Phase III trial of AVP 786 shows dose response in Alzheimer's agitation

Avanir Pharmaceuticals announced the results from the first study of the company's phase III clinical development program investigating the efficacy, safety and tolerability of AVP 786 (deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) for the treatment of moderate-to-severe agitation in patients with Alzheimer's dementia. This study, which used the Sequential Parallel Comparison Design (SPCD), demonstrated a significant improvement on the primary endpoint on the Cohen-Mansfield Agitation Inventory for one of the two doses being evaluated; the other dose demonstrated numerical but not significant improvement on the SPCD analysis.

Similar improvements were also observed on the key secondary endpoint. The most common adverse events in patients receiving AVP 786 versus placebo (greater than 5% incidence in either of the two doses of AVP 786) were falls, urinary tract infection, headache and diarrhea. Overall mortality during the study was low and none of the deaths were considered related to treatment.

Comment: AVP 786 is a combination of deudextromethorphan hydrobromide (d6-DM) and quinidine sulfate (Q), a CYP2D6 inhibitor. Deuteration was observed to significantly reduce susceptibility to cytochrome P450 (CYP2D6) enzyme metabolism thereby increasing the bioavailability. AVP 786 is being studied in a phase III clinical development program as a candidate for moderate-to-severe agitation in patients with Alzheimer's dementia. AVP 786 is also being investigated in patients with negative symptoms of schizophrenia and neurobehavioral disinhibition in traumatic brain injury.