Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Combo II)

• Percent change in calculated LDL-C at Week 12 and 52 [ Time Frame: From baseline up to Week 52 ] [ Designated as safety issue: No ]
• Percent change in other lipid parameters at Week 12, Week 24 and 52 [ Time Frame: From baseline up to Week 52 ] [ Designated as safety issue: No ]
• Percent change in calculated LDL-C at Week 104 [ Time Frame: From baseline up to Week 104 ] [ Designated as safety issue: No ]
  From a mixed-effect model including all LDL-C values collected up to Week 104
• Percent change in other lipid parameters at Week 104 [ Time Frame: From baseline up to Week 104 ] [ Designated as safety issue: No ]

• Percent change in LDL-C [ Time Frame: From baseline up to week 12 ] [ Designated as safety issue: No ]
• Percent change in other lipid parameters [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).

Primary Objective of the study:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in patients with hypercholesterolemia at high cardiovascular (CV) risk.

Secondary Objectives:

• To evaluate the effect of alirocumab in comparison with ezetimibe on LDL-C at other time points.
• To evaluate the effect of alirocumab on other lipid parameters.
• To evaluate the safety and tolerability of alirocumab.

The maximum study duration will be 115 weeks per patient, including a 3 week screening period, 104 week randomized treatment period and 8 week follow-up period.

• Drug: Alirocumab

  Pharmaceutical form: Solution for injection

  Route of administration: Subcutaneous

  Other Names:

  • SAR236553
  • REGN727
• Drug: Placebo (for alirocumab)

  Pharmaceutical form: Solution for injection

  Route of administration: Subcutaneous

• Drug: Ezetimibe

  Pharmaceutical form: Encapsulated tablets

  Route of administration: Oral

• Drug: Placebo (for ezetimibe)

  Pharmaceutical form: Capsules

  Route of administration: Oral

• Experimental: Alirocumab
  Alirocumab injection through subcutaneous (SC) administration + placebo (for ezetimibe) orally.
  Interventions:

  • Drug: Alirocumab
  • Drug: Placebo (for ezetimibe)
• Active Comparator: Ezetimibe
  Placebo (for alirocumab) injection through subcutaneous (SC) administration + ezetimibe orally.
  Interventions:

  • Drug: Placebo (for alirocumab)
  • Drug: Ezetimibe

Inclusion criteria:

Patients with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin at stable dose for at least 4 weeks prior to the screening visit (Week -2).

Exclusion criteria:

• Age < 18 or legal age of adulthood, whichever is greater.
• Patients without established CHD or CHD risk equivalents.
• LDL-C <70 mg/dL (<1.81 mmol/L) and patients with a history of documented cardiovascular disease.
• LDL-C <100 mg/dL (<2.59 mmol/L) and patients without a history of documented CV disease.
• Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.