Molecule CX717 Has Positive Effects In Opiate-Induced Respiratory Depression In A Phase IIa Clinical Study

Main Category: Respiratory / Asthma
Also Included In: Pain / Anesthetics
Article Date: 07 Aug 2008 - 0:00 PDT

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Cortex Pharmaceuticals, Inc. (AMEX: COR - News) reported that top-line data from its first Phase IIa study in opiate-induced respiratory depression (RD) demonstrated that a single oral dose of 2100mg of AMPAKINE® CX717 achieved statistical significance over placebo on the primary endpoint measure. These results are being presented at the Bank of Montreal Capital Markets Focus on Healthcare Conference in New York City on Wednesday morning, August 6, 2008 at 9:30AM (EDT) by Dr. Roger G. Stoll, President & CEO of Cortex. This placebo controlled, double-blind, randomized two-way crossover trial (RD-02) was performed by Parexel's clinical research unit in Europe. In this study, eight (8) volunteers per dose group each received either 900mg, 1500mg, or 2100mg of CX717 or matching placebo that was orally administered two hours before each subject received an intravenous infusion of the opiate agonist, alfentanil. The primary performance measures were derived from a CO2 re-breathing procedure that measured the breathing response of the subject to increased CO2 levels in the presence of alfentanil. The primary measure, the minute expiratory volume (VE) at 55mgHg CO2 (VE55), was reversed by 2100 mg CX717 in comparison to placebo (p<0.03).

No reliable responses were seen in the 900mg and 1500mg CX717 groups, but procedural problems were detected by the Data Safety Monitoring Board (DSMB) for this study, which was authorized by the protocol to monitor safety and responses on an interim basis. Corrective procedural changes were instituted before the initiation of the last group of subjects in the 2100mg segment of the study.

"While we initiated this study using oral doses of CX717 and had only eight subjects per treatment group, we were pleased to obtain statistical significance using such small study groups," said Dr. Roger Stoll the CEO of Cortex. The primary objective was to simply verify that the mechanism, which was seen functioning in animal studies, would also be operative in humans. Substantial investments were required to develop an intravenous dosage form of CX717, including formulation development and stability studies for such a dosage form as well as two species toxicology trials. The Company now feels that it can proceed with such studies. Cortex recently received verification of three months of accelerated stability for the experimental intravenous formulation of CX717 and plans to initiate toxicology trials in the fourth quarter 2008.

A second respiratory depression study has been performed by a group in Frankfurt, Germany. This study uses a single dose of 1500mg of CX717 and focuses on both the respiratory depression and the analgesic effects associated with alfentanil. The analysis of the data has been initiated and related results should be reported within a few weeks. Studies of CX717 in animal models by Dr. John Greer at the University of Alberta have shown that the AMPAKINE drugs do not interfere with the analgesic effects of opiates.

Cortex continues to advance other AMPAKINE compounds, particularly those newer compounds that have potential patent lives to 2028. It will also be reported at the BMO Capital Markets conference that Cortex has initiated human phase one safety and kinetic trials with CX1739 in normal volunteers. Assuming successful Phase I human trials with this compound, the Company plans to rapidly pursue the Attention Deficit-Hyperactivity disorder indication for CX1739 in the second half of 2009. The Company will also report on an initial animal trial with CX1942, a unique pro-drug analog of another low impact AMPAKINE drug that is highly water soluble, ideally suited for an intravenous dosage form. This compound rapidly hydrolyzes to the parent AMPAKINE drug in vivo. CX1942 has shown exceptionally rapid results in reversing respiratory depression due to intravenously administered fentanyl in rats. The Company plans to initiate toxicology studies with this unique analog during the last quarter of 2008.

High impact AMPAKINE compounds from recent patent applications are also being advanced with a focus on neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, as well as orphan drug indications like Huntington's and Fragile X disease.

The conference presentation will be webcast and available for a period of thirty days after the conference by logging on to http://www.bmocm.com/conferences/2008healthcare/default.aspx.

Cortex Pharmaceuticals, Inc.

Cortex, located in Irvine, California, is a neuroscience company focused on novel drug therapies for treating psychiatric disorders, neurological diseases and brain mediated breathing disorders. Cortex is pioneering a class of proprietary pharmaceuticals called AMPAKINE compounds, which act to increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer's disease. Many psychiatric diseases, including schizophrenia, occur as a result of imbalances in the brain's neurotransmitter system. These imbalances may be improved by using the AMPAKINE technology. Cortex has an alliance with Schering-Plough Corporation who acquired Cortex's former partner N.V. Organon in November 2007. As a result of this acquisition, Schering-Plough has two AMPAKINE Phase II compounds Org24448 and Org 26576 for the treatment of schizophrenia and depression. In December 2006 Cortex terminated the research collaboration with Servier enabling Cortex to pursue the use of AMPAKINE compounds in the treatment of neurodegenerative diseases on a global basis. Servier retained the right to select up to three compounds developed during the collaboration for further development for the treatment of neurodegenerative diseases. Cortex may receive additional milestones and royalties if either Organon or Servier is successful in developing and commercializing AMPAKINE compounds. For additional information regarding Cortex, please visit Cortex Pharmaceuticals' website at http://www.cortexpharm.com.

Forward-Looking Statement

This press release contains forward-looking statements concerning the Company's research and development activities. The success of such activities depends on a number of factors, including the risks that the Company's proposed compounds may at any time be found to be unsafe or ineffective for the indications under pre- clinical or clinical tests and that such studies may at any point be suspended or take substantially longer than anticipated to complete. The forward-looking statements are necessarily subject to risks and uncertainties, all of which are difficult or impossible to predict accurately and many of which are beyond the control of Cortex, all as more fully described in the risk factors and other matters set forth in Cortex's Annual Report on Form 10-K for the year ended December 31, 2007, and Cortex's other filings with the Securities and Exchange Commission, As discussed in the Company's Securities and Exchange Commission filings, the Company's proposed products will require additional research, lengthy and costly clinical testing and regulatory approval. AMPAKINE compounds are investigational drugs and have not been approved for the treatment of any disease. Cortex disclaims any intent or obligation to update any forward-looking statements.

Cortex Pharmaceuticals, Inc.