Avanir Pharmaceuticals completed the treatment phase of a phase III clinical trial investigating the safety and effectiveness of Neurodex in treating pseudobulbar affect in patients with multiple sclerosis (MS), a company release said.

Pseudobulbar affect (PBA) is a symptom complex that is characterized by uncontrollable laughing and crying and is experienced by an estimated one million patients with neurological conditions such as ALS or Lou Gehrig's disease, Alzheimer's disease, MS, stroke and traumatic brain injury. Neurodex is the first drug product in clinical development specifically intended to treat PBA, the release says.

One hundred fifty MS patients with PBA participated in the double-blind, placebo controlled, multi-centre clinical trial. To determine suitability for inclusion in the trial, patients were assessed for PBA by clinical observation and a diagnostic tool called the Centre for Neurologic Study Lability Scale (CNS-LS).

The CNS-LS is a validated scale that measures frequency and severity of PBA episodes. The primary endpoint of the study is a comparison in the mean improvement in CNS-LS scores between patients treated with Neurodex and the placebo group. Other endpoints in the study compared the number of PBA episodes, the improvement in quality of life, the improvement in quality of relationships, and changes in pain intensity. Patients in the phase III clinical trial were treated with Neurodex or placebo on a twelve-hour dosing schedule for ninety days.

"With the completion of this trial we have achieved another major 2004 corporate objective and have moved closer to bringing Neurodex to market," said Avanir president and Chief Executive Officer Gerald J Yakatan. He added, "If, after case report clarification and statistical analyses, data from this trial confirm the results of the first phase III trial reported in 2002, they will be incorporated into a New Drug Application (NDA) seeking US marketing approval for the treatment of PBA."

The first phase III trial of Neurodex for PBA in ALS patients was completed in June 2002. This was a three-arm trial with patients randomly selected for treatment with DM alone, Q alone, or with the drug candidate Neurodex. The results of the trial for the primary endpoint and all secondary endpoints were statistically significant: adjusted mean improvement in CNS-LS for Neurodex patients compared to patients on DM alone (p=0.0013) and Q alone (p=0.0002); adjusted mean improvement in overall quality of life scores for Neurodex-treated patients compared to those on DM alone (p=0.0015) and Q alone (p=0.0013); and, adjusted mean improvement in quality of relationship scores for Neurodex patients compared to patients treated with DM alone (p less than 0.0001) and Q alone (p=0.0002).

Neurodex is a patented, orally administered combination of dextromethorphan (DM) and an enzyme inhibitor, quinidine sulfate (Q) that sustains elevated levels of DM in the human body. Results of Phase I studies have demonstrated that the combination of DM, known to be a sigma-1 agonist and NMDA receptor antagonist, and low doses of Q, resulted in higher and prolonged dextromethorphan blood levels.

Avanir has the exclusive license to develop, manufacture and market Neurodex for four potential indications: pseudobulbar affect, neuropathic pain, chronic cough and weaning drug-dependent patients from narcotics and anti-depressants.