DiObex Begins Phase 2b Trial Of Type 2 Diabetes Drug
DiObex has begun dosing patients in a Phase 2b clinical trial of DIO-902, a novel cortisol synthesis inhibitor being studied for the treatment of type 2 diabetes mellitus (T2DM).
The Phase 2b multinational trial is a randomized, placebo-controlled, double-blinded study designed to evaluate the safety and efficacy of DIO-902 and to determine dosing for pivotal Phase 3 clinical studies. The primary efficacy endpoint being evaluated is the change in HbA1c, a key measurement of glycemic control, compared to placebo. Secondary endpoints include the change in total and LDL-cholesterol, and the change in blood pressure. Top line data from the trial is expected by the second half of 2008.
"The rollout of this multinational, multicenter trial demonstrates DiObex's ability to launch a major clinical program for the treatment of metabolic disease," CEO David Cory said. "With treatments for both type 1 and type 2 diabetes in mid-stage clinical study and additional indications under evaluation for DIO-902, DiObex is well positioned to move a strong pipeline of product candidates into the advanced stages of development."
The trial is being conducted at 20 centers across the United States, Australia and New Zealand. Approximately 200 patients will be treated for 16 weeks. Patients who are already on a stable dose of metformin will be randomized to receive placebo or one of three doses of DIO-902 once daily for 16 weeks, with the option of continuing on an open label extension for an additional six months of treatment.
Preclinical and clinical studies have suggested that a link exists between high cortisol levels and visceral adiposity, insulin resistance, and hyperglycemia -- common elements of T2DM and metabolic syndrome. There are no cortisol synthesis inhibitors on the market today, potentially making DIO-902 a first-in-category treatment.
"We are very encouraged by results of our earlier Phase 2a study that showed a trend toward improved glycemic control, as well as statistically significant reductions in levels of cholesterol and C-reactive protein that suggest DIO-902 could potentially lower the risk of heart disease," said Dr. Bernice Welles, Vice President of Development at DiObex. "DIO-902 could potentially give patients a way to manage their disease with fewer medications and, if ultimately approved, would be a valuable addition to the armamentarium of agents to help patients with type 2 diabetes."
DIO-902 is a cortisol synthesis inhibitor that is being developed as a therapy for glucose and cholesterol control in patients with T2DM. DIO-902 may also benefit hypercholesterolemia patients who fail to achieve treatment targets on current lipid medications or those who are statin intolerant. DIO-902 increases insulin sensitivity by lowering cortisol levels. The primary mechanism of action is via inhibition of the 11-beta-hydroxylase
enzyme, the terminal step in cortisol synthesis in the adrenal gland. DIO-902 has also been shown to lower total and LDL-cholesterol by inhibiting 14-alpha-demethylase, a key enzyme in cholesterol synthesis. DIO-902 is the levdex enantiomer of ketoconazole. Pre-clinical and clinical evidence are supportive that DIO-902 may be safer and more effective than racemic ketoconazole.