Study in patients with mixed dyslipidemia at risk of cardiovascular disease not adequately controlled by 20 mg simvastatin alone
Conditions
Interventions
Product Name: simvastatin 20 mg
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: simvastatin
CAS Number: 79902-63-9
Current Sponsor code: N/A
Other descriptive name: N/A
Sponsors
FOURNIER Laboratories Ireland Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Either gender 2. = 18 and 20%: - TG = 150 mg/dL (= 1.71 mmol/L) and - LDL-C = 100 mg/dL (= 2.58 mmol/L) or Non-HDL-C = 130 mg/dL (= 3.36 mmol/L) - Patients with multiple = 2 risk factors: - TG = 150 mg/dL (= 1.71 mmol/L) - LDL-C =130 mg/dL (= 3.36 mmol/L) or non-HDL-C = 160 mg/dL (= 4.13 mmol/L) If there are no fasting lipid lab results available in the patient's medical file at V1, a fasting lipid lab test must be performed in a local lab before entering the patient in the 20 mg simvastatin run-in phase and the results have to confirm the diagnosis of mixed dyslipidemia as defined above. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to fibrates or simvastatin or known photoallergic or phototoxic reactions undertreatment with fibrates or ketoprofen or known allergic reactions caused by peanuts, peanut oil and soy lecithin 2. Pregnant or lactating women 3. Unable or unwilling to comply with the protocol and the recommended diet 4. Likely to withdraw from the study before its completion 5. Having received an investigational drug or vaccine in the last 30 days before date of inclusion, or still participating in such a trial at V1 Associated diseases or conditions: 6. Known type 1 or type 2 diabetes 7. Known active or chronic hepatobiliary or liver diseases 8. Known cholelithiasis (except in case of cholecystectomy) 9. Current chronic pancreatitis or identified risk or past history of acute pancreatitis 10. Known current alcoholism or alcohol intake greater than 21 units per week 11. Medical history of myositis, myopathy or rhabdomyolysis 12. Known abnormal thyroid hormone levels (clinically euthyroid patients on stable replacement doses of thyroid hormone are eligible for inclusion) 13. Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins 14. Known renal failure or renal dysfunction 15. Congestive heart failure NYHA Class III or IV (class III marked limitation of physical activity, class IV inability to carry out any physical activity without discomfort) 16. Uncontrolled cardiac arrhythmias 17. Myocardial infarction, coronary bypass surgery or angioplasty within 3 months of inclusion in the study 18. Unstable or severe peripheral artery disease within 3 months of inclusion in the study 19. Unstable angina pectoris within 3 months of inclusion in the study 20. Any other severe pathology such as cancer or mental illness or degenerative disease that would limit study evaluation or participation Concomitant medications: For prohibited concomitant medication ongoing at V1 other than lipid-lowering drugs, treatment must be stopped, if clinically appropriate. If not clinically appropriate, the patient should not be included in the study. Treatment with lipid-lowering drugs other than fibrates must be stopped at least 4 weeks prior to first baseline blood sample. Fibrates must be stopped at least 6 weeks prior to first baseline blood sample. 21. Treated with lipid-lowering drugs (statin, ezetimibe, fibrate, niacin…) other than simvastatin 20 mg. Patients receiving regular maintenance doses of OTC lipid lowering medications (e.g. fish oils, omega-3 fatty acids supplements…) or OTC products (e.g. psyllium, fiber-based preparations and phytosterols) can be enrolled provided they are on stable dose for at least 4 weeks before randomization and agree to take the same preparation at an unchanged dose for the study duration. 22. Treated with cyclosporin A, anti-vitamin K, long term systemic corticosteroids (unless the corticosteroids are for replacement therapy to treat pituitary adrenal disease and patients were treated with a stable regimen for at least 4 weeks before first baseline blood sample), 23. Treated with CYTP3A4 inhibitors or products with known drug interaction with simvastatin such as antifungal azoles (itraconazole, ketoconazole…), macrolide antibiotics (erythromycin, clarithromycin, telithromycin), HIV protease inhibitors (indinavir, ritonavir, saquinavir...), verapamil, diltiazem, amiodarone and nefazodone, 24. Change during the run-in period in medications that could interfere with the lipid profile
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy, in patients with mixed dyslipidemia (type IIb) not adequately controlled by 20 mg simvastatin alone, of adding 145 mg of fenofibrate to 20 mg simvastatin compared to doubling the dose of simvastatin to reduce TG and increase HDL-C without loosing efficacy on reducing LDL-C, after 12 weeks of treatment.;Secondary Objective: To evaluate the efficacy of adding 145 mg of fenofibrate to 40 mg simvastatin compared to 40 mg simvastatin monotherapy to reduce TG and LDL-C and increase HDL-C. To evaluate the efficacy of adding 145 mg of fenofibrate to 20 then 40 mg simvastatin compared to 40 mg simvastatin monotherapy from baseline to 12 and 24 weeks of treatment on the following parameters: Non HDL-Cholesterol, Total Cholesterol, LDL size, Apo AI, Apo B, hs CRP and fibrinogen. To compare the safety of adding 145 mg fenofibrate to 20 then 40 mg simvastatin therapy with 40 mg of simvastatin over 12 and 24 weeks of treatment. To evaluate the long-term, up to one year, safety and efficacy, of combining 145 mg fenofibrate with 20 or 40 mg simvastatin.;Primary end point(s): % change in TG, HDL-C and LDL-C, from randomization to 12 weeks of treatment | — |
Countries
Czech Republic, Germany, Hungary
Outcome results
None listed