AVANIR Pharmaceuticals announced that it has initiated a Phase II clinical trial of Neurodex for the treatment of pain in patients with diabetic neuropathy. The clinical trial is an open-label dose escalation study that will be conducted at six clinical sites in the U.S. Neurodex is a patented, orally administered combination of dextromethorphan (DM) and an enzyme inhibitor that sustains therapeutic levels of DM in the human body. The four-week open-label study will evaluate different doses of Neurodex in adult volunteers with distal symmetrical diabetic neuropathy who have daily pain in the lower extremities.

"There is ample mechanistic rationale for evaluating Neurodex in a Phase II setting for neuropathic pain," said AVANIR President and Chief Executive Officer Gerald J. Yakatan, Ph.D. "The results of our recently completed Phase II/III study with Neurodex in emotional lability provided evidence that Neurodex delivers sustained therapeutic levels of dextromethorphan. The drug may allow the neuroprotective pharmacology of dextromethorphan to be realized in chronic neuropathic pain, such as the pain experienced by people with diabetic neuropathy." Neurodex is comprised of dextromethorphan and an enzyme inhibitor that significantly slows the metabolism of DM. Although DM is considered to be neuroprotective and could be useful in treating certain central nervous system disorders based on key receptor interactions, the therapeutic utility of DM alone is limited due to its rapid metabolism. By blocking the metabolism with the inhibitor, it may be possible to maintain therapeutic levels of DM for a longer period of time with relatively small doses. AVANIR is pursuing development of Neurodex in the treatment of diabetic neuropathic pain and emotional lability.

AVANIR recently completed a Phase II/III clinical trial investigating the safety and effectiveness of Neurodex in treating emotional lability in patients with amyotrophic lateral sclerosis (ALS). The double blind, controlled, multi-center clinical trial had three treatment arms that compared Neurodex to each of its two active components, dextromethorphan and an enzyme inhibitor. The primary efficacy analysis of the study measured the change from baseline in CNS-LS scores of ALS patients with emotional lability. The CNS-LS is a validated scale that measures the severity and frequency of a subject's episodes of pathological laughing and/or crying.

Preliminary results reported in June showed the endpoint of the study was statistically significant in favor of Neurodex when compared to either of the other two treatment arms. Additional statistical analysis of the study results has confirmed efficacy in the primary endpoint as well as efficacy in pre-specified secondary endpoints. As expected based on its pharmacology, adverse events including nausea, drowsiness and dizziness were reported with greater frequency in the Neurodex group. An abstract has been submitted to the American Neurological Association conference scheduled for October 2002. If accepted, detailed data on the clinical trials will be presented at that meeting.