Replies to post #1702 on RespireRx Pharmaceuticals Inc (fka RSPI)

[K-G]

Aiming4,
If I read between the lines correctly, Dr. Stoll expects that if there are no additional issues found with CX-717, and the toxicology assessments show a suitable safe dosing range, then they would conduct some TBD AD efficacy tests, the results of which would be available mid-year 2007 at the earliest. He also said he does not expect any AD deals to be made in the absence of solid efficacy data.

[neuroinv]

<<In other words, might CX-717 still be viable for AD development even with the histo issue, since the AD doses will be below the threshold that triggers those cellular changes?>>

Any clinical dose would be below that level. I just want to reiterate the magnitude of doses we are talking about here: Somewhere around 1gm/kg the cellular 'signal' starts. Now Stoll is a pharmacologist by training, so he didnt want to embrace a simplistic comparison, but I think in this case, simplicity is instructive:

75 kilo human/1gm per kilo/75 grams per day--or about 1/6 of a pound of CX717.

If the ADHD dose were 1000 mg per day, which is in the 10-20mg/kg range Stoll mentioned, that would mean the toxic dose is 75 times higher--a therapeutic index of 75. It is of course possible that metabolic differences--or species-specific production of metabolites, could skew this one way or another. But this is a pretty good therapeutic index. Try taking 75 Wellbutrin (three can cause seizures)....

A key question which I neglected to ask--focusing on these high doses--was the dose that the first monkey had taken, the one which triggered this whole. Ironically, there is apparently some question of whether part of the histopathology procedure itself could have produced that result as an artifact--but setting that aside: I know that Stoll had said that the summer studies pushed the maximum dose far higher than before. If it was 10x higher, that would mean that the first monkeys received a dose 7.5X greater than the human dose--one out of twelve showed this anomaly....

Bottom line--it's going to take a lot longer to clear this up than we thought. Like the announcement that Stoll made in mid-Sept, he could conceivably make a comment during January about the results of the three month tests--was the 'signal' seen--or not. If not, the likelihood of the dose range being allowed to ris to ADHD trial levels would be high. If it is seen--and these monkeys are being given high doses, the question will be--at what level of dose did they show up, and are they associated with a metabolite not seen in man? Clearly the FDA is being extremely fussy about the therapeutic index--would they accept something with an index of 20, of 15? If not, then they are holding the drug to a much higher standard than are the stimulants (you don't want to see what would happen to someone taking 20 Ritalin, or 20 Wellbutrin....or 20 Adderall....) or the tricyclic antidepressants--or Tylenol for that matter.

NeuroInvestment