| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Patients with type IIb dyslipidemia and features of the metabolic syndrome. | |
| MedDRA Classification |
| 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 demonstrate, in patients with type IIb dyslipidemia and features of the metabolic syndrome, the clinical advantage of 145mg NanoCrystal® fenofibrate over 10mg ezetimibe on plasma triglycerides (TG) and HDL-cholesterol (HDL-C) levels. | |
| E.2.2 | Secondary objectives of the trial | To compare the efficacy of 145mg NanoCrystal® fenofibrate, 10mg ezetimibe and combined therapy (145mg NanoCrystal® fenofibrate + 10mg ezetimibe) from baseline to 12 weeks treatment on Total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides, Non HDL-Cholesterol, LDL size, Remnant Like Particles Cholesterol (RLP-C), Apo AI, Apo AII, Apo B, hs CRP, Fasting plasma Glucose and Insulin, HOMA-IR.
To assess the safety of 145mg NanoCrystal® fenofibrate, 10mg ezetimibe and combined therapy after 12 weeks of treatment. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Patients will be selected for V1 based on the biological values (not older than 6 months) of LDL-C, HDL-C and TG in their medical files.
A patient will be eligible for study participation if he/she meets the following criteria at randomisation (V2):
1. Both genders, from 18 to 70 years old,
2. Presenting with type IIb dyslipidemia, as evidenced by:
• LDL-C >or= 160 mg/dL (>or= 4.15 mmol/L)
• TG >or= 150 mg/dL (>or= 1.7 mmol/L), and <or= 400 mg/dL (<or= 4.5 mmol/L)
3. In addition, they should have at least 2 of 4 following criteria, thus qualifying for the ATPIII/NCEP criteria for metabolic syndrome :
• Waist circumference: men >102 cm, women >88cm
• HDL cholesterol: men < 40 mg/dL (<1 mmol/L) and women <50 mg/dL (<1.3 mmol/L)
• Blood pressure ≥ 130 / ≥ 85 mm Hg
• Fasting glucose ≥ 110 mg/dL (≥ 6.1 mmol/L)
4. With negative pregnancy test and a reliable method of contraception in female of
child bearing potential
5. Having signed a written informed consent at inclusion (V1)
6. Patient must be willing to observe the Step I Diet recommended by the NCEP throughout the study. | |
| E.4 | Principal exclusion criteria | A patient will be excluded from the study if he/she meets any of the following criteria at V2:
1. Known hypersensitivity to fibrates or ezetimibe or known photoallergic or phototoxic reactions under treatment with fibrates or ketoprofen.
2. Women who are not surgically sterilized or not using adequate contraceptive precautions or not postmenopausal
3. Pregnant or lactating women
4. 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:
5. Type 1 or type 2 diabetes (fasting plasma glucose ≥ 7 mmol/L)
6. Current chronic pancreatitis or identified risk or known history of acute pancreatitis
7. Known cholelithiasis in absence of cholecystectomy
8. Known gastric or peptic ulcer or intestinal disease within the previous 3 months of randomisation capable of modifying the intestinal absorption of the drugs
9. Significant hepatic disease: AST and/or ALT > 2 times the upper normal limit (UNL)
10. Acute alcohol intoxication, known alcoholism
11. Past medical history of myositis, myopathy or rhabdomyolysis
12. Musculoskeletal disease with increased Creatine phosphokinase (CK) > 3 times UNL
13. Renal failure or renal dysfunction defined by serum creatinine levels > 135 µmol/L in males and >110 µmol/L in females
14. Known abnormal thyroid hormone levels, or high thyroid stimulating hormone (TSH) level
15. Uncontrolled hypertension (SBP > 180 mm Hg and/or DBP > 110 mm Hg)
16. History of coronary heart disease (CHD), CHD-equivalent disease, or CHD risk >20% as defined by NCEP ATP III criteria
17. Any other severe pathology such as cancer, mental illness, chronic respiratory insufficiency, etc…, which in the opinion of the investigator might pose a risk to the patient or confound the results of the study
18. Treated with anti-diabetic drug(s), Cyclosporin A, anticoagulants, protease inhibitors
19. Treated within the last 4 to 6 weeks before randomisation with lipid lowering drug
20. Treated within the last 4 to 6 weeks before randomisation and/or surgery with weight lowering drugs
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Percent change in TG and HDL-C from baseline to 12 weeks treatment between 145mg NanoCrystal® fenofibrate and 10mg ezetimibe. | |
| 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 | No |
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| 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 | No |
| E.8.2.3 | Other | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
