Trial Outcomes & Findings for Effects of Ezetimibe on the Absorption of Oxidized Cholesterol (NCT NCT00794677)

NCT ID: NCT00794677

Last Updated: 2021-03-09

Results Overview

Log of Area-under-the-plasma-concentration curve (AUC 0-8hrs) of 7-ketocholesterol after an oral bolus in patients with primary hypercholesterolemia after treatment with ezetimibe versus placebo

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 26 participants
• Primary outcome timeframe: 6 weeks
• Results posted on: 2021-03-09

Participant Flow

Recruitment took place in 2007 through search of a clinical research center database, mailings to homes, and posted flyers in the Berkeley, California area.

55 participants screened; 29 excluded because they did not meet inclusion criteria

Participant milestones

Measure	Placebo First Placebo once daily in first intervention period and ezetimibe (10 mg/day) in second intervention period	Ezetimibe First Ezetimibe (10 mg/day) once daily in the first intervention period and placebo once daily in the second intervention period
First Intervention STARTED	13	13
First Intervention COMPLETED	11	13
First Intervention NOT COMPLETED	2	0
Second Intervention STARTED	11	13
Second Intervention COMPLETED	11	13
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Placebo First Placebo once daily in first intervention period and ezetimibe (10 mg/day) in second intervention period	Ezetimibe First Ezetimibe (10 mg/day) once daily in the first intervention period and placebo once daily in the second intervention period
First Intervention Withdrawal by Subject	2	0

Baseline Characteristics

Effects of Ezetimibe on the Absorption of Oxidized Cholesterol

Baseline characteristics by cohort

Measure	Ezetimibe n=11 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=13 Participants Placebo once daily received as the first or second intervention	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants	11 Participants n=4 Participants	22 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Age, Continuous	52.05 years STANDARD_DEVIATION 7.54 • n=93 Participants	50.09 years STANDARD_DEVIATION 14.28 • n=4 Participants	50.99 years STANDARD_DEVIATION 11.49 • n=27 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	11 Participants n=4 Participants	18 Participants n=27 Participants
Region of Enrollment United States	11 participants n=93 Participants	13 participants n=4 Participants	24.0 participants n=27 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: per protocol

Log of Area-under-the-plasma-concentration curve (AUC 0-8hrs) of 7-ketocholesterol after an oral bolus in patients with primary hypercholesterolemia after treatment with ezetimibe versus placebo

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Log[Area-under-the-plasma-concentration-curve(AUC) 0-8 Hours 7-ketocholesterol] After an Oral Bolus	1.925 Log(mg*hr/dl) Standard Error 0.166	2.177 Log(mg*hr/dl) Standard Error 0.142

SECONDARY outcome

Timeframe: 6 weeks

Population: Per protocol

Log Cmax of 7 ketocholesterol after an oral bolus in patients with primary hypercholesterolemia.

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Log(Maximal Plasma Concentration (Cmax) of 7-ketocholesterol) After an Oral Bolus	0.973 Log(mg/dl) Standard Error 0.156	1.246 Log(mg/dl) Standard Error 0.133

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Population: Per protocol

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Log(Fasting Plasma Levels of Diet-derived Oxysterols (7-ketocholesterol))	-1.119 Log(mg/dl) Standard Error 0.124	-1.070 Log(mg/dl) Standard Error 0.107

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Population: Per protocol, restricted to changes that were nonnegative because there is no log for a negative number

Area under the curve (AUC) calculated over 8 hours

Outcome measures

Measure	Ezetimibe n=9 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=9 Participants Placebo once daily received as the first or second intervention
Log (AUC of Plasma Total Cholesterol) After an Oral Bolus	2.928 Log(mg*hr/dl) Standard Error 0.213	2.719 Log(mg*hr/dl) Standard Error 0.346

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Population: Per protocol, one subject eliminated because the AUC was negative and cannot be log transformed

Area under the curve (AUC) calculated over 8 hours

Outcome measures

Measure	Ezetimibe n=23 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=23 Participants Placebo once daily received as the first or second intervention
Log (AUC of Plasma Triglyceride) After an Oral Bolus	4.894 Log(mg*hr/dl) Standard Error 0.139	5.044 Log(mg*hr/dl) Standard Error 0.126

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (placebo run-in) and 6 weeks

Population: Per protocol

Change = [(Week 6 - baseline)/baseline value *100]

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Percent Change of Fasting Apolipoprotein B From Baseline	-17.990 percent change from baseline Standard Error 1.648	-2.577 percent change from baseline Standard Error 2.113

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (placebo run-in) and 6 weeks

Population: Per protocol

Change = [(Week 6 - baseline)/baseline value *100]

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Percent Change of Fasting Low Density Lipoprotein Cholesterol From Baseline	-22.891 percent change from baseline Standard Error 2.497	-1.045 percent change from baseline Standard Error 2.454

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (placebo run-in) and 6 weeks

Population: Per protocol

Change = [(Week 6 - baseline)/baseline value *100]

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Percent Change in Fasting High Density Lipoprotein Cholesterol	-1.936 percent change from baseline Standard Error 2.134	-7.333 percent change from baseline Standard Error 1.860

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (placebo run-in) and 6 weeks

Population: Per protocol

Change = [(Week 6 - baseline)/baseline value *100]

Outcome measures

Measure	Ezetimibe n=24 Participants Ezetimibe (10 mg/day) once daily received as the first or second intervention	Placebo n=24 Participants Placebo once daily received as the first or second intervention
Percent Change of Fasting Non-high Density Lipoprotein Cholesterol From Baseline	-22.675 percent change from baseline Standard Error 2.326	-1.322 percent change from baseline Standard Error 1.871

Adverse Events

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Ronald M Krauss

Children's Hospital Oakland Research Institute

Phone: 510.450.7912

Email: rkrauss@chori.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place