AVP-786 is an investigational therapy being developed by Avanir Pharmaceuticals for the treatment of agitation in Alzheimer’s disease patients. It was designed as a second-generation version of Nuedexta.
How AVP-786 works
Dextromethorphan is an agent which affects signaling in the brain that triggers the cough reflex and is usually used to treat coughing. Quinidine is a medicine that affects the way the heart beats and is used to help people with certain heart rhythm disorders. It also works by increasing the amount of dextromethorphan in the body.
The addition of deuterium into the dextromethorphan molecule, in conjunction with quinidine, is thought to reduce the metabolism of dextromethorphan in the liver, prolonging its exposure in the blood.
The exact mechanism of action by which AVP-786 reduces agitation in Alzheimer’s patients is not known. However, scientists think the penetration of this molecule into the brain leads to the activation and repression of certain neuronal pathways leading to a reduction in agitation.
AVP-786 in clinical trials
The safety, tolerability, and pharmacokinetics (how the drug is processed in the body) of AVP-786 were first assessed in a Phase 1 clinical trial (NCT01787747) in healthy volunteers. Although the results of the trial were not published, Avanir announced that the medicine successfully replicated the plasma levels of Nuedexta, but with a substantially lower dose of quinidine.
Avanir conducted another Phase 1 trial (NCT02174835) to compare the safety, tolerability, and the way the drug works in the body of multiple doses of AVP-786 and Nuedexta in healthy volunteers. The study has been completed, but results have not yet been published.
The effectiveness, safety, and tolerability of AVP-786 for the treatment of agitation in patients with Alzheimer’s disease are being evaluated in two Phase 3 clinical trials called TRIAD-1 (NCT02442765) and TRIAD-2 (NCT02442778).
The primary outcome of both studies is the Cohen Mansfield Agitation Inventory (CMAI), which assesses the frequency of agitated behaviors in the patients.
TRIAD-1 aims to enroll up to 325 patients and TRIAD-2, up to 380 patients. Both trials are currently open for recruitment in more than 60 centers in the U.S.
A long-term, Phase 3 extension study (NCT02446132) of AVP-786 is currently recruiting participants from the TRIAD 1 and 2 studies, and from another trial (NCT01584440) investigating Nuedexta. During this trial, participants will receive a 52-week course of either a low or high dose of AVP-786. The trial aims to enroll up to 700 people at approximately 135 centers in North America.
In 2015, AVP-786 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of agitation in patients with Alzheimer’s disease. The designation facilitates the development and review of therapies for serious diseases with high unmet medical need.
In addition to Alzheimer’s disease, APV-786 is also being studied in schizophrenia and depression.
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