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

Phase 1CompletedNCT01959971

Sanofi20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Hypercholesterolemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Percent change in Fractional Clearance Rate of apolipoprotein B (apoB) in Low Density Lipoproteins (pools/day) in plasma during alirocumab treatment

Time frame: baseline and at 12 days after last dose of alirocumab

Secondary Outcomes

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)

Time frame: baseline and at 12 days after last dose of alirocumab

Change in post-heparin hepatic lipase and lipoprotein lipase activities

Time frame: baseline and at 2 days after last dose of alirocumab

Change in lipids and apolipoproteins in plasma lipids panel

Time frame: baseline and at 2 days and at 11 days after last dose of alirocumab

Assessment of Lipoprotein particle size profiles

Time frame: baseline and at 2 days and at 11 days after last dose of alirocumab

Assessment of serum concentrations of PCSK9

Time frame: baseline and up to 2 weeks after last dose of alirocumab

Assessment of safety parameters (clinical laboratory, ECG, vital signs)

Time frame: up to 10 weeks after last dose of alirocumab

Assessment of the serum concentration of alirocumab