Primary Hypercholesterolemia MedDRA version: 14.1 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Ezetrol 10mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: EZETIMIBE
CAS Number: 163222-33-1
Current Sponsor code: MK-0653
Concentration unit: mg milligram(s)
Concentration type
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women =18 and 20% (as determined by the Framingham calculation) - High-risk patients with cardiovascular disease (CVD)* including patients with established coronary and other atherosclerotic vascular disease Patients will be eligible to continue to Visit 5 (Week 5) if they meet the following criteria: 12. Patient has completed the 5 week atorvastatin 10 mg run-in period. 13. Patient has at least 75% compliance with run-in medication during the active run-in period (determined by pill count) or, if patients are <75% compliance with run-in medication, they w
Exclusion criteria
Exclusion criteria: 1. Patient is Asian. 2. Patient has hypersensitivity or intolerance to ezetimibe, atorvastatin, rosuvastatin, or any component of these medications, or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin. 3. Patient routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week). * 4. Female patient who is pregnant or lactating. 5. Patient has been treated with any other investigational drug within 30 days of Visit 1 (Week -6). 6. Patient has any condition or situation which, in the opinion of the investigator, might have posed a risk to the patient or interfere with participation in the study. Prohibited Medical Conditions 7. Patient has congestive heart failure defined by NYHA (New York Heart Association) Class III or IV. 8. Patient has had a myocardial infarction, coronary artery bypass surgery, angioplasty, or acute coronary syndrome within 3 months prior to Visit 1. 9. Patient has uncontrolled cardiac arrhythmias or recent significant changes in the patient’s electrocardiogram (ECG) as taken within 6 months prior to Visit 1. 10. Patient has homozygous familial hypercholesterolemia or has undergone LDL-C apheresis. 11. Patient has had a partial ileal bypass, gastric bypass, or other significant intestinal malabsorption. 12. Patient has uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mmHg or diastolic >100 mmHg at Visit 2 (Week –5). Investigators are encouraged to maximize blood pressure control according to current guidelines. 13. Patient has estimated glomerular filtration rate (eGFR) 5 cups (1.2 L) of grapefruit juice per day. 23. Patient has
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: In patients with primary hypercholesterolemia and high cardiovascular risk with LDL-C =100 mg/dL (2.59 mmol/L) and =160 mg/dL (4.14 mmol/L), to evaluate: 1) at the end of Phase II, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 20 mg compared to atorvastatin 40 mg among patients who are not adequately controlled with atorvastatin 10 mg prior to randomization and not adequately controlled with atorvastatin 20 mg during Phase I 2) at the end of Phase II, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 20 mg compared to rosuvastatin 20 mg among patients who are not adequately controlled with atorvastatin 10 mg prior to randomization and who are not adequately controlled with rosuvastatin 10 mg during Phase I Please refer to protocol for the rest of the secondary objectives;Primary end point(s): Percent change from baseline in LDL-C.;Timepoint(s) of evaluation of this end point: The primary end point is the comparison of the change in LDL-C from baseline to the end of Phase I (Visit 6) after 6 weeks double-blinded treatment with EZ 10mg + Atorva 10 mg, compared to Atorva 20 mg, or Rosuva 10 mg.;Main Objective: In patients with primary hypercholesterolemia and high cardiovascular risk with LDL-C =100 mg/dL (2.59 mmol/L) and =160 mg/dL (4.14 mmol/L), to evaluate: 1) at the end of Phase I, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 10 mg compared to atorvastatin 20 mg among patients who are not adequately controlled with atorvastatin 10 mg prior to randomization. 2) at the end of Phase I, the additional LDL-C percentage reduction by switching to coadministered ezetimibe 10 mg + atorvastatin 10 mg compared to rosuvastatin 10 mg among patients who are not adequately controlled with atorvastatin 10 mg prior to randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: 1) Additional percent change from baseline in LDL-C at the end of Phase II; comparison of EZ 10mg + Atorva 20 mg, to Atorva 40 mg, or Rosuva 20 mg 2) Percent of patients reaching LDL-C <100 mg/dL (2.59 mmol/L) at the end of Phase I 3) Percent of patients reaching LDL-C <100 mg/dL (2.59 mmol/L) at the end of Phase II. 4) Percent changes from baseline in TC, TG, HDL-C, Apo B, Apo A-I, non-HDL-C, TC/HDL-C ratio, LDL-C/HDL-C ratio, Apo B/Apo A-I ratio, non-HDL-C/HDL-C ratio and hs-CRP at the end of Phase I. 5) Additional percent changes from baseline in TC, TG, HDL-C, Apo B, Apo A-I, non-HDL-C, TC/HDL-C ratio, LDL-C/HDL-C ratio, Apo B/Apo A-I ratio, non-HDL-C/HDL-C ratio and hs-CRP at the end of Phase II. 6) Safety and tolerability of EZ 10 mg + Atorva 10 mg versus Atorva 20 mg and Rosuva 10 mg and the safety of EZ 10 mg + Atorva 20 mg versus Atorva 40 mg and Rosuva 20 mg. ;Timepoint(s) of evaluation of this end point: Secondary end points will be evaluated at the end of Phase I (Visit 6) following 6 weeks double-blinded treatment with either EZ 10mg + Atorva 10 mg, or Atorva 20 mg, or Rosouva 10 mg, and Phase II (Visit 8), following another 6 weeks double-blinded treatment with either EZ 10mg + Atorva 20 mg, or Atorva 40 mg, or Rosuva 20 mg. | — |
Countries
Argentina, Belgium, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Lithuania, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed