Resverlogix Corp., a clinical stage cardiovascular company with an epigenetic platform technology that modulates protein production, has initiated an exploratory phase II clinical trial in patients with pre-diabetes mellitus to examine the effects of RVX-208 and ApoA-I production on glucose metabolism. Twenty patients will be enrolled in Australia, with data expected in the first half of 2014.

The trial is conducted in collaboration with Baker IDI Heart & Diabetes Institute in Melbourne, Australia, and it will examine insulin secretion, insulin sensitivity and other parameters of importance in individuals with pre-diabetes mellitus.

The foundation of this trial builds upon the actions of RVX-208 and the knowledge that this compound triggers a key epigenetic pathway resulting in enhanced ApoA-I protein production to raise the body's level of functional HDL particles. The effect of newly created ApoA-I/HDL may help to preserve pancreatic cells that make and secrete insulin. Increased abundance of insulin in subjects with pre-diabetes mellitus may prevent or substantially delay the progression towards diabetes mellitus. The estimated trial expense will be less than $1MM CDN with an approximate split in costs of 50/50 between Resverlogix and the Baker IDI Heart & Diabetes Institute.

"Diabetes mellitus is the most common endocrine disease in the world," said Dr Norman Wong, chief scientific officer, Resverlogix. "The prevalence of this disease is rising at epidemic rates. A primary defect in diabetes mellitus is that the patient's pancreas cannot provide enough insulin for the body, thus leading to increased blood glucose levels. Diabetes mellitus can lead to severe sequelae such as kidney disease, heart disease, disorders of the nerves and blindness. Altering the natural course of the disease could be of great benefit to patients.

"This planned exploratory trial is an important prerequisite to potentially expand the indications for RVX-208 to type 2 diabetes mellitus."

RVX-208 is a first-in-class, small molecule that inhibits BET bromodomains. It is currently in clinical study for the treatment of atherosclerosis. RVX-208 functions by removing atherosclerotic plaque via reverse cholesterol transport (RCT), the natural process through which atherosclerotic plaque is transported out of the arteries and removed from the body by the liver. RVX-208 increases production of ApoA-I, the key building block of functional high-density lipoprotein (HDL) particles and the type required for RCT. These newly produced functional HDL particles are flat and empty and can efficiently remove plaque and stabilize or reverse atherosclerotic disease. RVX-208 is currently being evaluated in phase IIb studies for its ability to reverse and/or stabilize atherosclerotic disease. The drug candidate also has the potential to treat other indications, including neurodegenerative disorders and diabetes mellitus.