Patients with Primary Hypercholesterolaemia MedDRA version: 20.0 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Zenon Neo
Product Code: EXT1036A
Pharmaceutical Form: Tablet
INN or Proposed INN: EZETIMIBE
CAS Number: 163222-33-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrat
Sponsors
Sanofi-Aventis Groupe
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants with primary hypercholesterolemia and either at High (cardiovascular) CV risk or Very High CV risk not adequately controlled on statins for 6 weeks prior to the screening visit, without any other lipid-modifying therapy (LMT), in respect to LDL-cholesterol, based on blood samples taken at V1 (screening visit): - Run-in criteria: High CV risk patients [LDL C =100 mg/dL (2.6 mmol/L) and =190 mg/dL (4.9 mmol/L)] with a stable daily dose of rosuvastatin 10 mg. High CV risk patients [LDL C =120 mg/dL (3.1 mmol/L) and =190 mg/dL (4.9 mmol/L)] with a stable daily dose of simvastatin 80 mg or atorvastatin 40 mg. OR Very High CV risk patients [LDL-C =70 mg/dL (1.8 mmol/L) and =160 mg/dL (4.1 mmol/L)] with a stable daily dose of rosuvastatin 20 mg. Very High CV risk patients [LDL-C =90 mg/dL (2.3 mmol/L) and =160 mg/dL (4.1 mmol/L)] with a stable daily dose of atorvastatin 80 mg. - Randomization criteria: Patient not adequately controlled based on sample taken at V3 (qualifying visit, Week-1), despite stabilized dose of rosuvastatin therapy: High CV risk patients [LDL-Cholesterol =100 mg/dL (2.6 mmol/L) and = 190 mg/dL (4.9 mol/L)]; Very High CV risk patients [LDL-Cholesterol = 70 mg/dL(1.8 mmol/L) and =160 mg/dL (4.1 mmol/L)]. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 937 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 379
Exclusion criteria
Exclusion criteria: - Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping). - Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina, myocardial revascularization (percutaneous coronary intervention [PCI], coronary artery bypass graft surgery [CABG]), transient ischemic attack (TIA), or stroke, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease. - Hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg). - History of severe congestive heart failure (New York Heart Association Class IIIb or IV) within the past 12 months. - Participants not previously instructed on a cholesterol-lowering diet prior to the screening visit. - Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins according to investigator's medical judgement.. - Poorly controlled (HbA1c >9%) or newly diagnosed (within 3 months prior to screening) diabetes mellitus. - Use of systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to screening visit. - Use of hormone replacement therapy or oral contraceptives unless regimen stable in the past 6 weeks prior to the screening visit and no plans to change the regimen during the study. - Use of red yeast rice products for at least 6 weeks prior to screening visit or plan to take these products before the end of treatment (EOT) visit. - History of cancer within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer. - Current myopathy - A history of statin-induced myopathy or rhabdomyolysis. - All contraindications to the active comparator (rosuvastatin) and background therapies or warning/precaution of use (when appropriate) as displayed in the respective National Product Labeling. - Known history of hypersensitivity reaction to statins and/or ezetimibe. -Current active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x upper limif of normal (ULN). - Asian participants for the VHR group (rosuvastatin 40 mg being contra- indicated). - Severe renal impairment for HR and moderate renal impairment for VHR participants.D
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority of 2 fixed dose combinations (FDCs) ezetimibe/rosuvastatin compared to 2 up-titrated doses of rosuvastatin, and a third FDC ezetimibe/rosuvastatin compared to the same dose of rosuvastatin monotherapy, in the reduction of low-density lipoprotein cholesterol (LDL-C).;Secondary Objective: - To compare the 2 FDCs ezetimibe/rosuvastatin to relative run-in treatments (i.e.,same doses of rosuvastatin), in terms of reduction of LDL-C. - To evaluate the proportion of patients who attain their LDL-C goal. - To evaluate the effect of all FDCs on other lipid parameters. - To evaluate the safety of all FDCs.;Primary end point(s): Percent change in calculated low-density lipoprotein cholesterol (LDL-C) value;Timepoint(s) of evaluation of this end point: From baseline to Week 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in calculated LDL-C : In participants randomized to the Ezetimibe/Rosuvastatin dose 1 and dose 2 arms: percent change in calculated LDL-C from baseline to Week 6 2. Lipid goal levels : Percentage of participants achieving lipid goal levels defined as: - Calculated LDL-C <100 mg/dL (2.6 mmol/L) at Week 6 for HR participants - Calculated LDL-C <70 mg/dL (1.8 mmol/L) at week 6 for VHR participants 3. Change in total cholesterol (Total-C) plasma levels : Percent change in Total-C from baseline to Week 6 4. Change in high-density lipoprotein cholesterol (HDL-C) : Percent change in HDL-C from baseline to Week 6 5. Change in triglycerides (TG) : Percent change in TG plasma levels from baseline to Week 6;Timepoint(s) of evaluation of this end point: 1. From baseline to Week 6 2. At Week 6 3. From baseline to Week 6 4. From baseline to Week 6 5. From baseline to Week 6 | — |
Countries
Bulgaria, Czech Republic, Italy, Mexico, Poland, Russian Federation, Slovakia, Ukraine
Contacts
Public Contactwww.sanofi.cz
sanofi-aventis, s.r.o.
Outcome results
None listed