DARA's DB959 shows promise against type 2 diabetes

A new peroxisome proliferator activated receptor agonist currently in development, DB959, will most likely be administered orally once a day, according to a presentation made by researchers recently at the American Diabetes Association's 71st Scientific Sessions. This would make DB959 unique among medications that treat people with type 2 diabetes. More convenient, effective drugs for diabetes are essential since almost 26 million adults in this country now have the disease, and the CDC has warned that diabetes could affect a third of all adult Americans by 2050. Many of these people have uncontrolled disease; the convenience of taking one effective pill a day could clearly be beneficial.

Well tolerated at high doses

A recently completed escalating dose study by DARA BioSciences, Inc. has tested the single-dose safety, tolerability, and pharmacokinetics of DB959. This first human trial was a randomized, placebo-controlled, double-blind study, and it enrolled 70 healthy volunteers aged 18 to 45 in groups of eight participants each. The first group of volunteers was given 2 mg of DB959. After ensuring that dose was well-tolerated, another group was given 5 mg, the next group was given 10 mg, and then subsequent groups received doses escalating up to 200 mg per day. Both active and placebo groups tolerated the drug equally at all doses; the few adverse effects that were shown were mild and not dose related. The researchers monitored the vital signs of study participants, measured clinical chemistries, performed physical examinations, obtained ECGs and checked their weights regularly to ascertain the presence of edema. Study participants had no moderate, severe or serious adverse reactions, and had no clinically significant changes in vital signs, laboratory parameters, physical exam, nor any ECG changes.

The pharmacokinetic parameters of the drug were consistent with once a day dosing. The drug's half-life ranged from 14.8 to 19.9 hours over the tested dose range. Other measurements revealed that the drug was not excreted unchanged in urine, and the examination of a possible food effect revealed that a high fat meal only slightly delays the drug's absorption.

According to Mary K. Delmedico, Ph.D. and her co-authors, DB959 continues to show promise. In addition to demonstrating its long half-life, the current study found that the maximum tolerated single dose of the drug is over 200 mg, which is approximately 10 times the anticipated therapeutic dose range.

Unique PPAR

DB959 is in a different chemical class from the PPAR medications currently on the market, and the drug has demonstrated a favorable effect on blood lipids as well as blood sugar; it raises HDL while lowering both triglycerides and blood glucose. Dr. Delmedico said, "This is an important finding, since most people with diabetes don't have good control of their lipids. Also, we've seen from previous studies that DB959 appears to have less liability concerning weight gain than other PPARs - something we'll continue to study in Phase 2."