Trial Outcomes & Findings for Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study (NCT NCT00701727)
NCT ID: NCT00701727
Last Updated: 2011-04-18
Results Overview
(Fecal excretion of plasma-derived cholesterol):The following measurements will be made following isotope infusion: 1. The composition of fecal neutral and acidic sterols will be measured as % of total. 2. The excretion rate of fecal neutral and acidic sterols will be measured as mg/day. 3. The isotopic enrichment of both fecal neutral and acidic sterols will be measured as atomic percent excess (% APE). 4. Fecal isotope excretion, or recovery, of plasma-derived cholesterol will be calculated as %/day.
COMPLETED
PHASE4
31 participants
7 weeks
2011-04-18
Participant Flow
Participants recruited at a research clinic, Chicago, IL, from June 2008 to October 2008
61 subjects screened, 30 subjects excluded(8 failed inclusion criteria, 9 failed exclusion criteria, 3 had unsuitable veins, 5 failed a drug screen, 1 was lost-to-follow-up, 4 were excluded when enrollment was complete), 31 subjects randomized.
Participant milestones
| Measure |
Ezetimibe First, Placebo Second
Ezetimibe first for 7 weeks, followed by placebo for 7 weeks
|
Placebo First, Ezetimibe Second
Placebo first for 7 weeks,followed by ezetimibe for 7 weeks
|
|---|---|---|
|
First Treatment Period
STARTED
|
16
|
15
|
|
First Treatment Period
COMPLETED
|
15
|
13
|
|
First Treatment Period
NOT COMPLETED
|
1
|
2
|
|
Second Treatment Period
STARTED
|
15
|
13
|
|
Second Treatment Period
COMPLETED
|
13
|
13
|
|
Second Treatment Period
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Ezetimibe First, Placebo Second
Ezetimibe first for 7 weeks, followed by placebo for 7 weeks
|
Placebo First, Ezetimibe Second
Placebo first for 7 weeks,followed by ezetimibe for 7 weeks
|
|---|---|---|
|
First Treatment Period
Adverse Event
|
0
|
0
|
|
First Treatment Period
Withdrawal by Subject
|
1
|
0
|
|
First Treatment Period
sponsor decision
|
0
|
1
|
|
First Treatment Period
Lost to Follow-up
|
0
|
1
|
|
Second Treatment Period
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Ezetimibe Reverse Cholesterol Transport (RCT) Pilot Study
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=31 Participants
Includes groups randomized to receive ezetimibe first and placebo first
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
27 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 weeksPopulation: Per Protocol,all subjects
(Fecal excretion of plasma-derived cholesterol):The following measurements will be made following isotope infusion: 1. The composition of fecal neutral and acidic sterols will be measured as % of total. 2. The excretion rate of fecal neutral and acidic sterols will be measured as mg/day. 3. The isotopic enrichment of both fecal neutral and acidic sterols will be measured as atomic percent excess (% APE). 4. Fecal isotope excretion, or recovery, of plasma-derived cholesterol will be calculated as %/day.
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
Fecal Excretion of Plasma-derived Cholesterol
|
1593 mg/day cholesterol excreted
Standard Deviation 1287
|
1950 mg/day cholesterol excreted
Standard Deviation 915
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: per protocol, all subjects
plasma levels of total cholesterol
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
Change From Baseline in Total Cholesterol, From Fasting Plasma Samples
|
219 mg/dL total cholesterol
Standard Deviation 26
|
187 mg/dL total cholesterol
Standard Deviation 24
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: per protocol, all subjects
Plasma DNC will be measured following the isotope infusion of deuterated water, expressed as %.
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
de Novo Cholesterol Synthesis (DNC)
|
3.4 %/day plasma DNC
Standard Deviation 0.1
|
4.7 %/day plasma DNC
Standard Deviation 0.1
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: per protocol, all subjects
The efflux, or mobilization, rate of cholesterol from peripheral tissues into the plasma will be measured as mg/kg/hr. An IV infusion of \[13C2\] cholesterol mixed in 10% Intralipid® and 10 % ethanol is given piggy-backed into normal saline over 20 hours (4pm - 12 noon). This is used to determine rate of appearance (Ra) cholesterol, which will be measured by dilution of infused \[13C2\] cholesterol during the plateau phase of plasma enrichment (approximately the last 4 hours of the infusion), as well as to provide the plasma cholesterol that will be traced into biliary sterols.
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
Cholesterol Efflux Rate (Ra Cholesterol)
|
4.6 mg/kg/hr cholesterol
Standard Deviation 0.5
|
4.4 mg/kg/hr cholesterol
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: per protocol, all subjects
Change from baseline in plasma triglycerides, measured in fasting blood samples
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
Triglycerides (TG)
|
128 mg/dL TG
Standard Deviation 48
|
121 mg/dL TG
Standard Deviation 50
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: per protocol, all subjects
Change from baseline in plasma low-density lipoprotein(LDL), measured in fasting blood samples
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
Low-density Lipoprotein (LDL);
|
148 mg/dL LDL
Standard Deviation 24
|
116 mg/dL LDL
Standard Deviation 20
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: per protocol, all subjects
Change from baseline in plasma HDL, measured in fasting blood samples
Outcome measures
| Measure |
Placebo
n=26 Participants
placebo daily,7 weeks
|
Ezetimibe
n=26 Participants
Ezetimibe 10 mg/day 7 weeks
|
|---|---|---|
|
High-density Lipoprotein (HDL)
|
46 mg/dL HDL
Standard Deviation 9
|
45 mg/dL HDL
Standard Deviation 11
|
Adverse Events
Placebo
Ezetimibe
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=31 participants at risk
Placebo, 10 mg/day, for 7 weeks
|
Ezetimibe
n=31 participants at risk
ezetimibe, 10 mg/day, for 7 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
9.7%
3/31 • Number of events 3 • 7 weeks
|
9.7%
3/31 • Number of events 3 • 7 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/31 • 7 weeks
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
|
Nervous system disorders
Dizziness
|
9.7%
3/31 • Number of events 3 • 7 weeks
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
|
General disorders
Fatigue
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
|
Nervous system disorders
Headache
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
3.2%
1/31 • Number of events 1 • 7 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.2%
1/31 • Number of events 1 • 7 weeks
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
|
Infections and infestations
Nasopharyngitis
|
6.5%
2/31 • Number of events 2 • 7 weeks
|
3.2%
1/31 • Number of events 1 • 7 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place