Mechanisms
ALPS study finds CETP mass changes track LDL cholesterol, not HDL, with the probucol derivative AGI-1067 (J Clin Lipidol 2007)
Original title: Assessment of lipoprotein profiles study (ALPS) and antioxidant activity in healthy subjects treated with AGI-1067
In this double-blind, placebo-controlled, 12-week trial, 127 healthy subjects received AGI-1067 (succinobucol), a phenolic probucol derivative that inhibits the vascular oxidative-inflammatory cascade, or matching placebo. AGI-1067 produced only small changes in LDL cholesterol and apolipoprotein B versus placebo, but significantly lowered HDL cholesterol (minus 3.69 versus minus 0.29 mg/dL, P less than 0.001) and apolipoprotein A-I (P equals 0.021). Changes in CETP mass were significantly correlated with changes in LDL cholesterol (P less than 0.0001) but not with HDL cholesterol changes. HDL particles from AGI-1067-treated subjects also showed significantly greater antioxidant potency than placebo HDL, suggesting the antiatherosclerotic properties of AGI-1067 involve an HDL antioxidant mechanism rather than classical lipid regulation.
Original 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 <10%. Subjects were randomized 1:1 to oral 300 mg AGI-1067 (n = 127) or matching placebo (n = 127) once daily.
Results: AGI-1067 and placebo treatment had small changes (mean) in: LDL-C (+2.98 vs -1.52 mg/dL, respectively; P = 0.057), apolipoprotein B (+1.48 vs -1.91 mg/dL; P = 0.267), high-density lipoprotein cholesterol (HDL-C) [-3.69 vs -0.29 mg/dL; P < 0.001], and apolipoprotein (Apo) A-I (-10.43 vs -6.14 mg/dL; P = 0.021). Subjects with baseline LDL-C > 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.
infectionmechanismspharmacology
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.