Trial Outcomes & Findings for 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 NCT00810303)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

study day 15

Results posted on

2010-10-11

Participant Flow

Participant milestones

Participant milestones
Measure	Study Group whole study group: 12 healthy subjects
Efavirenz Alone - Day 1-5 STARTED	12
Efavirenz Alone - Day 1-5 COMPLETED	12
Efavirenz Alone - Day 1-5 NOT COMPLETED	0
Ezetimibe Alone - Day 6-15 STARTED	12
Ezetimibe Alone - Day 6-15 COMPLETED	12
Ezetimibe Alone - Day 6-15 NOT COMPLETED	0
Ezetimibe and Efavirenz - Day 16-20 STARTED	12
Ezetimibe and Efavirenz - Day 16-20 COMPLETED	12
Ezetimibe and Efavirenz - Day 16-20 NOT COMPLETED	0
Ezetimibe and Efavirenz - Day 21-30 STARTED	12
Ezetimibe and Efavirenz - Day 21-30 COMPLETED	12
Ezetimibe and Efavirenz - Day 21-30 NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	26 years STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Region of Enrollment Germany	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15	51.9 ng*h/ml Standard Deviation 21.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	58.6 ng*h/ml Standard Deviation 23.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	51.2 ng*h/ml Standard Deviation 23.1

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15	4.82 ng/ml Standard Deviation 2.74

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	5.54 ng/ml Standard Deviation 2.65

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	4.46 ng/ml Standard Deviation 2.07

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5	29.7 ng*h/ml Standard Deviation 15.4

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	27.0 ng*h/ml Standard Deviation 12.2

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	11.4 ng*h/ml Standard Deviation 4.64

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5	0.622 ng/ml Standard Deviation 0.244

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	0.659 ng/ml Standard Deviation 0.395

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	0.918 ng/ml Standard Deviation 0.342

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15	466 ng*h/ml Standard Deviation 223

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	411 ng*h/ml Standard Deviation 195

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	325 ng*h/ml Standard Deviation 152

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15	79.0 ng/ml Standard Deviation 43.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Study Group n=12 Participants whole study group: 12 healthy subjects
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	60.9 ng/ml Standard Deviation 29.5

SECONDARY outcome

Timeframe: 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.