CX717
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| Routes of administration | By mouth, IV |
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CX717 is an
Approval process
In 2005 the
Also, in 2005, the
However, a 2006 study funded by DARPA found that CX717 did not improve cognitive performance in humans subjected to simulated night shift work.[6]
In early March 2006 Cortex reported that, in a small pilot Phase II study, CX717 had demonstrated positive clinical and statistical results on the primary endpoint, the
In April 2007 Cortex Pharmaceuticals submitted two large data packages to the FDA regarding CX717. One data set went to the FDA's Division of Neurology Drug Products for the treatment of Alzheimer's disease, while the other went to the Division of Psychiatry Products where the company filed a second CX717 IND for the treatment of ADHD. According to a Cortex Pharmaceuticals press release, the submitted data package "provides clear evidence that the specific histopathological changes seen in animal toxicology studies, which previously caused the FDA to put CX717 on clinical hold, is a postmortem fixation artifact and is not found in the tissue of the animal when it is still living".[7]
Roger G Stoll PhD, chief executive officer of Cortex, stated,
"When CX717 was removed from clinical hold on October 6, 2006 by the Neurology Division a dose was permitted for continuing a study in patients with Alzheimer's disease, but that dose was too low to permit the assessment of the drug in patients with ADHD. Further information was needed to better understand the cause of the histopathological changes. We now have a substantial data base which clearly documents the fact that the histological changes of concern occur postmortem when the fixative solution is used to prepare the slides of the tissue specimens."
However, in October 2007 the FDA denied Cortex's IND application for a Phase IIb study of CX717 for treatment of ADHD, based on the same animal toxicology results. Cortex responded by inactivating the application, although it will "continue its plans to develop CX717 for the acute treatment of respiratory depression (RD) and continue its study of CX717 in its Alzheimer's disease PET scan study. Cortex believes that the IND application previously filed with the Division of Neurology Products of the FDA for the treatment of Alzheimer's disease will not be affected by the actions of the DPP."[8] The company hopes that after the use of the compound in treating a high-risk acute condition is approved and well-established, the risks of longer-term use at higher doses, such as for treatment of ADHD, will be shown to be less than the FDA had concluded.
Use for reversal of respiratory depression
The relatively poor oral bioavailability and blood–brain barrier penetration of CX-717 ultimately led to Cortex abandoning development of the 800 mg oral formulation of CX-717 for ADHD,
Related AMPAkines
Other AMPAkine drugs from Cortex Pharmaceuticals such as
See also
References
- PMID 29277782.
- PMID 29253237.
- ^ US 6110935, Rogers GA, Marrs CM, "Benzofurazan compounds for enhancing glutamatergic synaptic responses", issued 29 August 2000, assigned to University of California.
- ^ PMID 18985324.
- PMID 16104830.
- ^ "Top-line findings on CX717 from the DARPA-sponsored shift work simulation study will be presented at sleep 2006 meeting". Cortex News & Events. Archived from the original on 2007-09-27. Retrieved 2007-10-21.
- ^ "Cortex's AMPAKINE CX-717 Toxicology Data Package Submitted to FDA". Archived from the original on 2009-01-06. Retrieved 2009-03-31.
- ^ "FDA's Psychiatric Division has Rejected Cortex's Request to Study CX717 in Phase IIb ADHD Study". Retrieved 2008-02-28.
- ^ "Untitled Document". Archived from the original on 2009-04-06. Retrieved 2009-07-20.
- PMID 19461299.
- ^ "Cortex Annual Shareholder Meeting Notification". Cortex Pharmaceuticals Press. 1 June 2009. Archived from the original on 23 February 2009. Retrieved 20 July 2009.
- PMID 20098731.
- S2CID 10723185.
- PMID 21636275.
- PMID 21636273.
- PMID 21889339.
Further reading
- Bast T, da Silva BM, Morris RG (June 2005). "Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and retrieval of one-trial place memory". The Journal of Neuroscience. 25 (25): 5845–5856. PMID 15976073.
- Arai AC, Kessler M, Rogers G, Lynch G (October 2000). "Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466". Molecular Pharmacology. 58 (4): 802–813. S2CID 6489143. Archived from the originalon 2005-03-07.
- "Cortex's AMPAKINE CX717 Toxicology Data Package Submitted To FDA". Cortex Pharmaceuticals press release. 18 April 2007. Archived from the original on 2007-09-27.