Neuropathic Pain Treatment: Phase I Trial For NGX426

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TorreyPines Therapeutics Completes Phase I Trial For NGX426, A Novel

Oral Treatment For Pain

http://www.medicalnewstoday.com/medicalnews.php?newsid=55720

TorreyPines Therapeutics, Inc. (Nasdaq: TPTX) today announced

findings from a Phase I clinical trial for NGX426, a novel oral

therapy intended for the treatment of acute migraine and chronic

pain conditions, such as neuropathic pain. The compound, an oral

prodrug of the company's lead compound, tezampanel, was found to be

well-tolerated and rapidly converted to tezampanel at all doses

tested.

This Phase I study enrolled 30 healthy adult male volunteers at one

center in the U.S. The double blind, placebo-controlled, ascending-

dose, sequential cohort study was designed to evaluate the safety,

tolerability and pharmacokinetics of NGX426, as well as to determine

the rate and extent of conversion of the prodrug, NGX426, to the

active drug tezampanel. In this study, volunteers were randomized to

receive single oral doses of 10 mg, 20 mg and 30 mg of NGX426 or

placebo. There were no dose-limiting or dose-related increases in

adverse events. Reported adverse events were generally mild in

intensity and similar to those previously reported for tezampanel.

In addition, there were no drug-related laboratory abnormalities or

clinically important changes in cardiovascular parameters.

Furthermore, pharmacokinetic analyses suggest rapid conversion of

NGX426 to tezampanel.

" With these promising results, TorreyPines is one step closer to

confirming that NGX426 is essentially an oral form of tezampanel,

our lead compound currently in Phase IIb development for acute

migraine, " said Neil Kurtz, M.D., President and Chief Executive

Officer of TorreyPines. " As an oral product candidate for pain,

NGX426 broadens and diversifies our pain pipeline and allows for

potentially multiple commercialization opportunities. "

As AMPA/kainite (AK) receptor antagonists, NGX426 and tezampanel

offer a unique mechanism of analgesia that is non-narcotic and non-

vascular in approach. As such, both compounds may effectively

relieve severe and persistent pain without imparting the risks and

side effects associated with currently available treatments.

Importantly, neither compound shows any clinically relevant effects

on the cardiovascular system in animal models or in man, nor

demonstrates interaction with serotonin receptors, so these

compounds may offer an effective alternative for migraine sufferers

for whom triptans, the current treatment standard, are

contraindicated. Tezampanel, delivered subcutaneously, is currently

in a Phase IIb clinical trial for acute migraine. NGX426 will be

studied initially for acute migraine and then for chronic pain

conditions such as neuropathic pain.

About AK Receptor Antagonists

AK receptor antagonists selectively block transmission of pain

signals mediated through the activation of a subtype of glutamate

receptors. These receptors play a critical role in the development

of central sensitization phenomena -- a key component of many pain

syndromes, including migraine and persistent pain states such as

chronic neuropathic pain. Because they do not block opioid

receptors, constrict blood vessels or interact with systems external

to the central nervous system at dosages that are therapeutically

relevant, the safety profile of AK antagonists may offer important

advantages over existing drugs.