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
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Sanofi
- Enrollment
- 1,736
- Locations
- 1
- Primary Endpoint
- Percent change from baseline in calculated LDL-C
Study Overview
Brief Summary
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
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
1
Intervention: placebo (Drug)
2
AVE5530 25mg
Intervention: AVE5530 (Drug)
3
AVE5530 50mg
Intervention: AVE5530 (Drug)
4
atorvastatin 10mg
Intervention: atorvastatin (Drug)
5
atorvastatin 10mg + AVE5530 25mg
Intervention: AVE5530 (Drug)
8
atorvastatin 20mg + AVE5530 25mg
Intervention: AVE5530 (Drug)
5
atorvastatin 10mg + AVE5530 25mg
Intervention: atorvastatin (Drug)
6
atorvastatin 10mg + AVE5530 50mg
Intervention: AVE5530 (Drug)
6
atorvastatin 10mg + AVE5530 50mg
Intervention: atorvastatin (Drug)
7
atorvastatin 20mg
Intervention: atorvastatin (Drug)
8
atorvastatin 20mg + AVE5530 25mg
Intervention: atorvastatin (Drug)
9
atorvastatin 20mg + AVE5530 50mg
Intervention: AVE5530 (Drug)
9
atorvastatin 20mg + AVE5530 50mg
Intervention: atorvastatin (Drug)
10
atorvastatin 40mg
Intervention: atorvastatin (Drug)
11
atorvastatin 40mg + AVE5530 25mg
Intervention: AVE5530 (Drug)
11
atorvastatin 40mg + AVE5530 25mg
Intervention: atorvastatin (Drug)
12
atorvastatin 40mg + AVE5530 50mg
Intervention: AVE5530 (Drug)
12
atorvastatin 40mg + AVE5530 50mg
Intervention: atorvastatin (Drug)
13
atorvastatin 80mg
Intervention: atorvastatin (Drug)
14
atorvastatin 80mg + AVE5530 25mg
Intervention: AVE5530 (Drug)
14
atorvastatin 80mg + AVE5530 25mg
Intervention: atorvastatin (Drug)
15
atorvastatin 80mg + AVE5530 50mg
Intervention: AVE5530 (Drug)
15
atorvastatin 80mg + AVE5530 50mg
Intervention: atorvastatin (Drug)
Outcomes
Primary Outcomes
Percent change from baseline in calculated LDL-C
Time Frame: At week 12
Secondary Outcomes
- 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)