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

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

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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 643
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia
      • sanofi-aventis Australia & New Zealand administrative office
• Belgium
  • Diegem, Belgium
    • Sanofi-Aventis Administrative Office
• Bulgaria
  • Sofia, Bulgaria
    • Sanofi-Aventis Administrative Office
• Canada
  • Laval, Canada
    • Sanofi-Aventis Administrative Office
• Czech Republic
  • Praha, Czech Republic
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Israel
  • Natanya, Israel
    • Sanofi-Aventis Administrative Office
• Netherlands
  • Gouda, Netherlands
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Slovakia
  • Brastislava, Slovakia
    • Sanofi-Aventis Administrative Office
• South Africa
  • Midrand, South Africa
    • Sanofi-Aventis Administrative Office
• Ukraine
  • Kiev, Ukraine
    • 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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; one tablet in the evening with dinner; in addition to high doses of statin treatment
Experimental: 25 mg/day AVE5530	Drug: AVE5530; one tablet in the evening with dinner; in addition to high doses of statin treatment
Experimental: 50 mg/day AVE5530	Drug: AVE5530; one tablet in the evening with dinner; in addition to high doses of statin treatment

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 and Apo-B	At 12 weeks, 6 months and 12 months

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: October 3, 2008
• First Submitted That Met QC Criteria: October 3, 2008
• First Posted (Estimate): October 6, 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

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: EFC10841; EudraCT 2008-002849-23