Usage of a new pharmacological agent of ultra-small phospholipid nanoparticles (micelles) in the treatment of combined hyperlipidemia

Abstract

Abstract Background and aims Based on the developed technology of prerparation of ultra small size phospholipid nanoparticles without the use of detergents/surfactants and stabilizers drug preparation, exhibiting hypolipidemic properties has been obtained. Preclinical studies have shown that phospholipid nanoparticles of 20–30 nm (PLN) activate reverse cholesterol transport. PLN is now at the stage of clinical trials (Phase II study completed). The aim of the study was to compare the efficacy, safety and tolerability of PLN relative to placebo in the treatment of combined hyperlipidemia. Methods This Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted at 4 centers. The patients (pts) received PLN or placebo (1:1), powder for oral solution preparation (in an aqueous environment is a nanoemulsion with a particle size of 20–30 nm), 500 mg (sachet) orally 2 times a day for 12 weeks. Lipid parameters, safety and tolerability were measured. The data is presented in M (s), Me (lq; hq). Mann-Whitney U Test was to compare the significant difference of groups. P value <0.05 was considered statistically significant. Results A total of 100 pts with combined hyperlipidemia were randomized (age 35–70 years, males 58%).The mean age of patients was 56.4 (10.2) years. Mean total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), TG, and apolipoprotein B 100 (apoB) levels at baseline were 5.59 (0.8) mmol/l, 4.51 (0.75) mmol/l, 2.38 (0.6) mmol/l and 114.26 (24.96) mg/dl, respectively (n=100). Mean high-density lipoprotein cholesterol (HDL-C) and Lp(a) levels at baseline were 1.0 (0.25) mmol/l and 21.1 (3.9; 20.3)mg/dl, respectively (n=100). At Week 12, PLT significantly reduced total cholesterol, non-HDL-C levels, TG and apo B compared to placebo (p=0.02, p=0.03, p=0.001 and p=0.02, respectively). At the same time, the mean HDL-C level was significantly increased (p=0.03). The drug was well tolerated and no clinically significant laboratory abnormalities were detected. Conclusions This study demonstrates that therapy with PLT is well tolerated in additional beneficial effects on key lipid parameters in patients with moderate combined hyperlipidemia. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Ministry of industry and trade