Assessment of 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

Study Overview
=================
Brief Summary
-----------------
This study will be conducted to evaluate the efficacy, safety, and tolerability of AVP-786 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, parallel-design study, consisting of 12 weeks of treatment. Approximately 550 participants will be enrolled at approximately 90 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, Parallel-design 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: Placebo
* Drug: AVP-786


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria Participants with clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to baseline that interferes with their daily routine and for which a prescription medication has been indicated, in the opinion of the investigator The diagnosis of agitation must meet the provisional consensus definition of agitation in participants with cognitive disorders developed by the International Psychogeriatric Association (IPA) Agitation Definition Work Group. A Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score of ≥ 4 (moderately ill) at screening and baseline Participants must have a reliable caregiver who is able and willing to comply with study procedures, including not administering any prohibited medications during the course of the study. Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend 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 AD (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, 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 |
| --- | --- |
| 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>|
| Experimental: AVP-786; Dose 1<br>Participants will receive AVP-786 (Dose 1) capsules administered twice a day over a 12-week period. | Drug: AVP-786<br>* oral capsules<br>|
| Experimental: AVP-786; Dose 2<br>Participants will receive AVP-786 (Dose 2) capsules administered twice a day over a 12-week period. | Drug: AVP-786<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 (CGIS)-Agitation Domain Score |  | 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