Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Alzheimer's Patients

• Safety and Tolerability [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Standard Measurements (e.g. AEs, ECG, Labs, PE and Neuro Exam)
• ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Rating) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• QoL-AD (Quality of Life - Alzheimer's Disease measure) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• CSI (Caregiver Strain Index) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

• ADCS-ADL [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• PGIC [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• ADCS-CGIC [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• QoL-AD [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• CSDD [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
• CSI [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

The objectives of the study are to evaluate the safety, tolerability and efficacy of AVP-923 compared to placebo, for the treatment of symptoms of agitation in patients with Alzheimer's Disease (AD).

Eligible patients for this study must have a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD.

This is a multicenter, randomized, double-dummy, double-blind, placebo-controlled study, consisting of 10 weeks of treatment.

Up to 200 patients will be enrolled at approximately 25 centers in the US.

Study medication will be administered orally twice-daily from Day 1 through Day 70. Screening must occur within 2 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible patients will be randomized into the study.

• Agitation
• Alzheimer's Disease

• Drug: AVP-923 (dextromethorphan/quinidine)
  AVP-923 capsules administered twice a day over a 10-week period
• Drug: Placebo
  Placebo capsules administered twice a day over a 10-week period

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: AVP-923
  Intervention: Drug: AVP-923 (dextromethorphan/quinidine)

Key Inclusion Criteria:

Diagnosis of probable Alzheimer's disease (AD).

The patient has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator.

Either out-patients or residents of an assisted-living facility or a skilled nursing home.

CGI-S score is ≥ 4 (moderately ill) at screening and baseline.

Mini Mental State Examination (MMSE) score at screening between 8 and 24(inclusive).

Caregiver who is able and willing to comply with all required study procedures, ensuring that the patient attends all study visits and takes the study medication as instructed. Caregiver must spend time with the patient a minimum of 3 times per week on 3 separate days.

Key Exclusion Criteria:

Patient has other type of dementia (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia).

Patients with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g. malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease).

Patients with myasthenia gravis.