MEDI6012: Recombinant Human Lecithin Cholesterol Acyltransferase, High-Density Lipoprotein, and Low-Density Lipoprotein Receptor-Mediated Reverse Cholesterol Transport.

Journal of the American Heart Association
Richard T GeorgeBoaz Hirshberg

Abstract

Background MEDI6012 is recombinant human lecithin cholesterol acyltransferase, the rate-limiting enzyme in reverse cholesterol transport. Infusions of lecithin cholesterol acyltransferase have the potential to enhance reverse cholesterol transport and benefit patients with coronary heart disease. The purpose of this study was to test the safety, pharmacokinetic, and pharmacodynamic profile of MEDI6012. Methods and Results This phase 2a double-blind study randomized 48 subjects with stable coronary heart disease on a statin to a single dose of MEDI6012 or placebo (6:2) (NCT02601560) with ascending doses administered intravenously (24, 80, 240, and 800 mg) and subcutaneously (80 and 600 mg). MEDI6012 demonstrated rates of treatment-emergent adverse events that were similar to those of placebo. Dose-dependent increases in high-density lipoprotein cholesterol were observed with area under the concentration-time curves from 0 to 96 hours of 728, 1640, 3035, and 5318 should be: mg·h/mL in the intravenous dose groups and 422 and 2845 mg·h/mL in the subcutaneous dose groups. Peak mean high-density lipoprotein cholesterol percent change was 31.4%, 71.4%, 125%, and 177.8% in the intravenous dose groups and 18.3% and 111.2% in the subcuta...Continue Reading

References

Nov 1, 1988·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·P W WilsonW P Castelli
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·J M HoegH B Brewer
May 18, 2004·Journal of Lipid Research·Charles C SchwartzPatricia S Cooper
Jul 11, 2007·Current Opinion in Lipidology·Benjamin J AnsellAlan M Fogelman
Nov 7, 2007·The New England Journal of Medicine·Philip J BarterUNKNOWN ILLUMINATE Investigators
Oct 29, 2008·Journal of Lipid Research·Mohamad NavabAlan M Fogelman
Nov 12, 2009·JAMA : the Journal of the American Medical Association·UNKNOWN Emerging Risk Factors CollaborationJohn Danesh
Nov 17, 2011·The New England Journal of Medicine·William E BodenWilliam Weintraub
Apr 18, 2012·Circulation·Robert S RosensonLaurent Yvan-Charvet
Nov 7, 2012·The New England Journal of Medicine·Gregory G SchwartzUNKNOWN dal-OUTCOMES Investigators
May 2, 2014·European Heart Journal·Jean-Claude TardifUNKNOWN Can HDL Infusions Significantly QUicken Atherosclerosis REgression (CHI-SQUARE) Investigators
Nov 19, 2014·The New England Journal of Medicine·Anand RohatgiPhilip W Shaul
Nov 14, 2015·Journal of the American College of Cardiology·Stephen J NichollsDaniel J Rader
Apr 9, 2016·Journal of Clinical Lipidology·Robert D ShamburekAlan T Remaley
Jul 16, 2016·Circulation. Cardiovascular Genetics·Jean-Claude TardifMarie-Pierre Dubé
May 18, 2017·The New England Journal of Medicine·A Michael LincoffUNKNOWN ACCELERATE Investigators
Aug 30, 2017·The New England Journal of Medicine·UNKNOWN HPS3/TIMI55–REVEAL Collaborative GroupMartin J Landray
Oct 13, 2017·Science Translational Medicine·Sarah E HeywoodBronwyn A Kingwell
Jan 26, 2021·European Heart Journal. Cardiovascular Pharmacotherapy·Marc P BonacaMarc S Sabatine

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.