Metabolex, a biopharmaceutical company focused on the discovery and development of proprietary new medicines for the treatment of metabolic diseases, reported positive results from two multiple ascending dose Phase 1 clinical trials of MBX-2982.
Reportedly, MBX-2982 is a selective, orally active agonist of G protein-coupled receptor 119 (GPR119) that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion. The company has recently completed two additional phase 1 studies of MBX-2982 in subjects with pre-diabetes. In both studies, subjects with either impaired fasting glucose or impaired glucose tolerance were enrolled.
The first study investigated the effect of four consecutive once daily doses (100 or 300mg) of MBX-2982 on the pharmacokinetics of the drug as well as its effect on glucose excursions following a mixed meal. In addition, the effect of MBX-2982 on insulin secretion during a graded glucose infusion was examined. MBX-2982 was absorbed and its exposure at both doses approximately doubled on day four compared to day one, consistent with a terminal half-life of 18 hour and supporting once daily dosing.
The data suggested that the glucose excursions following a mixed meal were reduced relative to baseline by 26% and 37%, respectively, for the 100 and 300mg cohorts. During the graded glucose infusions, the exposure to glucose was reduced relative to baseline by 11% and 18% for the 100 and 300mg cohorts, respectively. This was attributable to increases in insulin secretion. These results were all statistically significant.
However, the second study in a pre-diabetic population was a five-day placebo-controlled multiple ascending dose study with an alternate formulation of MBX-2982 at doses of 25, 100, 300 and 600mg. The effect of each dose on the glucose excursions following a mixed meal and an oral glucose challenge was investigated.
The company data from the study demonstrates that all four doses of MBX-2982 produced significant decreases in the glucose excursion following a mixed meal ranging from 34% to 51%. Similar decreases were also observed following the glucose challenge.
The company said that in both the studies, MBX-2982 was safe and generally well tolerated with no serious adverse events. These results provide continued clinical validation of the potential therapeutic benefits of MBX-2982 in the treatment of type 2 diabetes.
Harold Van Wart, CEO of Metabolex, said: “These studies show that we are ready to advance MBX-2982 into a phase 2a study in patients with type 2 diabetes with a wide range of doses. Based on the safety profile and continued encouraging effects on glucose levels, we look forward toward advancing MBX-2982 into its next stage of clinical development.”