This excerpt taken from the TPTX 8-K filed Dec 1, 2008.
Endpoints in Reducing Capsaicin-Induced Pain in Healthy Subjects
LA JOLLA, CA, December 1, 2008 TorreyPines Therapeutics, Inc. (Nasdaq: TPTX) today announced that oral administration of NGX426, an AMPA/kainate-type glutamate receptor antagonist, demonstrated a statistically significant reduction in spontaneous pain, hyperalgesia (abnormally increased pain state) and allodynia (pain resulting from normally non-painful stimuli to the skin) compared to placebo following intradermal injections of capsaicin in a human experimental model of cutaneous pain, hyperalgesia and allodynia.
Human experimental models of pain are emerging as tools to predict efficacy of novel analgesics in early clinical trials, said principal investigator Mark Wallace, M.D., Professor of Clinical Anesthesiology and Program Director, University of California San Diego Center for Pain Medicine. The results of NGX426 in this study are exciting and suggest that this drug will be effective in clinical pain states. These study results should provide guidance in the development of Phase II clinical trials.
The single-center, in-clinic, randomized, double-blinded study enrolled a total of 18 healthy male subjects. Using a three-period cross-over design, subjects received two intradermal injections of capsaicin at 30 minutes and 120 minutes after administration of a single, oral dose of 90 mg or 150 mg of NGX426, or placebo. Pain assessments were determined at specified intervals after each injection of capsaicin and measured by visual analog scale.
The 90 mg and 150 mg doses of NGX426 demonstrated analgesic effect on the primary endpoints. The 150 mg dose was statistically significant compared to placebo on all three measures: reduction in spontaneous pain, hyperalgesia and allodynia. The 90 mg dose also showed statistical significance on reduction of hyperalgesia and allodynia and trended toward statistical significance on reduction in spontaneous pain. In addition, a statistically significant pain-reducing effect was observed for the 150 mg dose through 4.5 hours post-dosing.
NGX426 was well tolerated and all subjects completed the three treatment periods. There were no serious or medically important adverse events or changes on laboratory or ECG parameters. The most common adverse events associated with NGX426 administration were mild somnolence and dizziness.
We are very encouraged by these results that show an analgesic effect for NGX426 in this well-accepted pain model, said Ev Graham, Chief Executive Officer of TorreyPines. As an oral, non-opioid pain agent, NGX426 could address the significant and documented unmet needs in treating a range of chronic pain conditions including neuropathic pain and acute or prophylactic treatment of migraine. These data, as well as data from our on-going Phase I multiple dose trial, will help us structure our Phase II development plan for NGX426.
NGX426, an ester prodrug, is an oral form of tezampanel, TorreyPines most advanced product candidate. Pharmacokinetic analyses from two Phase I studies confirmed that when given to humans, NGX426 is rapidly converted to tezampanel, the active moiety. Six Phase II, double-blind, placebo-controlled trials have demonstrated that tezampanel, administered either subcutaneously or intravenously, was more effective than placebo in relieving pain across migraine, nociceptive and neuropathic pain models, including a capsaicin-induced pain model.
In order to pursue the Phase II clinical development of NGX426 TorreyPines intends to explore both strategic and financing initiatives.