Evaluation of Safety and Efficacy of AVE5530 as add-on to Ongoing High Doses of Statins in Patients With Primary Severe Hypercholesterolemia

Study Overview
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Brief Summary
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The present study is assessing the efficacy and safety of AVE5530 (25 mg and 50 mg) in add-on to ongoing treatment with high doses of statin in a double-blind manner in comparison with placebo, in the management of patients with severe primary hypercholesterolemia considered as inadequately controlled despite their ongoing statin treatment. The main objective is to evaluate the effects of the association AVE5530+statin on LDL-C level reduction after 12 weeks of treatment. The effects of AVE5530 on other lipid parameters will be assessed as secondary objectives.

Detailed Description
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The two doses of AVE5530 tested in this study are 25 mg and 50 mg taken in the evening, with dinner dosing. The study will include a pre-randomization phase up to 6 weeks, a double-blind treatment period of at least 12 months and can be variably extended up to approximately 18 months.

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of AVE5530 When Added to Ongoing Stable Statin Therapy at High Doses in Patients With Severe Primary Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: AVE5530
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with severe primary hypercholesterolemia and cholesterol levels not controlled on ongoing stable statin treatment at maximum doses. Exclusion Criteria: LDL-C levels > 250 mg/dL (6.48 mmol/L) or < 100 mg/dL (2.59 mmol/L) Triglycerides >350 mg/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 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 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg/day AVE5530<br> | Drug: AVE5530<br>* one tablet in the evening with dinner in addition to high doses of statin treatment<br>|
| Experimental: 50 mg/day AVE5530<br> | Drug: AVE5530<br>* one tablet in the evening with dinner in addition to high doses of statin treatment<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* one tablet in the evening with dinner in addition to high doses of statin treatment<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 and Apo-B |  | At 12 weeks, 6 months and 12 months |