A Phase 3, Double-Blind Efficacy and Safety Study of Ezetimibe (SCH 58235) 10 mg in Addition to Atorvastatin Compared to Placebo in Subjects With Primary Hypercholesterolemia (Protocol P00692)
Overview
- Phase
- Phase 3
- Intervention
- Atorvastatin 10 mg
- Conditions
- Hypercholesterolemia
- Sponsor
- Organon and Co
- Enrollment
- 628
- Primary Endpoint
- Percent Change from Baseline at Week 12 of Plasma Low Density Lipoprotein Cholesterol (LDL-C)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled, balanced-parallel-group, efficacy and safety trial of ezetimibe coadministered with atorvastatin in adult participants with primary hypercholesterolemia. The primary hypothesis is that the coadministration of ezetimibe 10 mg/day with atorvastatin (pooled across all doses: 10 mg, 20 mg, 40 mg, 80 mg) will result in a significantly greater reduction in direct low density lipoprotein-cholesterol (LDL-C) when compared with atorvastatin (pooled across all doses: 10 mg, 20 mg, 40 mg, 80 mg) alone and ezetimibe 10 mg alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •If female, is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP), or is a WOCBP who has used a contraceptive consistent with local regulations.
- •Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene regimen during the study period.
- •Primary hypercholesterolemic participants with a plasma LDL-Cholesterol ≥145 mg/dL (3.75 mmol/L) and ≤250 mg/dL (6.48 mmol/L) and plasma triglyceride ≤350 mg/dL (3.99 mmol/L) after adequate drug washout
- •Must be willing to observe the National Cholesterol Education Program (NCEP) Step I diet as determined by a Ratio of Ingested Saturated fat and Cholesterol to Calories (RISCC) score not greater than 24 throughout this study. Ability to complete Diet Diaries needs to be demonstrated.
Exclusion Criteria
- •Has a history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
- •Underlying disease likely to limit life span to less than 1 year.
- •Participants with hypercholesterolemia in whom withholding of approved lipid-lowering therapy would be inappropriate.
- •Have previously been randomized in any of the studies evaluating Ezetimibe (SCH 58235).
- •Known hypersensitivity or any contraindication to atorvastatin (LIPITOR®).
- •Pregnant or lactating women.
- •Congestive heart failure New York Heart Association (NYHA) Class III or IV.
- •Uncontrolled cardiac arrhythmias.
- •Myocardial infarction, coronary bypass surgery or angioplasty within 6 months of study entry.
- •Unstable or severe peripheral artery disease within 3 months of study entry.
Arms & Interventions
Atorvastatin 10 mg
Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 10 mg
Ezetimibe 10 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Ezetimibe 10 mg
Placebo
Placebo is to be taken orally once a day (QD) in the morning for 12 consecutive weeks.
Intervention: Placebo
Ezetimibe 10 mg + Atorvastatin 10 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Ezetimibe 10 mg
Ezetimibe 10 mg + Atorvastatin 10 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 10 mg
Atorvastatin 20 mg
Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 20 mg
Ezetimibe 10 mg + Atorvastatin 20 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Ezetimibe 10 mg
Ezetimibe 10 mg + Atorvastatin 20 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 20 mg
Atorvastatin 40 mg
Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 40 mg
Ezetimibe 10 mg + Atorvastatin 40 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Ezetimibe 10 mg
Ezetimibe 10 mg + Atorvastatin 40 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 40 mg
Atorvastatin 80 mg
Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 80 mg
Ezetimibe 10 mg + Atorvastatin 80 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Ezetimibe 10 mg
Ezetimibe 10 mg + Atorvastatin 80 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Intervention: Atorvastatin 80 mg
Outcomes
Primary Outcomes
Percent Change from Baseline at Week 12 of Plasma Low Density Lipoprotein Cholesterol (LDL-C)
Time Frame: Baseline and Week 12
Plasma LDL-C determined following a standard ultracentrifugation / precipitation (quantification) procedure (direct LDL-C). Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Secondary Outcomes
- Percent Change from Baseline at Week 12 for High Density-Lipoprotein 2-Cholesterol (HDL2-C)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for High Density-Lipoprotein 3-Cholesterol (HDL3-C)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Calculated Low Density Lipoprotein-Cholesterol (LDL-C)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Non-High Density-Lipoprotein-Cholesterol (Non-HDL-C)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Total Cholesterol (TC)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Apolipoprotein B (Apo B)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for High Density-Lipoprotein-Cholesterol (HDL-C)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Direct Total Cholesterol/High Density-Lipoprotein 3-Cholesterol (TC/HDL-C) Ratio(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Triglycerides (TG)(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Direct Low Density-Lipoprotein 3-Cholesterol/High Density-Lipoprotein 3-Cholesterol (LDL-C/HDL-C) Ratio(Baseline and Week 12)
- Percent Change from Baseline at Week 12 for Lipoprotein (a) (Lp[a])(Baseline and Week 12)
- The Percentage of Participants Achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP II) Target Goal for Direct Low Density Lipoprotein-Cholesterol (LDL-C)(Week 12)
- Percent Change from Baseline at Week 12 for Apolipoprotein A-I (Apo A-I),(Baseline and Week 12)