Phase 2a Data Of DIO-902 Improved Glycemic Control And Significant Reductions Of LDL-Cholesterol
DiObex presents of top line data of its phase 2a study of DIO-902, a first-in-category Cortisol Synthesis Inhibitor for the treatment of type 2 diabetes.
Results of the two week placebo-controlled, dose-ranging study demonstrated that in patients treated with DIO-902 there was a trend toward improved glycemic control as measured by HbA1c, fructosamine and fasting blood glucose, as well as significant dose-dependent reductions in total and LDL- cholesterol. Mean levels of C-reactive protein (a marker of cardiovascular inflammation) were also significantly reduced in a dose-dependent fashion. Besides glycemic control, the additional benefits provided by DIO-902 may allow type 2 diabetes patients to manage their disease with fewer medications.
The data was presented at the 67th Annual Scientific Sessions of the American Diabetes Association (ADA) in Chicago, IL by Sherwin Schwartz, MD, lead investigator from the Diabetes and Glandular Disease Clinic of San Antonio, Texas. In his oral presentation, Dr. Schwartz detailed the results of the recently completed multi-center, randomized, placebo-controlled trial of DIO-902 in patients with type 2 diabetes.
"DIO-902 was well tolerated and we saw early signals of improvements in glycemic control," said Dr. Schwartz. "In addition, DIO-902 also showed early indications of potential to reduce the risk of heart disease through the significant reduction of LDL-cholesterol by as much as 46 percent at the highest dose studied. The prospect of a single therapeutic which has the potential to address multiple co-morbidities is very exciting."
DIO-902 is an oral, once-daily drug being developed for the treatment of type 2 diabetes. It is a single enantiomer of racemic ketoconazole which suppresses cortisol production by inhibiting the 11 beta hydroxylase enzyme, the terminal step in the adrenal synthesis of cortisol. This novel mechanism of action makes DIO-902 a first-in-category cortisol inhibitor.
"Our unique approach to inhibition of cortisol synthesis offers the potential to address one of the underlying causes of type 2 diabetes, as well as multiple co-morbidities associated with both the disease, and its precursor, metabolic syndrome," said David A. Cory, Chief Executive Officer of DiObex, Inc. "DIO-902 offers patients the promise of effectively managing glycemia and lipids with a single medication. We are excited about the preliminary data generated to date and are rapidly progressing DIO-902 to the next stage of clinical development."
Data from various preclinical, epidemiological and clinical studies have suggested that a link exists between high cortisol levels and visceral adiposity, insulin resistance, and hyperglycemia -- common elements of the metabolic syndrome and type 2 diabetes.
The two-week trial with DIO-902 enrolled 37 patients with type 2 diabetes who were randomized to placebo, three different doses of DIO-902 ( 200 mg, 400 mg and 600 mg) or ketoconazole. Patients were either drug naove or on metformin, and had lipid-lowering agents washed out for at least 21 days prior to the first dose of the study drug. No serious adverse effects related to the study drug were reported. Liver function tests were carefully monitored, and no clinically meaningful changes were observed in any of the treated subjects. In fact, a number of subjects enrolled with mild transaminase elevations normalized during the two week treatment.
DiObex will conduct a multi-center, 16-week, phase 2b dose-ranging study with DIO-902; this study is scheduled to start enrolling patients in three countries in mid-2007.