Avanir Pharmaceuticals has begun enrollment in a multicenter, randomized, double-blind, placebo-controlled Phase II study of AVP-786 for the treatment of neurobehavioral disinhibition, including aggression, agitation and irritability in patients with traumatic brain injury (TBI). Approximately 150 patients with non-penetrating TBI will be treated for up to 12 weeks at approximately 25 centers in the U.S. to evaluate the efficacy, safety and tolerability of AVP-786.
"Dysfunctional behaviors – such as aggression, agitation and irritability – are estimated to occur in more than half of adults with TBI. These behaviors are amongst the most debilitating consequence of TBI and dramatically impact family, inter-personal and work relationships," Richard Malamut, MD, chief medical officer, Avanir said. "Initiating this Phase II study is an important milestone in evaluating AVP-786 as a treatment to help alleviate these disruptive symptoms."
AVP-786 is a novel, next-generation investigational drug product consisting of a combination of deudextromethorphan (an uncompetitive NMDA receptor antagonist, sigma-1 receptor agonist and inhibitor of the serotonin (SERT) and norepinephrine (NET) transporters), and an ultra-low dose of quinidine. Incorporation of deuterium into the dextromethorphan molecule has been shown to reduce first-pass liver metabolism. By having a lower rate of metabolism, deudextromethorphan requires an ultra-low dose of quinidine (an inhibitor of the enzyme CYP 2D6) in the AVP-786 formulation. This may result in a reduced potential for drug interactions and cardiac effects. AVP-786 is an investigational drug not approved by the FDA.