Replies to post #19647 on RespireRx Pharmaceuticals Inc (RSPI)

[enemem]

n=16 double-blind crossover design with 7 day washout in between.

Worst-case: no efficacy, no analgesia.

I think there's a decent chance that efficacy will be there, because they got significance with n=7. This is consistent with a robust effect, so I expect there to be some effect at 1500. Further, in this second study, efficacy is a bonus, since it's established that there's good efficacy at 2100 mg. The only thing that matters is analgesia, and even partial preservation of analgesia will warrant further development, given the dearth of alternatives.

They showed nothing pertaining to the lower dosages. This may be because the data were terrrible, but it is also possible that there were problems with the fentanyl administration, or with the rebreathing protocol.

[gfp927z]

Spyderboi, The 30% change you mentioned looks closer to 50%. Looking at slide 17, with placebo + alfentanil, the expiratory volume to reach a CO2 concentration of 55 mmHg (Ve-55) was reduced by ~24 units of volume. With CX-717 + alfentanil, it was reduced by only ~12 units of volume.

[gfp927z]

Spyderboi, You mentioned IV dosing - check out slide 10. In rats, IV dosing works TWICE as well as oral dosing in RD reversal, for the same dose level of CX-717 (30 mg/kg). A similar effect is likely for RD prevention. Dr. Stoll explained that the reason they believed they could get away with oral dosing in our studies (and he was right), was that the halflife of Ampakine in humans is approx 8 times longer than what it is in rats.

But just imagine the efficacy of the IV forms we have in the works. Not only is there an IV form of CX-717, but there's the brand new highly potent CX-1942. Stoll said this compound was specifically selected for its combination of extremely high RD activity, and excellent pro-drug/water solubility potential (slide 22). He said CX-1942 can be used in either its normal oral form, or in its water soluble IV form. CX-1942, and the IV form of CX-717, will be the compounds to forever change how RD is treated and prevented.

We can now officially add RD to ADHD as indications where Ampakines have proven themselves with statistically significant efficacy in Phase 2a human trials, and are on their way to eventual commercialization.