A Study of SCH 58235 (Ezetimibe) When Added to Ongoing Therapy With a Statin in Participants With Primary Hypercholesterolemia, Known Coronary Heart Disease, or Multiple Cardiovascular Risk Factors (P02173)
- Conditions
- Primary Hypercholesterolemia
- Interventions
- Registration Number
- NCT03882905
- Lead Sponsor
- Organon and Co
- Brief Summary
This is a study to evaluate the lipid-altering efficacy, safety, and tolerability of ezetimibe when added to ongoing therapy with an 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) in participants with primary hypercholesterolemia, multiple cardiovascular risk factors, or known coronary heart disease (CHD) or CHD-equivalent disease. The statin and dose in use by the participant at screening will be maintained at the same dose for the 8-week treatment phase of the study. Following the treatment, there will be a 6-week cholesterol reversibility phase to determine the rebound effect on cholesterol after ezetimibe is discontinued, but the participant is still on their statin therapy. The primary hypothesis is that the addition of ezetimibe 10 mg/day to ongoing statin monotherapy will result in a further reduction in low-density lipoprotein-cholesterol (LDL-C) compared with placebo.
The protocol was amended to include an extension for participants who complete the base study. The extension will evaluate the safety and tolerability of concomitant treatment of simvastatin with ezetimibe10 mg/day over a 1-year period. All participants in the extension will be converted from current statin to an equivalent dose of simvastatin for 6 weeks. Participants then will be randomly assigned to receive simvastatin coadministered with either with Ezetimibe 10 mg daily or matching placebo for the reminder of study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 769
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo: Base Study Statin Placebo for ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks. Ezetimibe: Base Study Statin 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks. Ezetimibe: Extension Ezetimibe 10-mg tablet, oral taken once daily concomitantly with simvastatin for 48 weeks. Ezetimibe: Extension Simivastatin 10-mg tablet, oral taken once daily concomitantly with simvastatin for 48 weeks. Placebo: Base Study Placebo Placebo for ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks. Placebo: Extension Placebo Placebo for ezetimibe tablet, oral taken once daily concomitantly with simvastatin for 48 weeks. Ezetimibe: Base Study Ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks. Placebo: Extension Simivastatin Placebo for ezetimibe tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.
- Primary Outcome Measures
Name Time Method Percentage Participants with Consecutive Elevations ≥3 x Upper Limit of Normal (ULN) in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT): Extension up to 48 weeks (Extension) Percentage Change from Baseline in LDL-C: Base Study Baseline and Week 8 of Base Study
- Secondary Outcome Measures
Name Time Method Percentage Change from Baseline in Non-HDL-C: Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in Apolipoprotein A-II (Apo A-II) : Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) : Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in LDL-C:HDL-C Ratio: Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in Triglycerides (TG): Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in Apolipoprotein B (apoB) : Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in Apolipoprotein A-I (Apo A-I) : Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in Total-C:HDL-C Ratio: Base Study Baseline and Week 8 of Base Study Percentage Change from Baseline in LDL-C: Extension Baseline (Week 6) and Week 18 of Extension Percentage of Participants Achieving LDL-C National Cholesterol Education Program (NCEP) Adult Treatment Program II (ATP II) Target Levels: Base Study Week 8 of Base Study Percentage Change from Baseline in Total Cholesterol (TC) : Base Study Baseline and Week 8 of Base Study Change from Baseline in C-reactive Protein (CRP): Base Study Baseline and Week 8 of Base Study