Hypercholesterolemia, Coronary Arteriosclerosis
Conditions
Brief summary
This study is being conducted to compare the efficacy, safety, and tolerability of ezetimibe 10 mg coadministered with atorvastatin 10 mg versus atorvastatin 10 mg in Indonesian population with primary hypercholesterolemia.
Interventions
DRUGEzetimibe
10 mg ezetimibe, orally, daily for 6 weeks, added to ongoing treatment with 10 mg atorvastatin
DRUGPlacebo
10 mg/day matching placebo to ezetimibe, orally, daily for 6 weeks, added to ongoing 10 mg atorvastatin
10 mg/day atorvastatin, orally, (ongoing treatment in participants)
Sponsors
PT. Schering-Plough. Tbk Indonesia
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have an LDL-C concentration \>= 3.3 mmol/L (130 mg/dL) to \<= 4.9 mmol/L (190 mg/dL) using the Freidewald calculation. * Participants must have triglyceride concentrations of \< 3.99 mmol/L (350 mg/dL). * Participants must have two or more coronary heart disease risk factors listed below: * Current cigarette smoking * Hypertension (BP \>= 140/90 mmHg or on antihypertensive medication) * Low HDL cholesterol (\< 40 mg/dL) * Family history of premature CHD (CHD in male first degree relative \< 55 years; CHD in female first degree relative \< 65 years) * Age (Men \>= 45 years; women \>= 55 years) * Participant must be currently taking atorvastatin 10 mg daily and by history has taken 80% of daily doses for the 6 weeks prior to participating. * Participants must have liver transaminases (ALT, AST) \< 50% above the upper limit of normal, with no active liver disease, and CK \< 50% above the upper limit of normal. * Participants must have maintained a cholesterol lowering diet, exercise program, and stable weight for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study. * Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study.
Exclusion criteria
* Participants who meet any of the following criteria will be excluded: * Body mass index (BMI = weight \[kg\]/height\*\*2\[m\]) is \>= 30 Kg/m\*\*2. * Consume \> 14 alcoholic drinks per week. * Women who are pregnant or nursing. * Congestive heart failure defined by NYHA as Class III or IV. * Uncontrolled cardiac arrhythmia. * Coronary heart disease (CHD). * Unstable or severe peripheral artery disease within 3 months of participating * Uncontrolled hypertension (treated or untreated) with systolic blood pressure \> 160 mm Hg or diastolic \> 100 mm Hg. * Type I or Type II diabetes mellitus. * Secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism. * Impaired renal function (creatinine \> 2.0 mg/dL) or nephrotic syndrome. * Known HIV positive. * Cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas). * History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy. * Participants who are on any of the following concomitant medications: * Participants who are on medications that are potent inhibitors of CYP3A4, including cyclosporine, systemic itraconazole, fluconazole, and ketoconazole, erythromycin or clarithromycin, nefazodone, mibefradil, protease inhibitors and large amounts of grapefruit juice (\> 1 quart/day). * Participants who are on lipid-lowering agents (other atorvastatin): niacin (\> 200 mg/day) * Participants who are on over the counter lipid lowering agents such as fish oils, garlic and cholestin * Participants who are on oral corticosteroids, unless used as replacement therapy for pituitary/adrenal disease and the subject is on a stable regimen for at least 6 weeks. * Participants who are currently using psyllium, other fiber-based laxatives, and/or any other OTC therapy known to affect serum lipid levels (phytosterol margarine), and have not been on a stable regimen for at least 5 weeks and who do not agree to remain on this regimen throughout the study. * Participant who are currently using orlistat or sibutramine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Baseline and 6 weeks | 12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - \[HDL-C + TG/5\]) before and after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve the Target LDL-C Concentration of < 3.3 mmol/L (130 mg/dL) | 6 weeks post treatment | 12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - \[HDL-C + TG/5\] after treatment for 6 weeks. |
| High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | 6 weeks post treatment | 12-hour fasting blood samples were collected in participants and the high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol was measured with the basic lipid panel test. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe 10 mg Participants treated with 10 mg/day ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin. | 10 |
| Placebo 10 mg Participants treated with 10 mg/day matching placebo to ezetimibe added to an ongoing treatment of 10 mg/day atorvastatin. | 12 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Noncompliance with the protocol | 1 | 0 |
| Overall Study | Subject did not wish to continue | 1 | 0 |
Baseline characteristics
| Characteristic | Ezetimibe 10 mg | Placebo 10 mg | Total |
|---|---|---|---|
| Age, Continuous | 57.4 Years STANDARD_DEVIATION 12.1 | 52.2 Years STANDARD_DEVIATION 10.4 | 54.5 Years STANDARD_DEVIATION 11.3 |
| Age, Customized 18 to <65 years | 7 Participants | 11 Participants | 18 Participants |
| Age, Customized 65 or older | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Indonesia | 10 participants | 12 participants | 22 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 10 | 3 / 12 |
| serious Total, serious adverse events | 1 / 10 | 0 / 12 |
Outcome results
Primary
Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg
12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - \[HDL-C + TG/5\]) before and after treatment.
Time frame: Baseline and 6 weeks
Population: Participants who completed the study.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ezetimibe 10 mg | Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Baseline | 148.125 mg/dL |
| Ezetimibe 10 mg | Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | 6 weeks post treatment | 106.000 mg/dL |
| Placebo 10 mg | Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Baseline | 151.083 mg/dL |
| Placebo 10 mg | Low Density Lipoprotein-cholesterol (LDL-C) at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | 6 weeks post treatment | 108.273 mg/dL |
Secondary
High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg
12-hour fasting blood samples were collected in participants and the high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol was measured with the basic lipid panel test.
Time frame: 6 weeks post treatment
Population: Participants who completed the study.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ezetimibe 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | HDL-C at baseline | 53.250 mg/dL |
| Ezetimibe 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | HDL-C at 6 weeks | 52.625 mg/dL |
| Ezetimibe 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Total Cholesterol at baseline | 219.125 mg/dL |
| Ezetimibe 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Total Cholesterol at 6 weeks | 156.375 mg/dL |
| Ezetimibe 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Triglycerides at baseline | 139.500 mg/dL |
| Ezetimibe 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Triglycerides at 6 weeks | 115.250 mg/dL |
| Placebo 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Triglycerides at baseline | 131.667 mg/dL |
| Placebo 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | HDL-C at baseline | 57.667 mg/dL |
| Placebo 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Total Cholesterol at 6 weeks | 185.667 mg/dL |
| Placebo 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | HDL-C at 6 weeks | 53.500 mg/dL |
| Placebo 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Triglycerides at 6 weeks | 120.250 mg/dL |
| Placebo 10 mg | High Density Lipoprotein-cholesterol (HDL-C), Total Cholesterol and Triglycerides at Baseline and After 6 Weeks of Treatment With Ezetimibe 10 mg Added to Atorvastatin 10 mg Versus Placebo Added to Atorvastatin 10 mg | Total Cholesterol at baseline | 226.000 mg/dL |
Secondary
Number of Participants Who Achieve the Target LDL-C Concentration of < 3.3 mmol/L (130 mg/dL)
12-hour fasting blood samples were collected in participants to measure high density lipoprotein-cholesterol (HDL-C), triglycerides and total cholesterol. LDL-C was measured using Friedewald calculation (LDL-C = Total C - \[HDL-C + TG/5\] after treatment for 6 weeks.
Time frame: 6 weeks post treatment
Population: Participants who completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe 10 mg | Number of Participants Who Achieve the Target LDL-C Concentration of < 3.3 mmol/L (130 mg/dL) | 7 Participants |
| Placebo 10 mg | Number of Participants Who Achieve the Target LDL-C Concentration of < 3.3 mmol/L (130 mg/dL) | 8 Participants |