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Positive Results Reported for Nephropathy Drug Pyridoxamine (Pyridorin) in QT Study
A QT/QTc cardiac safety study has been successfully completed for pyridoxamine dihydrochloride (Pyridorin, NephroGenex, Inc.), an investigational treatment for diabetic nephropathy. This type of study assesses a drug’s risk of QT prolongation and its pro-arrhythmic potential, and is a standard component of all clinical development programs for new molecular entities.
Pyridoxamine showed no effect on the QT/QTc interval at the expected therapeutic dose of 300 mg and at a higher dose of 1,200 mg. In previous phase I and phase II studies, pyridoxamine had no effect on the QT/QTc interval in patients with diabetic nephropathy.
Diabetic nephropathy is a chronic, degenerative disease of the kidney caused by diabetes. Approximately 6 million patients have diabetic nephropathy in the U.S. (approximately 33% of diagnosed diabetics), and this population is expected to grow. Patients with diabetic nephropathy ultimately progress to end-stage renal failure requiring dialysis, or to death. No adequate treatments are currently available for this disease.
Pyridoxamine dihydrochloride is a small-molecule drug candidate with a chemical structure similar to, but distinct from, vitamin B6 (pyridoxine). Unlike vitamin B6, pyridoxamine is regulated as an investigational drug candidate by the FDA.
The compound consists of a pyridine ring containing hydroxyl, methyl, aminomethyl, hydroxymethyl, and phenol substituent groups. The phenol at position 3 and the aminomethyl group at position 4 of its ring provide pyridoxamine with inhibitory activities against pathogenic oxidative chemistries. These activities reduce the formation of advanced glycation endpoint products, which are known to damage the structure and function of proteins and lead to vascular damage. Microvascular injury is the fundamental cause of diabetic nephropathy.
In phase II clinical studies, pyridoxamine slowed the progression of nephropathy in diabetic patients with mild or moderate kidney disease and in those with advanced disease receiving an established regimen of standard of care.