AVP-786: Phase I data

Data from 36 healthy volunteers in the first stage of a double-blind, crossover Phase I trial showed that AVP-786 plus low-dose quinidine had a comparable pharmacokinetic, safety and tolerability profile to that of AVP-923, a combination product containing dextromethorphan and a higher dose of quinidine (10 mg) than that given with AVP-786. Avanir said AVP-786 and AVP-923 contained the same amount of dextromethorphan in the trial, but declined to disclose the actual dose. The second stage of the trial, which has enrolled 12 additional subjects, will evaluate even lower doses of quinidine given with AVP-786. Avanir said it hopes that lower doses of the drug will reduce the cardiovascular risk and drug-drug interactions associated with quinidine. The company markets a 20/10 mg formulation of dextromethorphan/quinidine in the U.S. as Nuedexta to treat pseudobulbar affect (PBA), which is characterized by involuntary episodes of laughing and/or crying. Nuedexta is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome or a history suggestive of Torsades de Pointes, and in patients with heart failure.

The successful completion of the first stage of the Phase I trial triggered an undisclosed milestone payment to Concert under a 2012 deal granting Avanir exclusive, worldwide rights to develop and commercialize Concert's deuterium-modified dextromethorphan compounds, including AVP-786 (see BioCentury, March 5, 2012). Dextromethorphan is a generic NMDA receptor antagonist while quinidine is a cytochrome P450 2D6 enzyme inhibitor. ...