MBX-8025, A Novel Peroxisome Proliferator Receptor-δ Agonist: Lipid and Other Metabolic Effects in Dyslipidemic Overweight Patients Treated with and without Atorvastatin

• Published in: The journal of clinical endocrinology and metabolism Vol. 96; no. 9; pp. 2889 - 2897
• Main Authors: Bays, Harold E., Schwartz, Sherwyn, Littlejohn, Thomas, Kerzner, Boris, Krauss, Ronald M., Karpf, David B., Choi, Yun-Jung, Wang, Xueyan, Naim, Sue, Roberts, Brian K.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.09.2011; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Aged; Agonists; Apolipoprotein B; Apolipoproteins; Arteriosclerosis; Atorvastatin; Atorvastatin Calcium; Biological and medical sciences; Body weight; C-reactive protein; C-Reactive Protein - metabolism; Cholesterol; Clinical trials; Double-Blind Method; Drug Therapy, Combination; Dyslipidemia; Dyslipidemias - complications; Dyslipidemias - drug therapy; Dyslipidemias - metabolism; Endocrinopathies; Enzymes; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Heptanoic Acids - pharmacology; Heptanoic Acids - therapeutic use; High density lipoprotein; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Lipids; Lipids - blood; Liver; Liver - drug effects; Liver - metabolism; Low density lipoprotein; Male; Medical sciences; Metabolic syndrome; Middle Aged; Obesity; Overweight; Overweight - complications; Overweight - drug therapy; Overweight - metabolism; Patients; Peroxisome proliferator-activated receptors; Placebos; PPAR delta - agonists; Proteins; Pyrroles - pharmacology; Pyrroles - therapeutic use; Research (statistical design); Self efficacy; Statins; Treatment Outcome; Triglycerides; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Women; Agonist; Body weight; Lipids; Hypocholesterolemic agent; Peroxisome proliferator; Overweight; HMG-CoA reductase inhibitor; Dyslipemia; Nutritional status; Biological receptor; Human; Obesity; Nutrition; Enzyme; Nutrition disorder; Enzyme inhibitor; Patient; Metabolic diseases; Corporal biometry; Statin derivative; Treatment; Metabolic activation; Atorvastatin; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Endocrinology; Antilipemic agent
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2011-1061

Context:Preclinical and clinical studies suggest that peroxisome proliferator-activated receptor (PPAR)-δ agonists favorably affect multiple metabolic parameters that are otherwise proatherogenic, many that are not optimally managed with statins alone.Objective:The aim of this study was to evaluate the effects of MBX-8025 (a novel PPAR-δ agonist) on lipid and other metabolic parameters associated with increased atherosclerotic risk, administered alone and in combination with atorvastatin.Design and Setting:This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites.Participants:This study evaluated 181 overweight men and women with mixed dyslipidemia.Intervention(s):Subjects were administered once daily placebo, atorvastatin 20 mg, or MBX-8025 at 50 or 100 mg alone or combined with atorvastatin for 8 wk.Main Outcome Measures:The main efficacy measures included change from baseline in apolipoprotein B-100, lipid levels, high-sensitivity C-reactive protein, and additional metabolic parameters, as well as the effect on the metabolic syndrome and LDL particle size.Results:Compared to placebo, MBX-8025 alone and in combination with atorvastatin significantly (P < 0.05) reduced apolipoprotein B-100 20–38%, LDL 18–43%, triglycerides 26–30%, non-high-density lipoprotein cholesterol 18–41%, free fatty acids 16–28%, and high-sensitivity C-reactive protein 43–72%; it raised high-density lipoprotein cholesterol 1–12% and also reduced the number of patients with the metabolic syndrome and a preponderance of small LDL particles. MBX-8025 was safe and generally well-tolerated. MBX-8025 also reduced liver enzyme levels.Conclusion:MBX-8025, a novel PPAR-δ agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study.