ALISO VIEJO, Calif.
Sept. 4, 2012
Avanir Pharmaceuticals, Inc.
(NASDAQ: AVNR) today announced the enrollment of the first patient in study AVR-131. The study is a Phase II clinical trial investigating the use of AVP-923 for the treatment of agitation in patients with Alzheimer's disease.
"Alzheimer's disease can cause a person to exhibit marked behavioral changes that are difficult for caregivers to manage. These symptoms can include agitation, hostility, anger, and aggression, with most patients exhibiting some or all of these symptoms during the course of the disease," said
, MD, Professor of Neurotherapeutics and Drug Development in the Neurological Institute, Cleveland Clinic. "As the disease progresses, behavioral symptoms often increase in frequency and severity. With no approved therapies for agitation associated with dementia, managing these symptoms can be challenging. This trial is an important initial step in potentially providing a therapy to help manage symptoms of agitation in Alzheimer's disease."
The objectives of this proof of concept study are to evaluate the safety, tolerability, and efficacy of AVP-923 for the treatment of agitation in Alzheimer's patients. The trial is a multicenter, randomized, double-blind, placebo-controlled study that is expected to enroll up to 200 Alzheimer's patients in
the United States
. Eligible patients will be randomized to receive either AVP-923 or placebo for 10 weeks. The main efficacy measure is the Neuropsychiatric Inventory or NPI. Secondary outcome measures include assessments of disease severity, behavioral abnormalities, cognition, activities of daily living, quality of life and caregiver strain. Standard safety assessments will also be conducted.
, MD is a paid consultant of Avanir Pharmaceuticals, Inc. In addition, Dr. Cummings is the inventor of the Neuropsychiatric Inventory and receives royalties for its use.
About Behavioral Disturbances and Alzheimer's Disease
An estimated 5 million Americans have Alzheimer's disease (AD), a number that has doubled since 1980 and is expected to be as high as 16 million by 2050. AD is generally characterized by cognitive decline, impaired performance of daily activities, and behavioral disturbances. Behavioral and psychiatric symptoms develop in as many as 60% of community-dwelling dementia patients and in more than 80% of patients with dementia living in nursing homes; as the disease progresses the risk of such complications approaches 100%. Dementia-related behavioral symptoms, including agitation, can be extremely distressing to the individual, the family, and caregivers. These behavioral disturbances have been associated with more rapid cognitive decline, institutionalization, and increased caregiver burden.
AVP-923 is a combination of two well-characterized compounds: the active ingredient dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist) and low dose quinidine sulfate (a CYP2D6 enzyme inhibitor), which serves to increase the bioavailability of dextromethorphan, the ingredient active in the central nervous system, and quinidine sulfate (10 mg), a metabolic inhibitor enabling therapeutic dextromethorphan concentrations. The dosage form of AVP-923 of 20 mg DM/10 mg Q capsules (twice daily) is approved by the FDA under the brand name NUEDEXTA® which is indicated for the treatment of pseudobulbar affect (PBA). The mechanism by which NUEDEXTA exerts therapeutic effects in patients with PBA is unknown.
NUEDEXTA are not approved for the treatment of agitation in patients with Alzheimer's disease.
Important Safety Information
NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurological conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state.
Studies to support the effectiveness of NUEDEXTA were performed in patients with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NUEDEXTA has not been shown to be safe and effective in other types of emotional lability that can commonly occur, for example, in Alzheimer's disease and other dementias.