MBX-8025, A Novel Peroxisome Proliferator Receptor-δ Agonist: Lipid and Other Metabolic Effects in Dyslipidemic Overweight Patients Treated with and without Atorvastatin
| Autor: | Brian K. Roberts, Thomas W. Littlejohn, Yun-Jung Choi, David B. Karpf, Ronald M. Krauss, Sue Naim, Boris Kerzner, Wang Xueyan, Harold E. Bays, Sherwyn Schwartz |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty Apolipoprotein B medicine.drug_class Endocrinology Diabetes and Metabolism Atorvastatin Clinical Biochemistry Peroxisome proliferator-activated receptor Context (language use) Pharmacology Placebo Biochemistry Endocrinology Double-Blind Method Internal medicine medicine Humans Pyrroles PPAR delta Aged Dyslipidemias chemistry.chemical_classification biology business.industry Biochemistry (medical) MBX-8025 Middle Aged Overweight medicine.disease Lipids C-Reactive Protein Treatment Outcome Liver chemistry Heptanoic Acids biology.protein Drug Therapy Combination Female lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors business Dyslipidemia medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 96:2889-2897 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2011-1061 |
| Popis: | 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.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.This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites.This study evaluated 181 overweight men and women with mixed dyslipidemia.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.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.Compared to placebo, MBX-8025 alone and in combination with atorvastatin significantly (P0.05) 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.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. |
| Databáze: | OpenAIRE |
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