Evaluation of Efficacy and Safety of AVE5530 Co-administered With Atorvastatin in Primary Hypercholesterolemia

Study Overview
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Brief Summary
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The present study is assessing the efficacy and safety of AVE5530 (25mg and 50mg) co-administered with all approved doses of atorvastatin in a double-blind comparison with placebo, AVE5530 alone and atorvastatin alone in the management of patients with primary hypercholesterolemia. The main objective is to evaluate the effects of the association AVE5530+atorvastatin on LDL-C level reduction after 12 weeks of treatment. The effects of AVE5530+atorvastatin on other lipid parameters will be assessed as secondary objectives

Detailed Description
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The study will include a 2 week pre-randomization placebo lead-in phase. There will be a 12- week double-blind treatment period for both components AVE5530 and atorvastatin, followed by a 40-week period with maintenance of double-blind design for AVE5530 component and open label for atorvastatin component transitioning at 20 mg for all patients with subsequent titration, if necessary, based on regular LDL-cholesterol monitoring. The treatment period can be variably extended up to approximately 18 months with double-blind for AVE5530 component and open-label for atorvastatin.

Official Title
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A Multicenter, Randomized, Placebo-controlled, Factorial Design, 12-month Study to Evaluate the Efficacy and Safety of AVE5530 25 mg/Day and 50 mg/Day Co-administered With All Registered Atorvastatin Strengths Ranging From 10 mg to 80 mg in Patients With Primary Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: AVE5530
* Drug: atorvastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with high cholesterol levels either not receiving or willing and able to discontinue ongoing lipid-lowering therapy Exclusion Criteria: LDL-C levels > 250 mg/dL (6.48 mmol/L) Triglycerides levels > 350mg/dL (3.95 mmol/L) Conditions / situations such as: presence of any clinically significant uncontrolled endocrine disease known to influence lipids levels Active liver disease High estimated risk of Coronary Heart Disease Recent history of congestive heart failure , of unstable angina pectoris, myocardial infarction, coronary bypass surgery or angioplasty, or Unstable or severe peripheral artery disease Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody or Known to be Human Immunodeficient Virus (HIV) positive Pregnant or breast-feeding women, Women of childbearing potential not protected by effective contraceptive method of birth control (including oral contraceptives) and/or who are unwilling or unable to be tested for pregnancy prior to exposure to the Investigational Product Hypersensitivity to any component of atorvastatin Concurrent administration of Cytochrome P450 3A4 inhibitors (e.g. cyclosporine, erythromycin, clarithromycin, and azole antifungals) should be avoided as increasing the risk of myopathy with atorvastatin The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: placebo<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 2<br>AVE5530 25mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 3<br>AVE5530 50mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>|
| Active Comparator: 4<br>atorvastatin 10mg | Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 5<br>atorvastatin 10mg + AVE5530 25mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 6<br>atorvastatin 10mg + AVE5530 50mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Active Comparator: 7<br>atorvastatin 20mg | Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 8<br>atorvastatin 20mg + AVE5530 25mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 9<br>atorvastatin 20mg + AVE5530 50mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Active Comparator: 10<br>atorvastatin 40mg | Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 11<br>atorvastatin 40mg + AVE5530 25mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 12<br>atorvastatin 40mg + AVE5530 50mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Active Comparator: 13<br>atorvastatin 80mg | Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 14<br>atorvastatin 80mg + AVE5530 25mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|
| Experimental: 15<br>atorvastatin 80mg + AVE5530 50mg | Drug: AVE5530<br>* oral administration once daily in the evening with dinner<br>Drug: atorvastatin<br>* oral administration once daily in the evening with dinner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in calculated LDL-C |  | At week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in calculated LDL-C |  | At 6 months and 12 months | 
| Percent change from baseline in total cholesterol, HDL-C, TG, Apo-A1, Apo-B and CRP |  | At week 12, 6 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary hypercholesterolemia