Effect of Alirocumab on Lipid Metabolism in Adults With Elevated LDL-Cholesterol

Study Overview
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Brief Summary
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Primary Objective: To assess the effects of subcutaneous (SC) doses of alirocumab on the elimination (measured by Fractional Clearance Rate (FCR)) of apolipoprotein B (apoB) in low density lipoprotein (LDL) in adults with mildly elevated LDL-cholesterol (LDL-C). Secondary Objectives: To assess the effects of SC doses of alirocumab on: Various parameters of the metabolism and turnover in plasma of different lipoproteins Plasma lipids concentration: total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, low density lipoprotein cholesterol (LDL-C), apoB, lipoprotein(a) (Lp(a)) Lipoprotein particle size profile PCSK9 (free and total) concentrations in serum To assess safety and tolerability of alirocumab. To assess emergence of anti-alirocumab antibodies. To document serum alirocumab concentrations.

Detailed Description
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Total duration of the study per subject is 26 weeks, including a screening period of ≤ 4 weeks, placebo treatment period of 4 weeks, alirocumab treatment period of 10 weeks, and a follow up period of 8 weeks.

Official Title
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A Phase 1 Study of the Effects of Subcutaneous Doses of Alirocumab on Lipid and Lipoprotein Metabolism in Adults With Mildly Elevated LDL-Cholesterol

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: alirocumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Generally healthy; LDL-C level in serum or plasma ≥ 100 mg/dL and < 190 mg/dL at Screening. Exclusion criteria: LDL-C ≥ 160 mg/dL at Screening if more than 2 major Coronary Heart Disease risk factors, as defined in National Cholesterol Education Program guidelines. Receiving treatment of any kind for hyperlipidemia within 6 weeks of enrollment. 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: Basic Science
Intervention Model: Crossover Assignment
Interventional Model Description: Single-sequence crossover
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo - Alirocumab<br>Injection through subcutaneous (SC) administration, placebo for 4 weeks then, alirocumab for 10 weeks | Drug: alirocumab<br>* Pharmaceutical form:Solution for injection Route of administration: Subcutaneous<br>* Other names: Praluent;Drug: Placebo<br>* Pharmaceutical form:Solution for injection Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in Fractional Clearance Rate of apolipoprotein B (apoB) in Low Density Lipoproteins (pools/day) in plasma during alirocumab treatment |  | baseline and at 12 days after last dose of alirocumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipids turnover parameters measured in isolated Very Low Density Lipoproteins (VLDL), Intermediate Density Lipoproteins (IDL), Low Density Lipoproteins (LDL) and High Density Lipoproteins (HDL) |  | baseline and at 12 days after last dose of alirocumab | 
| Change in post-heparin hepatic lipase and lipoprotein lipase activities |  | baseline and at 2 days after last dose of alirocumab | 
| Change in lipids and apolipoproteins in plasma lipids panel |  | baseline and at 2 days and at 11 days after last dose of alirocumab | 
| Assessment of Lipoprotein particle size profiles |  | baseline and at 2 days and at 11 days after last dose of alirocumab | 
| Assessment of serum concentrations of PCSK9 |  | baseline and up to 2 weeks after last dose of alirocumab | 
| Assessment of safety parameters (clinical laboratory, ECG, vital signs) |  | up to 10 weeks after last dose of alirocumab | 
| Assessment of the serum concentration of alirocumab |  | baseline and up to 2 weeks after last dose of alirocumab | 
| Assessment of the serum concentration of anti-alirocumab antibodies |  | baseline and up to 10 weeks after last dose of alirocumab |