Positive results from Naurex's Phase I clinical trial of GLYX-13 reported

Feb 10 2010

Naurex Inc., a clinical stage company developing innovative treatments for depression and other CNS disorders based on its novel glycine site functional partial agonist (GFPA) NMDA receptor modulators, today reported positive top-line results from its Phase I clinical trial of lead compound GLYX-13.  GLYX-13 is a GFPA selective modulator of the NMDA receptor.  It is initially being developed as a therapy for treatment-resistant depression in severely depressed patients.  In the Phase I trial, adverse events were similar for subjects receiving GLYX-13 and placebo and were all rated as mild.  There were no signs of the schizophrenia-like side effects associated with other NMDA receptor modulator drugs.

"These encouraging data in humans are consistent with the excellent safety profile demonstrated in preclinical studies of GLYX-13," said Ronald Burch, M.D., Ph.D., chief medical officer at Naurex.  "In view of the history of schizophrenia-like side effects caused by NMDA receptor modulators such as ketamine and CP-101,606, we are very pleased that there were no signs of these effects in this first trial of GLYX-13 in humans, even at higher doses than we expect would be required to provide antidepressant effects.  The pharmacokinetics of GLYX-13 also was encouraging, with similar or greater drug exposure seen in humans than in animals at the same doses.  These positive results will allow us to proceed to Phase II clinical trials in patients with severe treatment-resistant depression, a condition with an urgent need for better treatment options."

The GLYX-13 Phase I trial was a randomized, double-blind, placebo-controlled single ascending dose level study of the safety, tolerability and pharmacokinetics of four dose levels of GLYX-13 in healthy volunteers.  The primary outcome measures included observational and laboratory-confirmed safety parameters.  Schizophrenia-like side effects were specifically evaluated.

The efficacy of NMDA receptor glycine site functional partial agonists has been demonstrated in animal models in a number of CNS disorders, including major depressive disorder, neuropathic pain, schizophrenia, anxiety, Alzheimer's disease and other cognition disorders.  In these studies, GFPA modulators did not exhibit the schizophrenia-like side effects associated with NMDA receptor blockers that interact with other binding sites on the receptor complex.   In preclinical studies, GLYX-13 has demonstrated a wide therapeutic ratio (greater than or equal to 500:1) between efficacy and side effects, which is the largest therapeutic ratio of any reported molecule that interacts at the NMDA receptor.  Preclinical studies also showed that the antidepressant effects of GLYX-13 were evident within 20 minutes and demonstrated a lasting antidepressant effect of at least four days' duration after administration of a single dose.  In these studies, GLYX-13 affected both positive and negative symptoms of depression-like states in animals.