A 12-week Study to Compare the Efficacy and Safety of Fixed Combinations of Fenofibrate/Simvastatin 145/20mg and Fenofibrate/Simvastatin 145/40mg Tablets Versus Fenofibrate or Simvastatin Monotherapies in Subjects With Abnormal Blood Levels of Fats (Lipids) and at High Risk of Cardiovascular Disease

Study Overview
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Brief Summary
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This is a double-blind, randomized study designed to compare the efficacy and safety of two fixed combinations of fenofibrate / simvastatin 145/20 mg and fenofibrate / simvastatin 145/40 mg tablets vs. matching monotherapies in subjects with abnormal fat (lipids) in the blood and at high risk of cardiovascular disease. Fenofibrate is a treatment that lowers fat in blood. It is prescribed in patients with high levels of triglycerides (TG). The drug has been marketed in more than 80 countries since 1975. Simvastatin is also used for the treatment of patients with a high level of cholesterol. These have also been marketed worldwide for more than 20 years. It is important to treat high levels of fats in the blood because it has been shown that even mildly elevated level of lipids in the blood can lead to diseases of the blood vessels. It has been shown in several studies and in clinical practice that the combination of fenofibrate plus simvastatin can lead to improved effects on blood fats, compared to treatment with simvastatin or fenofibrate alone. The main objective of the study is to compare the efficacy of the two fixed-combinations (FC) -fenofibrate/simvastatin 145/20 mg tablet and fenofibrate/simvastatin 145/40 mg tablet in reducing TG and increasing high density lipoprotein cholesterol (HDL-C) versus simvastatin 20 mg or 40 mg, and in reducing low density lipoprotein cholesterol (LDL-C) versus fenofibrate 145 mg.

Official Title
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A 12-week, Double-blind, Randomized Study to Compare the Efficacy and Safety of Fixed Combinations of Fenofibrate / Simvastatin 145/20mg and Fenofibrate / Simvastatin 145/40mg Tablets vs. Matching Monotherapies in Dyslipidemic Subjects at High Risk of Cardiovascular Disease.

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: Fixed Combination of Fenofibrate/simvastatin 145/20 mg
* Drug: Simvastatin 20 mg
* Drug: Fenofibrate 145 mg
* Drug: Fixed Combination of Fenofibrate/simvastatin 145/40 mg
* Drug: Simvastatin 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either gender (tentatively 50 percent females to be included and if of childbearing potential she must agree to use medically acceptable methods of contraception from the time of signing the informed consent until 7 days following administration of the last treatment or dose of study medication). Accepted contraceptive methods are implants, injectables, combined oral contraceptives, intra-uterine device or sexual abstinence. between 18 (inclusive) and 80 years With mixed dyslipidemia with fasting lipid results of a blood sample taken at inclusion and after at least 3 months of any statin monotherapy (excluding simvastatin 80 mg, atorvastatin 40 mg and 80 mg, rosuvastatin 20 mg and 40 mg): TG higher than/equal to 1.71 mmol/L (higher than/equal to 150 mg/dL) and LDL-C higher or equal to 1.81 mmol/L (higher or equal 70 mg/dL) but smaller than/equal to 3.36 mmol/L (smaller than/equal to 130 mg/dL) High risk or very high risk based on known CardioVascular Disease (CVD) or type 2 diabetes or type 1 diabetes with microalbuminuria or a Systematic Coronary Risk Estimation (SCORE) chart risk ≥ 5percent Aspartate aminotransferase and/or alanine aminotransferase smaller than/equal to 2 times the Upper Normal of Limit (UNL) Exclusion Criteria: 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 or arachis oil or soy lecithin, or related products, Pregnant or lactating women, Unable or unwilling to comply with the protocol and the recommended diet, Likely to withdraw from the study before its completion, Having received an investigational drug or vaccine in the last 30 days before date of inclusion, or still participating in such a trial at Visit 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenofibrate/simvastatin 145/20 mg<br> | Drug: Fixed Combination of Fenofibrate/simvastatin 145/20 mg<br>* Fenofibrate/simvastatin oval biconvex film-coated tablet, 145 mg / 20 mg, once daily, 12 weeks<br>|
| Active Comparator: Simvastatin 20 mg<br> | Drug: Simvastatin 20 mg<br>* Simvastatin generic tablet over-encapsulated, 20 mg, once daily, 12 weeks<br>|
| Active Comparator: Fenofibrate 145 mg<br> | Drug: Fenofibrate 145 mg<br>* Fenofibrate, tablet, 145 mg, once daily, 12 weeks<br>|
| Experimental: Fenofibrate/simvastatin 145/40 mg<br> | Drug: Fixed Combination of Fenofibrate/simvastatin 145/40 mg<br>* Fenofibrate/simvastatin film-coated tablet 145 mg / 40 mg, once daily, 12 weeks<br>|
| Active Comparator: Simvastatin 40 mg<br> | Drug: Simvastatin 40 mg<br>* simvastatin, generic tablet over-encapsulated, 40 mg, once daily, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Change of TG (Triglyceride) | Collection and measurement of blood samples. | from baseline to 12 weeks of treatment | 
| Percentage of Change of HDL-C (High Density Lipoprotein Cholesterol) | Collection and measurement of blood samples. | from baseline to 12 weeks of treatment | 
| Percentage of Change of LDL-C (Low Density Lipoprotein Cholesterol) | Collection and measurement of blood samples. | from baseline to 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Non-HDL (High Density Lipoprotein)-C From Baseline | Collection and measurement of blood samples | 12 weeks | 
| Percentage of TC (Triglyceride) From Baseline | Collection and measurement of blood samples | 12 weeks | 
| Percentage of Apolipoprotein AI From Baseline | Collection and measurement of blood samples | 12 weeks | 
| Percentage of Apolipoprotein B From Baseline | Collection and measurement of blood samples | 12 weeks | 
| Percentage of High-sensitivity C-reactive Protein (hsCRP) From Baseline | Collection and measurement of blood samples | 12 weeks | 
| Percentage of Subjects Meeting Target Levels of Lipids (According to Very High or High Risk) | Collection and measurement of blood samples | 12 weeks | 
| Adverse Events | Collection and measurement of blood samples | 12 weeks | 
| Creatine Kinase (CK) | Collection and measurement of blood samples | 12 weeks | 
| Alanine Aminotransferase (ALT) | Collection and measurement of blood samples | 12 weeks | 
| Plasma Creatinine | Collection and measurement of blood samples | 12 weeks | 
| Total Bilirubin | Collection and measurement of blood samples | 12 weeks | 
| Cystatin C | Collection and measurement of blood samples | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibrates, Dyslipidemia