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

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

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

Study Overview

• Status: Terminated
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: placebo; Drug: AVE5530; Drug: atorvastatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1736
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Puerto Rico, Puerto Rico
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

15

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: Davidson Michael, MD, Radiant Research - 515 North State Street Suite 2700 Chicago Illinois (US)

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: August 25, 2008
• First Submitted That Met QC Criteria: August 25, 2008
• First Posted (Estimate): August 26, 2008

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: April 15, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: primary hypercholesterolemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: EFC6911