VistaGen Therapeutics, Inc., a biotechnology company applying stem cell technology for drug rescue, predictive toxicology and drug metabolism screening, has successfully completed its final phase 1 safety study of AV-101, a novel orally available prodrug candidate being developed for treatment of multiple conditions involving chronic neuropathic pain. The study results indicate that AV-101 is safe and well tolerated, with favorable bioavailability and pharmacokinetics.

“This important confirmation of AV-101’s safety is the final step in our phase 1 programme for AV-101,” said Shawn K Singh, JD, VistaGen’s chief executive officer. “With $8.8 million of funding from the National Institutes of Health (NIH) and outstanding strategic development and regulatory support from Cato Research Ltd., we have successfully completed the required studies enabling Phase 2 clinical development of AV-101 for multiple large market neurological diseases and conditions. In addition, recent data from the NIH suggest that the same neural pathway modified by AV-101 may be useful for treating depression. Launching a broad strategic collaboration to advance development and commercialization of AV-101 is among our key goals in 2013.”

VistaGen’s final AV-101 phase 1 safety study was a randomized, double-blind, placebo-controlled, dose-escalation clinical trial conducted at the University of California, San Diego (UCSD). The study involved three cohorts of healthy volunteers, each receiving multiple daily treatments of one of three dose levels of orally administered AV-101 over a 14-day period. The primary objectives of the study were to evaluate the safety, tolerability and pharmacokinetics (PK) of three different daily doses of AV-101 compared to placebo controls. A total of 46 healthy volunteers completed the study. The oral administration of AV-101 was safe and well tolerated by all subjects at all three dose levels tested. In addition, the PK of AV-101 was fully characterized across the range of three dose levels in the study. The data indicate that AV-101 had good bioavailability and a favorable PK profile.

“The primary safety and tolerability endpoints of the phase 1 programme were met. This is a very safe compound with no observed side effects,” commented Mark S. Wallace, MD, Chair of the Division of Pain Medicine, Department of Anesthesiology at UCSD and the principal investigator of the study. “AV-101 is an exciting prodrug compound that acts through a promising mechanism to treat pain. I am excited to move this compound into Phase 2 studies for the treatment of pain.”

Aimed at multi-billion dollar neurological disease and disorders and depression markets, AV-101, also known as “L-4-chlorokynurenine” (4-Cl-KYN), is a novel, orally available prodrug that is converted in the brain into an active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), which regulates an important neurotransmitter in the brain called the N-methyl-D-aspartate (or NMDA) receptor. A synthetic analogue of kynurenic acid, a naturally occurring neural regulatory compound, 7-Cl-KYNA is one of the most potent and selective blockers of the regulatory GlyB-site of the NMDA receptor.

VistaGen’s AV-101 IND application covers clinical development for neuropathic pain. In addition to neuropathic pain, VistaGen expects the results of its Phase 1 clinical program to be useful for supporting the development of AV-101 for other neurological disorders including depression and epilepsy.