Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

Study Overview
=================
Brief Summary
-----------------
This study will be conducted to evaluate the efficacy, safety, and tolerability of AVP-786 (deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate [Q]) compared to placebo for the treatment of agitation in participants with dementia of the Alzheimer's type.

Detailed Description
-----------------
Eligible participants for this study must have a diagnosis of probable Alzheimer's disease (AD) and must have clinically significant, moderate/severe agitation secondary to AD. This is a multicenter, randomized, double-blind, placebo-controlled study, consisting of 12 weeks of treatment. Approximately 750 participants will be enrolled at approximately 110 centers worldwide. Study medication will be administered orally twice-daily from Day 1 through Day 85. Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

Official Title
-----------------
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

Conditions
-----------------
Agitation in Patients With Dementia of the Alzheimer's Type

Intervention / Treatment
-----------------
* Drug: AVP-786
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants with a diagnosis of probable Alzheimer's disease according to the 2011 Neuropsychiatric Inventory Agitation/Aggression (NPI-AA) working groups criteria Participants with clinically significant, moderate-to-severe agitation for at least 2 weeks prior to Screening that interferes with daily routine per the Investigator's judgment Participants who require pharmacotherapy for the treatment of agitation per the Investigator's judgment after an evaluation of reversible factors and a course of nonpharmacological interventions Diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation. Participants meeting an additional predetermined blinded eligibility criterion, which will remain blinded to the clinical study site Investigators and staff Participants with a reliable caregiver who is able and willing to comply with all study procedures, including adherence to administering study drug and not administering any prohibited medications during the course of the study, and who spends a minimum of 2 hours per day for 4 days per week with the participant Exclusion Criteria: Participants with dementia predominantly of the non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia) Participants with symptoms of agitation that are not secondary to Alzheimer's dementia (e.g., secondary to pain, other psychiatric disorder, or delirium) Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy [except skin basal-cell carcinoma], poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease) Participants with myasthenia gravis

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVP-786<br>Participants will be assigned to treatment with AVP-786 capsules administered twice a day over a 12-week period. | Drug: AVP-786<br>* oral capsules<br>|
| Placebo Comparator: Placebo<br>Participants will be assigned to treatment with placebo capsules administered twice a day over a 12-week period. | Drug: Placebo<br>* oral capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score |  | Baseline; Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGI-S) Score, as Related to Agitation |  | Baseline; Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Agitation, Dementia of the Alzheimer's type, Alzheimer's disease, AVP-786, Deudextromethorphan hydrobromide, Quinidine sulfate