Study of the Tolerability, Safety, Pharmacokinetics and Pharmacodynamics of SAR236553 (REGN727)

• Pain using present pain intensity (PPI) verbal questionnaire [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
• Erythema at injection site by measuring diameter and qualitative assessment [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
• Edema at injection site by measuring diameter and qualitative assessment [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

• Assessment of PK parameter - time to maximum concentration (tmax) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
• Assessment of PK parameter - maximum concentration (Cmax) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
• Assessment of PK parameter - area under curve (AUC) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
• Assessment of PK parameter - cluster of differentation (CD) biomarker (CD29) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
• Assessment of PK parameter - terminal elimination half-life (t1/2z) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
• Pharmacodynamics: Change in LDL-C from baseline [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
• Number of participants with Adverse Events [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]

Primary Objective:

Injection Site Tolerability

Secondary Objective:

• To assess the safety profile of SAR236553/REGN727
• To assess the pharmacokinetic-pharmacodynamic relationship pf SAR236553/REGN727

The total duration of study for each subject is up to 15 weeks including a screening period up to 3 weeks.

• Experimental: SAR236553/REGN727 - Dose A
  A single subcutaneous injection of Dose A
  Intervention: Drug: SAR236553/REGN727
• Experimental: SAR236553/REGN727 - Dose B
  A single subcutaneous injection of Dose B
  Intervention: Drug: SAR236553/REGN727

Inclusion Criteria:

• Serum LDL-C levels>100 mg/dL at screening visit.
• Male or female subject, between 18 and 65 years inclusive.
• Body weight between 50.0 and 95.0 kg inclusive if male, between 40.0 kg and 85.0 kg inclusive if female, body mass index (BMI) between 18.0 and 30.0 kg/m² inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
• Normal vital signs after 10 minutes resting in supine position.
• Normal standard 12-lead ECG after 10 minutes resting in supine position.
• Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects.
• If female, subject must use a double contraception method, except if she is sterilized for more than 3 months or postmenopausal.

Exclusion Criteria:

• Subjects indicated for the use of statins according to criteria in National Cholesterol Education Program adult treatment panel III Guidelines, as updated in 2004 (see Appendix C).
• Initiation of a new diet or major change to a previous diet within 4 weeks prior to Screening (Day -21 to -2). Subjects must be willing to maintain a consistent diet for the duration of the study.
• Use of a medication or nutraceutical in order to alter serum lipids within 4 weeks prior to screening (Day -21 to -2), including but not limited to statins, ezetimibe, fibrates, niacin, or omega-3 fatty acids, bile acid resins.
• Fasting serum triglycerides >200 mg/dL measured after an 8 to 12 hour fast.
• History of a hypersensitivity reaction to doxycycline or similar compound.

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