Hypercholesterolemia
Conditions
Keywords
Primary Hypercholesterolemia
Brief summary
A study to evaluate the cholesterol-lowering effects of ezetimibe in participants with primary hypercholesterolemia (high cholesterol) after eating a meal that is high in cholesterol. The primary hypothesis is that treatment with ezetimibe 10 mg/day reduces the cholesterol concentration of the chylomicron-containing Sf≥400 fraction following a cholesterol-enriched test meal.
Interventions
DRUGezetimibe
DRUGComparator: placebo
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Eligible patients will be otherwise healthy men and women (if not on oral contraceptives or hormone replacement therapy) 18 through 70 years of age with moderately high cholesterol.
Exclusion criteria
* Individuals on other lipid-lowering therapy (medicines that lower cholesterol) including statins (within 6 weeks) and fibrates (within 8 weeks) prior to administration of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Cholesterol Concentration of Chylomicron (Sf≥400) Fractions After a Cholesterol-Rich Test Meal | Immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours after test meal on Day 28 of each treatment period. | On each of 2 days prior to the last day of each treatment period, participants consumed 2 large eggs in the evening. On the morning of the final day of each treatment period, fasting participants were given a site-prepared, cholesterol-enriched milkshake that provided 1114 calories of total energy (\ 44% of calories from fat, \ 40% of calories from carbohydrate and \ 17% of calories from protein) and 504 mg of cholesterol. The milkshake was consumed over a 15-minute period. Plasma samples were collected immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours afterwards for isolation and analysis of lipoprotein fractions. The geometric mean concentration level was calculated using data obtained at all timepoints. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Cholesterol Concentration of Chylomicron-remnant (Sf 60-400) Subfractions After a Cholesterol-Rich Test Meal | Immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours after test meal on Day 28 of each treatment period. | On each of 2 days prior to the last day of each treatment period, participants consumed 2 large eggs in the evening. On the morning of the final day of each treatment period, fasting participants were given a site-prepared, cholesterol-enriched milkshake that provided 1114 calories of total energy (\ 44% of calories from fat, \ 40% of calories from carbohydrate and \ 17% of calories from protein) and 504 mg of cholesterol. The milkshake was consumed over a 15-minute period. Plasma samples were collected immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours afterwards for isolation and analysis of lipoprotein subfractions. The geometric mean concentration level was calculated using data obtained at all timepoints. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe→Placebo After a 2-week single- blind placebo run-in, participants will receive ezetimibe 10 mg once daily for 4 weeks and then receive placebo once daily for 4 weeks. | 28 |
| Placebo→ Ezetimibe After a 2-week single- blind placebo run-in, participants will receive placebo once daily for 4 weeks and then receive ezetimibe10 mg once daily for 4 weeks. | 30 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Ezetimibe→Placebo | Placebo→ Ezetimibe | Total |
|---|---|---|---|
| Age, Continuous | 51.0 years STANDARD_DEVIATION 8.84 | 48.4 years STANDARD_DEVIATION 9.48 | 49.7 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 22 Participants | 28 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 56 | 0 / 58 |
| serious Total, serious adverse events | 0 / 56 | 0 / 58 |
Outcome results
Primary
Total Cholesterol Concentration of Chylomicron (Sf≥400) Fractions After a Cholesterol-Rich Test Meal
On each of 2 days prior to the last day of each treatment period, participants consumed 2 large eggs in the evening. On the morning of the final day of each treatment period, fasting participants were given a site-prepared, cholesterol-enriched milkshake that provided 1114 calories of total energy (\ 44% of calories from fat, \ 40% of calories from carbohydrate and \ 17% of calories from protein) and 504 mg of cholesterol. The milkshake was consumed over a 15-minute period. Plasma samples were collected immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours afterwards for isolation and analysis of lipoprotein fractions. The geometric mean concentration level was calculated using data obtained at all timepoints.
Time frame: Immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours after test meal on Day 28 of each treatment period.
Population: Participants who received at least one dose of study drug and did not have any protocol violations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Ezetimibe | Total Cholesterol Concentration of Chylomicron (Sf≥400) Fractions After a Cholesterol-Rich Test Meal | 0.45 mg/dL |
| Placebo | Total Cholesterol Concentration of Chylomicron (Sf≥400) Fractions After a Cholesterol-Rich Test Meal | 0.50 mg/dL |
p-value: 0.24195% CI: [0.73, 1.08]ANOVA
Secondary
Total Cholesterol Concentration of Chylomicron-remnant (Sf 60-400) Subfractions After a Cholesterol-Rich Test Meal
On each of 2 days prior to the last day of each treatment period, participants consumed 2 large eggs in the evening. On the morning of the final day of each treatment period, fasting participants were given a site-prepared, cholesterol-enriched milkshake that provided 1114 calories of total energy (\ 44% of calories from fat, \ 40% of calories from carbohydrate and \ 17% of calories from protein) and 504 mg of cholesterol. The milkshake was consumed over a 15-minute period. Plasma samples were collected immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours afterwards for isolation and analysis of lipoprotein subfractions. The geometric mean concentration level was calculated using data obtained at all timepoints.
Time frame: Immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours after test meal on Day 28 of each treatment period.
Population: Participants who received at least one dose of study drug and did not have any protocol violations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Ezetimibe | Total Cholesterol Concentration of Chylomicron-remnant (Sf 60-400) Subfractions After a Cholesterol-Rich Test Meal | 4.87 mg/dL |
| Placebo | Total Cholesterol Concentration of Chylomicron-remnant (Sf 60-400) Subfractions After a Cholesterol-Rich Test Meal | 4.78 mg/dL |
p-value: 0.81295% CI: [0.87, 1.2]ANOVA