| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Study in patients with mixed dyslipidemia (type IIb) at risk of cardiovascular disease not adequately controlled by 40 mg simvastatin alone. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027763 |
| E.1.2 | Term | Mixed hyperlipidemia |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of adding 145 mg fenofibrate to ongoing 40 mg simvastatin therapy to reduce TG and LDL-C and increase HDL-C, in patients with mixed dyslipidemia (type IIb) at risk of cardiovascular disease not adequately controlled by 40 mg simvastatin alone. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the efficacy of adding 145 mg of fenofibrate to 40 mg simvastatin compared to 40 mg simvastatin monotherapy after 12 and 24 weeks of treatment on the following parameters: Non HDL-Cholesterol, Total Cholesterol, Apo AI, Apo B, LDL size at 12 weeks, hs CRP and fibrinogen.To compare the safety of adding 145 mg fenofibrate to 40 mg simvastatin therapy with 40 mg of simvastatin over 24 weeks of treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Either gender
2. >=18 and < 75 years
3. Presenting with CHD or CHD risk equivalent per NCEP ATPIII (excluding diabetes) in whom 10-year risk for CHD is > 20%
OR
with no CHD but multiple >= 2 risk factors
4. Having signed a written informed consent
5. Patient must be willing to observe the AHA Step I or similar Diet recommended throughout the study.
6. Presenting at inclusion (V1) with mixed (type IIb) dyslipidemia documented in the medical file and defined as follows on fasting lipid lab results:
· For patients not treated with lipid lowering drugs at the time of blood sampling:
- TG >= 2.28 mmol/L (>=200 mg/dL) and
- TC >= 6.72 mmol/L (>= 260 mg/dL) or LDL-C >= 3.88 mmol/L ( >= 150 mg/dL) or non-HDL-C >=4.65 mmol/L ( >=180 mg/dL)
· For patients treated with lipid lowering drugs at the time of blood sampling:- patients with CHD or CHD risk equivalent in whom 10-year risk for CHD is > 20%:
- TG >= 1.71 mmol/L ( >=150 mg/dL) and
- LDL-C >= 2.58 mmol/L ( >=100 mg/dL) or Non-HDL-C >= 3.36 mmol/L ( >= 130 mg/dL)
- patients with multiple >= 2 risk factors:
- TG >= 1.71 mmol/L ( >= 150 mg/dL) and
- LDL-C >= 3.36 mmol/L ( >= 130 mg/dL) or non-HDL-C >= 4.13 mmol/L ( >= 160 mg/dL)
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 40 mg simvastatin run-in phase and the results have to confirm the diagnosis of mixed dyslipidemia as defined above. |
|
| E.4 | Principal exclusion criteria |
1. Known hypersensitivity to fibrates or simvastatin or known photoallergic or phototoxic reactions under treatment with fibrates or ketoprofen or known allergic reactions caused by peanuts, peanuts 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 baseline blood sample. Fibrates must be stopped at least 6 weeks prior to baseline blood sample.
21. Treated with lipid-lowering drugs (statin, ezetimibe, fibrate, niacin…) other than simvastatin 40 mg. Patients receiving regular maintenance doses below 1g/day 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 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...) and delavirdine, verapamil, diltiazem, amiodarone and nefazodone,
24. Change during the run-in period in medications that could interfere with the lipid profile (i.e., thiazide diuretics, systemic beta-blockers, thyroid hormones, retinoids, hormone replacement therapy).
25. Treated with weight lowering drugs (orlistat, sibutramine...) within the last 4 weeks before baseline blood sample and/or surgery (gastroplasty...) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| % change in TG, HDL-C and LDL-C, from randomization to 12 weeks of treatment |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 17 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 32 |
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