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- W1511320686 abstract "Introduction: MDCO-216, a complex of dimeric recombinant apolipoprotein A-I Milano (apoA-I M) and a phospholipid (POPC), is currently under development to improve cardiovascular outcomes by reducing plaque burden in patients with atherosclerotic disease. An earlier version of MDCO-216 has been shown effective in animal models and in patients with ACS. The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD) and safety of MDCO-216, manufactured by an improved process, first time in stable coronary artery disease (CAD) patients. Methods: 24 patients with known stable CAD received a single dose of MDCO-216 (10, 20, 30 or 40 mg/kg) or placebo (in 2:1 ratio) as a 2 hour IV infusion in a double-blind, randomised design. Blood samples were collected for PK and anti-drug Antibody (ADA) analysis. Ex-vivo cholesterol efflux assays were used as exploratory PD biomarkers for MDCO-216 activity. Results: Plasma mean T 1/2 of MDCO-216 ranged from 45 to 59 hours (53 hr. in average) and median T max ranged between 2 to 3 hours. No obvious difference in CL was observed with increases in dose and this ranged from 0.7 to 0.8 mL/hr/kg. Exposure parameters (C max and AUC) increased with dose in a dose-proportional manner. No ADA was detected with any dose at any time point. Dose-dependent increases in ABCA1-mediated efflux (up to 4-fold above baseline) and smaller increases of SRB1-mediated efflux occurred rapidly after infusion. The dose-response analysis for ABCA1-mediated efflux best fitted into a sigmoid E max (maximum effect) PD model and predicts an E max of 12.7% which saturates around a 16 mg/kg dose (see figure). Conclusions: This data is consistent with the findings of the previous IVUS study in ACS patients with MDCO-216 where maximum regression of atherosclerotic plaque burden was seen at a dose of 15 mg/kg; and support further development of this agent as a potential treatment for atherosclerotic disease." @default.
- W1511320686 created "2016-06-24" @default.
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- W1511320686 date "2014-11-25" @default.
- W1511320686 modified "2023-09-23" @default.
- W1511320686 title "Abstract 13357: MDCO-216 (ApoA-I Milano/POPC) Induces Reverse Cholesterol Transport in Stable Coronary Artery Disease Patients with a Dose Proportional Pharmacokinetics after Single Ascending Doses" @default.
- W1511320686 doi "https://doi.org/10.1161/circ.130.suppl_2.13357" @default.
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