A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 2b Study to Evaluate the Safety and Efficacy of Pyridorin (Pyridoxamine Dihydrochloride) in Patients With Nephropathy Due to Type 2 Diabetes

Diabetic kidney disease afflicts about 20% of all diabetics and is the major cause of end-stage renal disease (ESRD). There are an estimated 1.2 million diabetic overt nephropathy patients in the US, and approximately 5.1 million diabetic patients exhibiting signs of developing kidney disease.

Hyperglycemia-induced microvascular disease is the fundamental cause of diabetic kidney disease. More specifically, hyperglycemia perturbs metabolic pathways, particularly in tissues that do not regulate intracellular glucose levels. This favors a broad range of pathogenic oxidative chemistries including the formation of advanced glycation end-products (AGEs), toxic carbonyls, and reactive oxygen species (ROS) that are considered to be the principal causative factors in the development of diabetic microvascular disease.

Pyridorin™ has been shown to inhibit AGE formation and to scavenge ROS and toxic carbonyl compounds in extensive in vitro studies. The therapeutic potential of Pyridorin™ has been demonstrated in vivo by extensive preclinical studies that have been carried out in a number of independent laboratories by prominent investigators. In addition, Pyridorin™ has demonstrated a significant treatment effect in slowing the progression of diabetic nephropathy in two Phase 2 clinical trials. Thus, a solid scientific rationale and clinical evidence exists for the application of Pyridorin™ therapy to slow the progression of diabetic kidney disease.

NephroGenex is initiating a new Phase 2b clinical trial (PYR-210) that is evaluating the safety and efficacy of Pyridorin™ in slowing the progression of overt nephropathy in patients with type 2 diabetes. This trial incorporates the latest discussion with the FDA regarding the use of an approvable surrogate marker that would be subsequently confirmed with hard clinical endpoints.

In this double-blind, placebo-controlled study, eligible type 2 diabetic patients with overt nephropathy will be treated for one year with bid doses of either Pyridorin™ 150 mg, Pyridorin™ 300 mg, or placebo. The primary endpoint in the study is the change in serum creatinine (SCr) from baseline after 1 year of therapy. Secondary 1-year endpoints include the slope of SCr, the change in protein/creatinine ratio (PCR) derived from 24-hour urine collections, and the change from baseline and slope of serum cystatin C.