AVP-786 for the treatment of agitation in dementia of the Alzheimer's type.

ABSTRACT

INTRODUCTION: Agitation is common and distressing in patients with Alzheimer-type dementia, but safe, effective treatments remain elusive. Psychological treatments are first-line options, but they have limited efficacy. Off-label psychotropic medications are frequently used, but they also have limited effectiveness, and their use may have harmful side effects, including death. Areas covered This review discusses the history leading to the conception of AVP-786 (deuterated (d6)-dextromethorphan/quinidine), its pharmacokinetic and pharmacodynamic profiles and safety issues, together with an overview of recent clinical trials. Data were found in the medical literature, in US and EU clinical trial registries and in information provided by the manufacturer. Expert opinion AVP-786 is one of six investigational compounds in recent phase III clinical development for agitation in Alzheimer disease (AD). Quinidine and deuteration appear to prolong dextromethorphan's plasma half-life and facilitate brain penetration. The FDA granted fast-track designation to AVP-786 and allowed use of data generated on dextromethorphan-quinidine (AVP-923, Nuedexta®) for regulatory filings. AVP-923 reduced agitation in AD and was well tolerated in a phase II RCT that included more than 200 patients. A phase III clinical development program of AVP-786 for AD agitation was recently initiated. This program is expected to start generating results in July 2018.