P1106
Direct augmentation of cholesterol efflux capacity in AMI patients: a PKPD substudy of AEGIS-I

Extract

Background: CSL112 is human apolipoprotein A-I (apoA-I), the main functional component of HDL-C. It is in development to reduce the risk of cardiovascular death, myocardial infarction and stroke (ie, MACE) after acute myocardial infarction (AMI). HDL function as assessed by cholesterol efflux capacity (CEC) has been correlated with a lower risk for MACE in stable CAD patients.

Purpose: To describe the PK (apoA-I) and PD (CEC) profile of CSL112 after 1st infusion in subjects who had an AMI and participated in the AEGIS-I PKPD substudy.

Methods: AEGIS-I was a randomized, double-blind, placebo controlled, dose-ranging phase 2b trial assessing the safety and tolerability of 4 weekly 2h infusions of CSL112 in AMI subjects with normal renal function (NRF) and mild renal impairment (MRI). The PKPD substudy was conducted in 63 subjects stratified by renal function and randomly assigned 3:3:2 within the substudy to 2g (n=24) or 6g (n=21) CSL112 or placebo (n=18). Venous blood samples were collected at multiple timepoints for PKPD assessments up to 168h after CSL112 administration. PKPD parameters of the 1st infusion were generated using a noncompartmental analysis.