Re: Ampakine CX1739? over the counter nootropics?

[JimC.]

Cortex in the USA had CX!&#( turned down as an ADD drug by the regulator, and they decided to back off. Clinical Developments

from their site…see latter paragraphs…

Cortex has completed several Phase I human safety and tolerability studies with CX717 involving over 100 subjects, including elderly subjects, tested at doses up to 1600mg per day. The plasma half-life of CX717 was found to be 9-10 hours, and CX717 exhibited an excellent safety and tolerability profile. This was followed by the initiation of six Phase IIa studies, three of which have been completed. The first CX717 Phase IIa human study was in 16 subjects and evaluated three doses of CX717 (100mg, 300mg, 1000mg) and matching placebo in a double-blinded design in normal subjects that had been sleep deprived for 28 hours. CX717 was found to be safe and well tolerated by all subjects in the sleep deprivation study, and improved alertness with the 300mg and 1000mg doses. Some cognitive tests in this same study also provided early indications of positive responses. In all doses of CX717, there was evidence of cerebral arousal without systemic activation, e.g., no increases in blood pressure or heart rate, which are commonly seen with caffeine, amphetamines and other stimulants.

The second completed Phase IIa study was a 48-subject trial evaluating excessive daytime sleepiness in a shift work simulation supported and conducted by the Defense Advanced Research Projects Agency (DARPA). In this study, CX717 did not demonstrate a significant effect on cognitive performance, although EEG studies confirmed an effect on the sleep architecture, consistent with the first sleep deprivation study.

The third Phase IIa study enrolled 68 moderate to severe adult ADHD patients in a randomized, double-blind, placebo-controlled, two-way crossover design study performed at seven U.S. sites. The primary outcome measure was the ADHD Rating Scale (ADHD-RS) which evaluated both the inattentiveness and hyperactivity symptoms. The overall ADHD-RS score showed a statistically significant effect (p<0.002) in the 800mg twice-daily dose group, with patients demonstrating a statistically significant effect on both the hyperactivity (p=0.013) and inattentiveness subscale (p=0.031) as compared to placebo. CX717 was well tolerated, and there were no serious adverse events or other significant safety concerns with either dose. This data provides the first study demonstrating Proof-of-Concept in humans with an AMPAKINE compound for the treatment of adult patients with ADHD. The Company had planned to pursue a larger Phase IIb study in adult patients with ADHD because of the advantages over the current treatments shown below:

In March 2006, CX717 was put on clinical hold by the FDA’s Division of Neurology Drug Products due to a finding in a preclinical toxicology study. Further studies by Cortex suggested that the histopathology changes seen at very high doses of CX717 in preclinical toxicology studies were due to a post mortem artifact that occurs during the tissue fixation process. In October 2007, the Neurology Division of the FDA allowed Cortex to resume enrollment of the Phase IIa Alzheimer’s disease study. The design of this study is to assess two different CX717 doses in mild-to-moderate Alzheimer’s disease (AD), with each patient receiving psychometric tests and PET scans at different time intervals while on active drug or placebo. However, the FDA’s Division of Psychiatry Products did not give approval for a clinical study in adult patients with ADHD.

In May 2007, Cortex completed a Patent License Agreement with the University of Alberta, BC for the worldwide use of AMPAKINE compounds to reverse or prevent respiratory depression induced by therapeutic doses of opiate analgesic and sedative anesthetic agents, including barbiturates without the loss of the desired therapeutic; analgesia and sedation from these respective classes of drugs commonly utilized in the majority of surgical cases performed in both hospital settings and during out –patient surgical procedures. Based on data from the use of CX717 and other AMPAKINE compounds in several animal species, AMPAKINE compounds may be broad spectrum reversal agents for multiple classes of drugs that depress central nervous system activity and lead to respiratory depression events that can be life threatening. Milder forms of breathing cessation, such as central and obstructive sleep apneas could potentially constitute additional treatment targets for the Company to pursue.

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