Primary hypercholesterolemia or mixed dyslipidemia MedDRA version: 9.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia MedDRA version: 9.1 Level: LLT Classification code 10058110 Term: Dyslipidemia
Conditions
Interventions
Product Name: fenofibrate
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: fenofibrate 160
CAS Number: 49562-28-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
F. HOFFMANN-LA ROCHE LTD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and post-menopausal female, lipid treatment naïve or previously treated patients 2. Age 18 - 75 years (inclusive) 3. Low 130 mg/dL, but 150 mg/dL, but =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with secondary causes for Dyslipidemia (i.e. diabetes mellitus, hypothyroidism, obstructive liver disease, chronic renal failure) 2. Body Mass Index (BMI) = 30 kg/m2 3. Patients requiring drugs that increase LDL-C and decrease HDL-C [progestins, anabolic steroids, and corticosteroids] 4. Patients who drink alcohol excessively, defined as more than 21 units/week for males and more than 14 units/week for females. An alcohol unit is defined as 10 mL of absolute alcohol, 300 mL beer, 25 mL of a single spirit, or 100 mL of wine 5. History of or current alcohol or drug abuse 6. Use of an investigational drug in the 3 months prior to the screening visit 7. Any clinically significant medical condition that could interfere with the conduct of the study 8. Systolic blood pressure = 160 mmHg and/or diastolic blood pressure = 100 mmHg at the screening visit 9. History of obstructive biliary disorders, pancreatitis, collagen diseases, or auto-immune diseases 10. History of malignancy during the 3 years prior to the screening visit 11. Known or suspected diagnosis of hepatitis or human immunodeficiency virus (HIV) infection 12. Known thyroid dysfunction 13. Any past history of cerebro-vascular accident or coronary events, including unstable angina, myocardial infarction, angioplasty, or coronary artery bypass graft 14. Females who are pregnant or breast feeding and females of child bearing potential 15. Clinically significant hepatic, renal or cerebral disease 16. Hepatic transaminases or creatine phosphokinase > 2 times the upper limit of normal (ULN) at the screening visit 17. Unable or unwilling to comply with the protocol requirements, or deemed by the investigator to be unfit for the study 18. Subjects contraindicated for PPAR-a or slow release niacin treatment according to approved label 19. Lipid modifying drugs 20. Any concomitant therapy known to alter any of the parameters to assess (i.e., aspirin, except when aspirin is indicated for the prevention of severe flushes induced by Niaspan) 21. Hypersensitivity to PPARa or slow release niacin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of two lipid modifying drugs, fenofibrate (a PPAR-a agonist) and Niaspan (slow release niacin), on HDL-C plasma levels and HDL functionality in patients with low (< 40 mg/dL) and normal (between 40 and 59 mg/dL) HDL-C levels at baseline.;Secondary Objective: Secondary objectives: • To assess the relationship between HDL-C plasma levels and HDL functionality: - Reverse Cholesterol Transport (RCT) as measured by the capacity of serum to promote cell cholesterol efflux from macrophage and hepatoma cells. - HDL particle number, size and composition. • To correlate HDL particule number, size and composition with RCT. • To correlate plasma Apo-AI level with RCT. • To assess the relationship between HDL functionality and the whole lipid profile. Exploratory objectives: • To explore the effect of fenofibrate and slow release niacin on potential biomarkers of HDL functionality such as the: - Effect on Endothelial Function - Effect on HDL modifying enzymes/transporters - Anti-inflammatory effect - Anti-thrombotic effect - Change in oxidative stress;Primary end point(s): The percent and absolute changes from baseline in HDL-C plasma level will be the primary parameter to assess the direct effect of 6 weeks crossover treatment with two lipid modifying drugs, a PPARa agonist, fenofibrate, and slow release niacin, Niaspan. Due to the exploratory nature of the study no single primary parameter can be identified to assess the effect of 6 weeks crossover treatment with two lipid modifying drugs on HDL-C functionality. The following parameters describing HDL functionality and the reverse cholesterol transport (RCT) will be used as main study endpoints: • HDL particle number, size and composition • ApoA1 protein level • Capacity of serum to promote cell cholesterol efflux from macrophages and hepatoma cells | — |
Countries
France, Italy
Outcome results
None listed