Metabolic syndrome as defined by the ATP III criteria MedDRA version: 9.1 Level: LLT Classification code 10052066 Term: Metabolic syndrome
Conditions
Interventions
Trade Name: Zocor
Pharmaceutical Form: Tablet
INN or Proposed INN: SIMVASTATIN
CAS Number: 79902639
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Pharmaceutic
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. All patients should fulfill the diagnostic criterium of abdominal adiposity according to the modified 2005 AHA/NHLBI Scientific Statement Males: waist circumference =102 cm (=40 in) Note: For male Asian Americans (as reported by the patient), waist circumference =90 cm (=35 in) Females: waist circumference (=35 in) Note: For female Asian Americans (as reported by the patient), waist circumference =80 cm (=31 in) 2. Patient has a diagnosis of metabolic syndrome according to the modified 2005 AHA/NHLBI Scientific Statement which include in addition to abdominal adiposity 2 of the following 4 risk factors. i) Triglycerides (TG) TG =150 mg/dL (=1.7 mmol/L) ii) HDL Cholesterol Males: HDL-C =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Patient weighs (>159 kg). 2.Patient has a hypersensitivity or intolerance to ezetimibe or simvastatin or any component of these medications. 3.Patient consumes more than 14 alcoholic drinks per week. 4.Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent. 5.Patient has smoked 10 packyears 6.Patient has exclusionary laboratory values at Visit 1 as listed in the table below: liver transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST])> 1.5 X ULN with no active liver disease Glucose > 7.0 mmol/L (126 mg/dL) Creatine kinase (CK) > 2 X ULN Albumin:creatinine ratio >34 TSH 5.0 mcIU/mL 7.Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate. 8.Patient has congestive heart failure. 9.Patient has atherosclerotic vascular disease. 10.Patient has acute or chronic coronary heart disease. 11.Patient has a history of pre-eclampsia 160 mm Hg or diastolic >100 mm Hg at Visit 1(Week -4/-3). 15.Patient has estimated glomerular filtration rate (eGFR) 126 mg/dL. 19.Patient is known to be HIV positive. 20.Patient has a history of malignancy = 5 years prior to signing informed consent, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer. 21.Patient is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence. 22.Patient has a history of mental instability or major psychiatric illness not adequately controlled and stable on pharmacotherapy. 23.Patient has Raynauds Syndrome. 24.Patient has significant aortic coarctation. 25.Patient has significant deformity of fingers of either hand prohibiting use of the same digit on both hands for ENDOPAT. 26.Patient has had a mastectomy or is going to have one during the study period. 27.Patient has a history of upper extremity thrombosis 28.Patient is currently taking any antihypertensive or vasoactive medications. This includes standard antihypertensive drug therapies and nitrates. 29.Patient is currently taking any potent inhibitor of cytochrome P450 3A4 (CYP3A4), such as: itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, or nefazodone. 30.Patient is currently taking therapies that could increase the risk of myopathy, such as: verapamil, amiodarone, or trandolapril/verapamil. 31.Patient is currently taking cyclosporine, dan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare postprandial endothelial function (pre-meal minus post-meal) measured by brachial artery flow-mediated dilation (FMD) after 6 weeks of treatment with ezetimibe/simvastatin (10 mg/10 mg) combination tablet versus simvastatin 80 mg tablet.;Secondary Objective: 1. To compare postprandial endothelial function (pre-meal minus post-meal) measured by finger plethysmography (ENDOPAT) after 6 weeks of treatment with ezetimibe/simvastatin (10 mg/10 mg) combination tablet versus simvastatin 80 mg tablet. 2. To compare pre-meal endothelial function assessed by brachial artery flow-mediated dilation (FMD) after 6 weeks of treatment with ezetimibe/simvastatin (10 mg/10 mg) combination tablet versus simvastatin 80 mg tablet. 3. To compare pre-meal endothelial function assessed by finger plethysmography (ENDOPAT) after 6 weeks of treatment with ezetimibe/simvastatin (10 mg/10 mg) combination tablet versus simvastatin 80 mg tablet.;Primary end point(s): Efficacy Endpoints The primary efficacy endpoint is the delta between pre-meal and post-meal FMD (FMD pre-meal minus FMD 4 hours post-meal) following 6 weeks of treatment with simvastatin 10 mg combined with ezetimibe 10 mg or simvastatin 80 mg monotherapy. Secondary efficacy endpoint include the delta of pre-meal and post-meal (pre-meal minus post-meal) of finger plethysmography (ENDOPAT) after 6 weeks of treatment. In addition, a within group comparison will be made from pre to post meal changes in FMD and ENDOPAT in both groups. The pre-meal FMD and ENDOPAT measurement after 6 weeks of treatment, pre-meal and post-meal, AUC and AUIC of lipids, apolipoproteins, and lipoprotein compositional changes (e.g., LDL-C, total cholesterol (TC), TG, free fatty acids, HDL-C, non-HDL-C, Apo A-1, Apo B48 and B100, inflammatory markers, oxysterols, and phytosterols) will also be examined. Safety Endpoints Safety will be assessed primarily by clinical and statistical review of all safety parameters, includin | — |
Countries
Netherlands, Spain
Outcome results
None listed