Replies to post #34986 on RespireRx Pharmaceuticals Inc (RSPI)

[davidal66]

You might get a reduction in periods of apnea which I think is defined for apnea criteria as not breathing for greater than 10 seconds or less significant periods of time less than 10 seconds. "Positive" responses would, by definition, show less arousals where the EEG reverts back to periods of drowsiness and even wakefulness during apneic periods. Less severe are briefer periods of micro-arousals. So, these are EEG correlates of good, deep sleep on the one hand versus apnea leading to more periods of the wake sleep since the patient is waking up or almost waking up throughout the night. In a sense, they are actually sleep deprived since they never obtain(or more importantly)sustain long periods of deep or stage III/IV sleep which is the so called 'restorative sleep' and these folks are chronically sleepy.

So on the clinical front you would look at periods of apnea, count 'em up and score them in terms of length of episode and degree, if any, of oxygen levels going down. Then you look at the epochs of sleep and determine periods of arousal and micro-arousals. You look at the EMG on the leg for level of muscle activity which are different in deep sleep, light sleep and REM sleep. In more detailed labs you even look at the gastric ph level since reflux can lead to "sleep apnea" in a sense as well or at least mimic it.

So these are the broad things that are looked at. My fear subjectively might be it worked, but at a cost of insomnia which would be expected to be a side effect of ampakines, possibly rendering the results interesting but not clinically relevant. If insomnia altered the sleep patterns on the test day where CX1739 is given, the "adjusting" your clinical settings, degree of apnea would be quite difficult to sort out. I suspect this is not an issue because as a side effect, it might have been recognized at the get go.

So if CX1739 works you might expect to see 1. less severe and fewer periods of apnea, 2. Lack of hypoxia so the O2 level does not decline, 3. a more 'smooth' sleep pattern from drowsiness to a more robust continuous stage IIi/IV deep sleep followed by REM with d. subjectively an improved sense of wakefulness during the day without feeling as sleepy....

[gfp927z]

Neuro, I wonder if the 40% variability allowed in baseline readings (between baseline nights 1 and 2) may have doomed this trial from the start? That's a big hurdle to overcome in order to demonstrate a drug effect.