Assessment of lipoprotein profiles study (ALPS) and antioxidant activity in healthy subjects treated with AGI-1067

• Published in: Journal of clinical lipidology 2007-08, Vol.1 (4), p.271-279
• Main Authors: Davidson, Michael H., MD, Smith, Joseph, MD, Scott, Robert, MD, Small, Robert, PhD, Choi, Jasmine, MS, Ishida, Brian Y., PhD, Kane, John P., MD, PhD
• Format: Article
• Language: English
• Subjects: AGI-1067; Antiatherosclerotic; Antioxidant activity; Cardiovascular; High-density lipoprotein; Vascular oxidative-inflammatory cascade inhibitor
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2007.07.005

Abstract Background AGI-1067 (succinobucol) is a phenolic derivative of probucol that inhibits the vascular oxidative-inflammatory cascade and is intended to have an improved clinical profile. Objective The Assessment of Lipoprotein Profiles (ALPS) study evaluated the effects of AGI-1067 on lipid, antioxidant, antiinflammatory and safety profiles in healthy subjects. Methods This was a double-blind, placebo-controlled, 12-week, multicenter trial. Eligible subjects, aged 18 to 65 years, had low-density lipoprotein cholesterol (LDL-C) ≤ 190 mg/dL, triglyceride (TG) ≤ 600 mg/dL and Framingham risk 130 mg/dL showed the largest decreases in HDL-C and ApoA-I, while subjects with LDL-C ≤130 mg/dL had insignificant changes in both parameters. Changes in cholesteryl ester transfer protein mass were significantly correlated ( P < 0.0001) with LDL-C changes, but not HDL-C. Paraoxonase activity increased with AGI-1067 vs little change in placebo (+1.78 vs +0.15 U/L, respectively; P = 0.077). HDL particles isolated from AGI-1067 treated subjects showed significant antioxidant potency vs HDL particles from placebo subjects (thiobarbituric acid reactive substances in a LDL oxidation assay decreased −25.88% vs +7.88, respectively; P = 0.011). Conclusion The ALPS study demonstrated that AGI-1067 had minor effects on LDL and HDL cholesterol. More dramatic effects were observed for HDL-associated paraoxonase and thiobarbituric acid reactive substances activity, suggesting that the antiatherosclerotic properties of AGI-1067 may involve an HDL antioxidant mechanism consistent with inhibition of the oxidative-inflammatory cascade, rather than involving a lipid regulating pathway.