Injection Site Tolerability, Safety, Pharmacokinetics, Pharmacodynamics in Different Single-Dose Treatments of Alirocumab SAR236553 (REGN727) in Healthy Subjects

Study Overview
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Brief Summary
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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
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Total duration for each subject (not including screening) will be approximately 85 days.

Official Title
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A Randomized Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics After Different Single-Dose Subcutaneous Treatments of SAR236553/REGN727 in Healthy Subjects

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: alirocumab SAR236553 (REGN727)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Serum LDL-C levels >100 mg/dL. Exclusion criteria: Subjects indicated for the use of statins according to criteria in Adult Treatment Program (ATP) III Guidelines, as updated in 2004. Initiation of a new diet or major change to a previous diet within 4 weeks prior to Screening. 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, including but not limited to statins, cholesterol absorption inhibitors, fibrates, niacin, bile acid resins, or red yeast rice. Fasting serum triglycerides >200 mg/dL measured after an 8-12 hour fast. 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
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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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) (Formulation A x 1)<br>A single subcutaneous injection of Formulation A | Drug: alirocumab SAR236553 (REGN727)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>|
| Experimental: alirocumab SAR236553 (REGN727) (Formulation B x 1)<br>A single subcutaneous injection of Formulation B | Drug: alirocumab SAR236553 (REGN727)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>|
| Experimental: alirocumab SAR236553 (REGN727) (Formulation A x 2)<br>2 single subcutaneous injections of Formulation A | Drug: alirocumab SAR236553 (REGN727)<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain using Present Pain Intensity (PPI) verbal questionnaire and Visual Analog Scale (VAS) |  | 15 days | 
| Erythema at injection site by measuring diameter and qualitative assessment |  | 15 days | 
| Edema at injection site by measuring diameter and qualitative assessment |  | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter - time to maximum concentration (tmax) |  | Up to 85 days | 
| Pharmacodynamics: Change in LDL-C from baseline |  | Up to 85 days | 
| Number of participants with Adverse Events |  | Up to 85 days | 
| Assessment of PK parameter - maximum concentration (Cmax) |  | Up to 85 days | 
| Assessment of PK parameter - area under curve (AUC) |  | Up to 85 days | 
| Assessment of PK parameter - area under curve versus time curve (AUC0-D29) |  | Zero to Day 29 | 
| Assessment of PK parameter - plasma concentration on Day 29 (C D29) |  | Day 29 | 
| Assessment of PK parameter - terminal elimination half-life (t1/2z) |  | Up to 85 days |