Efficacy and Safety of a Novel Oral Inducer of Apolipoprotein A-I Synthesis in Statin-Treated Patients With Stable Coronary Artery Disease

摘要: Objectives The purpose of this study was to investigate the safety, tolerability, and efficacy RVX-208, first oral agent designed enhance apolipoprotein (apo) A-I synthesis. Background No that selectively induces synthesis apoA-I has reached an advanced stage clinical development. Methods A total 299 statin-treated patients with coronary artery disease were treated placebo or RVX-208 at a dose 50, 100, 150 mg twice daily for 12 weeks. Changes in lipid-related biomarkers, addition safety investigated. Results For each individual pairwise comparisons changes placebo, primary end point, did not achieve statistical significance. However, treatment associated dose-dependent increase levels by up 5.6% (p = 0.035 trend). Administration resulted significant increases high-density lipoprotein cholesterol (HDL-C) ranging from 3.2% 8.3% 0.02), large HDL particles increased 11.1% 21.1% 0.003). ApoA-I rapidly 8 weeks, suggesting peak pharmacological effect been achieved 12-week study. Transient reversible elevations liver transaminases >3 times upper limit normal observed 18 no bilirubin levels. Conclusions weeks apoA-I, HDL-C, concentration particles, consistent facilitation mobilization. Maximal may require longer exposure. An enzymes active treatment. (Clinical Trial Dose Finding Safety RVX000222 Subjects With Stable Coronary Artery Disease; NCT01058018 )