Hypercholesterolemia
Conditions
Brief summary
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
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.
Interventions
DRUGalirocumab
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Single-sequence crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Assessment of serum concentrations of PCSK9 | baseline and up to 2 weeks after last dose of alirocumab |
Countries
United States
Outcome results
None listed