Primary Hypercholesterolemia MedDRA version: 11.0 Level: LLT Classification code 10060375 Term:
Conditions
Interventions
Product Code: AVE5530
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: canosimibe
CAS Number: 768394-99-6
Current Sponsor code: AVE5530
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients can be included only if they satisfy the following criteria: • With severe primary hypercholesterolemia and confirmed insufficient control with ongoing atorvastatin or simvastatin or rosuvastatin treatment at the highest doses (80 mg, 80 mg or 40 mg respectively) for at least 6 weeks • With written informed consent obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria related to study methodology: • Age less than 18 years at Visit 1 • Administration of other investigational drugs within 30 days or 5 half lives prior to Visit 1 (whichever is the longest) • Patient who previously participated in another AVE5530 trial • Patient who will require, in addition to ongoing atorvastatin, simvastatin or rosuvastatin treatment at the highest doses (80 mg, 80 mg or 40 mg respectively), another lipid-lowering agent (other than the study medication) in the near future, based on investigator’s judgment • Patient in whom adjustment of the ongoing lipid lowering therapy as per protocol requirement would not be appropriate based on investigator’s judgment or who is not willing to undergo therapy adjustment • LDL-C levels 250 mg/dL (6.48 mmol/L) • Triglycerides > 350 mg/dL (3.95 mmol/L) • Known homozygous familial hypercholesterolemia • Conditions / situations such as: - Patients with conditions/concomitant diseases - Making them non-evaluable for the primary efficacy endpoint: such as presence of any clinically significant and not controlled endocrine disease known to influence serum lipids or lipoproteins. Patients on thyroid replacement therapy can be included if the dosage of thyroxine has been stable for at least 3 months prior to Visit 1 and their s- TSH (sensitive TSH) levels is within ±10% of the normal ranges of the Central Laboratory. - Any conditions considered to be medically sound by the investigator that would limit the patient’s safe participation in the study such as: - Active liver disease, as shown by but not limited to alanine aminotransferase (ALT) or aspartate amino-transferase (AST) = 3xUpper Limit Normal (ULN) range - Neutrophils < 1,500/mm3 - Platelets counts < 100 000/ mm3 - Unexplained CPK = 3xULN - Recent history (within 6 months of Visit 1 and through to randomization) of moderate or severe congestive heart failure [New York Heart Association (NYHA)Class III or IV] - Recent history of unstable angina pectoris, myocardial infarction, coronary bypass surgery or angioplasty within 6 months of study screening, - Unstable or severe peripheral artery disease within 6 months of Visit 1 and through to randomization - Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody - Known to be Human Immunodeficiency Virus (HIV) positive - Presence of any other conditions (e.g. geographic, social….) actual or anticipated that the investigator feels would restrict or limit the patient’s participation for the duration of the study - Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. - Administration of any lipid-lowering treatment other than the background statins allowed for the study (atorvastatin 80 mg, simvastatin 80 mg or rosuvastatin 40 mg) after visit 1. Exclusion criteria related to AVE5530 compound: • Pregnant or breast-feeding women, • Women of childbearing potential not protected by effective 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • The primary objective of this study is to assess the efficacy over 12 weeks (3 months) of AVE5530 25 mg and 50 mg as add-on therapy to ongoing stable high-dose statin on calculated LDL-C levels in comparison with placebo (ie statin alone) in patients with primary severe hypercholesterolemia. • Additional evaluations of LDL-C will be performed at week 12: - Percent change from baseline in LDL-C measured by ultracentrifugation - Proportion of patients achieving NCEP-ATPIII target goals for calculated LDL-C.;Secondary Objective: The secondary objectives of this study are as follows: • To assess the effects of AVE5530 25 mg/day and AVE5530 50 mg/day in comparison with placebo over 12 weeks in add-on therapy to ongoing stable high-dose statin on - Total-Cholesterol (Total-C) and - Apolipoprotein B (Apo-B) levels • To assess the safety and tolerability of AVE5530 25 mg/day and AVE5530 50 mg/day;Primary end point(s): Efficacy • The primary efficacy endpoint is the percent change from baseline to 12 weeks (3 months) in calculated Low Density Lipoprotein –Cholesterol (LDL-C) serum levels • Additional evaluations of LDL-C at week 12 are: - Percent change from baseline to 12 weeks in LDL-C measured by ultracentrifugation - Proportion of patients achieving NCEP-ATPIII target goals for calculated LDL-C at 12 weeks. | — |
Countries
Belgium, Czech Republic, France
Outcome results
None listed