The Phase II study was a randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of MBX-8025, both alone and in combination with atorvastatin (marketed as Lipitor), over an eight-week treatment period.
The trial enrolled a total of 183 overweight or obese patients with high cholesterol and triglycerides, of whom 173 completed the entire eight weeks of treatment. The trial was composed of six groups of approximately 30 patients, including two different doses of MBX-8025 (50mg and 100mg), both alone and in combination with Lipitor (20mg), placebo and Lipitor only.
Treatment with MBX-8025 was well tolerated, with no reports of drug-related serious adverse events and no emerging safety findings as compared to placebo and/or Lipitor. Patients treated with MBX-8025 alone experienced an approximate 30% reduction in triglycerides (p < 0.0001) and 20% drop in low-density lipoprotein (LDL) cholesterol (p < 0.0001) versus placebo after eight weeks of treatment. In addition, MBX-8025 raised high-density lipoprotein cholesterol by approximately 8% (50mg; p = 0.068) and 12% (100mg; p = 0.0045). The triglyceride-lowering effect of MBX-8025 was observed in combination with Lipitor without raising LDL cholesterol. Additionally, MBX-8025 selectively and substantially depleted the small, dense LDL cholesterol particles, both alone and in combination with Lipitor. These particles convey an independent cardiovascular risk and their depletion represents an added benefit to the LDL lowering itself. Patients treated with MBX-8025 also experienced decreases in fasting insulin and glucose (100mg; p = 0.01), consistent with improvements in insulin sensitivity. Also observed were significant decreases in gamma-glutamyl transpeptidase and alkaline phosphatase, suggesting a reduction in liver inflammation. MBX-8025 also appeared to have anti-inflammatory effects as indicated by reductions in high sensitivity C-reactive protein. David Karpf, chief medical officer of Metabolex, said: "MBX-8025 has the potential to become a next generation treatment for dyslipidemia that simultaneously improves multiple metabolic parameters with a resulting reduction in cardiovascular risk. In this Phase II study, MBX-8025 clearly demonstrated robust improvement of many cardiovascular risk factors without any apparent pattern of side effects associated with the drug."