Injection Site Tolerability, Safety, Pharmacokinetics and Pharmacodynamics Study After a Single Dose Subcutaneous Treatment of Alirocumab SAR236553 (REGN727)

Study Overview
=================
Brief Summary
-----------------
Primary Objective: Injection Site Tolerability Secondary Objectives: To assess the safety profile of alirocumab SAR236553 (REGN727) To assess the pharmacokinetic-pharmacodynamic relationship of alirocumab SAR236553 (REGN727)

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

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: alirocumab SAR236553 (REGN727)
* Drug: alirocumab SAR236553 (REGN727)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Serum troponin I level should not exceed the upper laboratory limit of normal. 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. Serum LDL-C levels>100 mg/dL at screening visit. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alirocumab SAR236553 (REGN727) - Dose A<br>A single subcutaneous injection of Dose A | Drug: alirocumab SAR236553 (REGN727)<br>* Pharmaceutical form:Solution Route of administration: Subcutaneous<br>|
| Experimental: alirocumab SAR236553 (REGN727) - Dose B<br>A single subcutaneous injection of Dose B | Drug: alirocumab SAR236553 (REGN727)<br>* Pharmaceutical form:Solution Route of administration: Subcutaneous<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain using present pain intensity (PPI) verbal questionnaire |  | 6 weeks | 
| Erythema at injection site by measuring diameter and qualitative assessment |  | 6 weeks | 
| Edema at injection site by measuring diameter and qualitative assessment |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter - time to maximum concentration (tmax) |  | Up to 12 weeks | 
| Assessment of PK parameter - maximum concentration (Cmax) |  | Up to 12 weeks | 
| Assessment of PK parameter - area under curve (AUC) |  | Up to 12 weeks | 
| Assessment of PK parameter - cluster of differentiation (CD) biomarker (CD29) |  | Up to 12 weeks | 
| Assessment of PK parameter - terminal elimination half-life (t1/2z) |  | Up to 12 weeks | 
| Pharmacodynamics: Change in LDL-C from baseline |  | Up to 12 weeks | 
| Number of participants with Adverse Events |  | Up to 12 weeks |