study day 30]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.

10. Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 [study days 1-5]

    The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.

11. Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 [study days 16-20]

    The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.

12. Cmax of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 [study day 30]

    The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.

Secondary Outcome Measures

1. AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 [study day 15]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.

2. AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 [study day 16]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.

3. AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 [study day 30]

   The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.

4. Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 [study day 15]

   The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.

5. Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 [study day 16]

   The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.

6. Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 [study day 30]

   The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Department of Clinical Pharmacology	Greifswald		Germany	17489

Sponsors and Collaborators

• University Medicine Greifswald

Investigators

• Principal Investigator: Werner Siegmund, Prof, Department of Clinical Pharmacology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00810303
• Other Study ID Numbers: Efavirenz - 2008
• First Posted: Dec 18, 2008
• Last Update Posted: Oct 11, 2010
• Last Verified: Sep 1, 2010

• Additional relevant MeSH terms: Efavirenz; Ezetimibe

Study Results

Participant Flow

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Period Title: Efavirenz Alone - Day 1-5
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: Efavirenz Alone - Day 1-5
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: Efavirenz Alone - Day 1-5
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: Efavirenz Alone - Day 1-5
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26 (4.6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Region of Enrollment (participants) [Number]
Germany	12 100%

Outcome Measures

1. Primary Outcome

Title	AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time Frame	study day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	51.9 (21.7)

2. Primary Outcome

Title	AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time Frame	study day 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	58.6 (23.7)

3. Primary Outcome

Title	AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time Frame	study day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	51.2 (23.1)

4. Primary Outcome

Title	Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time Frame	study day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	4.82 (2.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time Frame	study day 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	5.54 (2.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time Frame	study day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	4.46 (2.07)

7. Primary Outcome

Title	AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5
Description	The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time Frame	study days 1-5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	29.7 (15.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Primary Outcome

Title	AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20
Description	The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time Frame	study days 16-20

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	27.0 (12.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz with chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Primary Outcome

Title	AUC0-24h of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time Frame	study day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	11.4 (4.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz with chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Primary Outcome

Title	Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time Frame	study days 1-5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	0.622 (0.244)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Primary Outcome

Title	Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time Frame	study days 16-20

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	0.659 (0.395)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetics of efavirenz with chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Primary Outcome

Title	Cmax of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time Frame	study day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	0.918 (0.342)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetics of efavirenz with chronic treatment of ezetimibe.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time Frame	study day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	466 (223)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time Frame	study day 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	411 (195)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
Description	The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time Frame	study day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng*h/ml]	325 (152)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Secondary Outcome

Title	Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time Frame	study day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	79.0 (43.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

17. Secondary Outcome

Title	Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time Frame	study day 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	60.9 (29.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

18. Secondary Outcome

Title	Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
Description	The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time Frame	study day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	whole study group: 12 healthy subjects
Measure Participants	12
Mean (Standard Deviation) [ng/ml]	45.3 (14.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments	Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Study Group		Efavirenz Alone Single Dose		Ezetimibe Alone Multiple Dose		Ezetimibe Multiple Dose and Efavirenz Single Dose		Ezetimibe and Efavirenz Multiple Dose
Arm/Group Description	whole study group: 12 healthy subjects
All Cause Mortality
	Study Group		Efavirenz Alone Single Dose		Ezetimibe Alone Multiple Dose		Ezetimibe Multiple Dose and Efavirenz Single Dose		Ezetimibe and Efavirenz Multiple Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Study Group		Efavirenz Alone Single Dose		Ezetimibe Alone Multiple Dose		Ezetimibe Multiple Dose and Efavirenz Single Dose		Ezetimibe and Efavirenz Multiple Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Study Group		Efavirenz Alone Single Dose		Ezetimibe Alone Multiple Dose		Ezetimibe Multiple Dose and Efavirenz Single Dose		Ezetimibe and Efavirenz Multiple Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		8/12 (66.7%)		3/12 (25%)		7/12 (58.3%)		7/12 (58.3%)
Gastrointestinal disorders
Belly ache	2/12 (16.7%)	2	2/12 (16.7%)	2	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Diarrhoea NOS	2/12 (16.7%)	2	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	2/12 (16.7%)	2
Nausea	2/12 (16.7%)	2	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Upper abdominal discomfort	1/12 (8.3%)	1	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
General disorders
Hot flushes	1/12 (8.3%)	1	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Metabolism and nutrition disorders
Plasma triglycerides increased	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Headache NOS	5/12 (41.7%)	11	4/12 (33.3%)	4	3/12 (25%)	3	0/12 (0%)	0	3/12 (25%)	4
Lightheadedness	10/12 (83.3%)	18	5/12 (41.7%)	5	0/12 (0%)	0	7/12 (58.3%)	7	6/12 (50%)	6
Restlessness	2/12 (16.7%)	2	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	2/12 (16.7%)	2
Psychiatric disorders
Concentration impairment	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Confusion	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Nightmare	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Sleep disorder	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Renal and urinary disorders
Renal pain	1/12 (8.3%)	2	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.