期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 57, 期 9, 页码 1111-1119出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2010.11.015
关键词
apoA-I; coronary artery disease; high-density lipoprotein; prevention; risk factors
资金
- AstraZeneca
- Novartis
- Resverlogix
- Eli Lilly
- Anthera Pharmaceuticals
- LipoScience
- Abbott
- GlaxoSmithKline
- Merck
- Sanofi-Synthelabo
- Schering-Plough
- Takeda
- Roche
- Karo Bio
- Genzyme
- ISIS
- Amarin
- Boehringer Ingelheim
- Anthera
- Cerenis
- Sankyo
- Sanofi-Aventis
Objectives The purpose of this study was to investigate the safety, tolerability, and efficacy of RVX-208, the first oral agent designed to enhance apolipoprotein (apo) A-I synthesis. Background No agent that selectively induces synthesis of apoA-I has reached an advanced stage of clinical development. Methods A total of 299 statin-treated patients with coronary artery disease were treated with placebo or with RVX-208 at a dose of 50, 100, or 150 mg twice daily for 12 weeks. Changes in lipid-related biomarkers, in addition to safety and tolerability, of RVX-208 were investigated. Results For each dose of RVX-208, individual pairwise comparisons of apoA-I changes with placebo, the primary end point, did not achieve statistical significance. However, treatment with RVX-208 was associated with a dose-dependent increase in apoA-I levels by up to 5.6% (p = 0.035 for trend). Administration of RVX-208 resulted in significant increases in levels of high-density lipoprotein cholesterol (HDL-C) ranging from 3.2% to 8.3% (p = 0.02), and large HDL particles increased by 11.1% to 21.1% (p = 0.003). ApoA-I levels increased rapidly from 8 to 12 weeks, suggesting that peak pharmacological effect has not been achieved by the end of the 12-week study. Transient and reversible elevations in liver transaminases > 3 times the upper limit of normal were observed in 18 patients treated with RVX-208, with no associated increase in bilirubin levels. Conclusions Administration of RVX-208 for 12 weeks was associated with increases in apoA-I, HDL-C, and concentration of large HDL particles, consistent with facilitation of cholesterol mobilization. Maximal increases in apoA-I may require longer exposure. An increase in liver enzymes was observed with active treatment. (Clinical Trial for Dose Finding and Safety of RVX000222 in Subjects With Stable Coronary Artery Disease; NCT01058018) (J Am Coll Cardiol 2011; 57: 1111-9) (C) 2011 by the American College of Cardiology Foundation
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