MBX-8025, a novel peroxisome proliferator receptor-δ agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without …

HE Bays, S Schwartz, T Littlejohn III… - The Journal of …, 2011 - academic.oup.com
HE Bays, S Schwartz, T Littlejohn III, B Kerzner, RM Krauss, DB Karpf, YJ Choi, X Wang…
The Journal of Clinical Endocrinology & Metabolism, 2011academic.oup.com
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 …
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.
Oxford University Press