Abstract 11889: Phase Ib Study of Icosabutate, a Novel Structurally Enhanced Fatty Acid, in Subjects With Hypercholesterolemia
Introduction: Icosabutate, an orally active structurally enhanced fatty acid (SEFA), has demonstrated reductions in triglycerides (TG) and cholesterol in several rodent models of dyslipidemia and diabetes. In clinical single and multiple ascending dose studies, icosabutate was well tolerated and significantly lowered LDL-C, non-HDL-C, and TG in subjects with mixed dyslipidemia. This phase 1b study explored the lipid-lowering effects of icosabutate in subjects with hypercholesterolemia.
Methods: This was a randomized, double-blind, placebo-controlled study. Subjects with hypercholesterolemia treated with a statin for at least 3 months were screened. Statins were temporarily discontinued for at least 28 days prior to dosing and for the duration of the study. To qualify for the study, subjects were required to have an LDL-C ≥ 2.5 mmol/L (97 mg/dL) at the secondary screening visit and an increase in LDL-C of at least 20 % between the primary and secondary screening. Twenty four subjects were randomized to icosabutate 600 mg once daily or matching placebo in a 3:1 fashion and treated for 28 days. Safety and pharmacodynamics were evaluated. Results are reported as placebo-adjusted median percentage change from baseline (average of visit 2-4) to 24 hours after last dose (day 29).
Results: Six subjects received placebo and 18 subjects received icosabutate. Median baseline lipid values (mg/dL) placebo/ icosabutate: TC: 270 and 240; LDL-C: 174 and 166; and TG: 204 and 168. Compared to placebo, icosabutate reduced total cholesterol (17.4 %, p < 0.05), LDL-C (29.3 %, p<0.05), non-HDL-C (25.4 %, p<0.05), and apo B (22.8 %, p< 0.05). There was a non-significant increase in HDL-C. TG reductions were not statistically significant (12.6 %, ns), but both placebo and icosabutate subjects experienced large reductions from baseline (29 % versus 42 %).
Conclusions: In this randomized, double-blind, placebo-controlled phase Ib study in subjects with hypercholesterolemia, icosabutate demonstrated placebo-adjusted reductions in total cholesterol, LDL-C, non-HDL-C, and apo B. TG levels were also substantially reduced, but not statistically significant in placebo-adjusted analyses.
Author Disclosures: Y. Qin: Employment; Significant; Pronova BioPharma - part of BASF. J. Hallén: Employment; Significant; Pronova BioPharma - part of BASF. T. Skjæret: Employment; Significant; Pronova BioPharma - part of BASF. E. Odden: Employment; Significant; Pronova BioPharma - part of BASF. D. Fraser: Employment; Significant; Pronova BioPharma - part of BASF. H. Nyheim: Employment; Significant; Pronova BioPharma - part of BASF. K. Cornelissen: None. J. Chiesa: None. S. Hustvedt: Employment; Significant; Pronova BioPharma - part of BASF.
- © 2014 by American Heart Association, Inc.