Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

Study Overview
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Brief Summary
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This is an extension study of the Phase 3 Studies 15-AVP-786-301, 15-AVP-786-302, and 17-AVP-786-305, which also allows participants from the Phase 2 Study 12-AVR-131 to be included.

Detailed Description
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Participant has successfully completed Studies 15-AVP-786-301, 15-AVP-786-302, 12-AVR-131, or 17-AVP-786-305. Participants will be enrolled in the study for approximately 56 weeks (participants who have a follow-up visit 3 months after the last dose of treatment will be enrolled for approximately 64 weeks). Approximately 1200 participants will be enrolled at approximately 250 centers globally. All participants enrolled will receive AVP-786; the treatment dose assigned will be masked to the participant, investigator, study staff, and the sponsor.

Official Title
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A Phase 3, Multicenter, Long Term, Extension Study of the Safety and Efficacy of AVP-786 (Deuterated [d6] Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

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

Intervention / Treatment
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* Drug: AVP-786


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has successfully completed Studies 15-AVP-786-301, 15-AVP-786-302, 12-AVR-131, or 17-AVP-786-305. (Note: A delay in enrollment may include delays associated with COVID-19 restrictions.) Participants with a diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working group criteria Either out-patients or residents of an assisted-living facility or a skilled nursing home Participants who delay enrollment must have clinically significant, moderate/severe agitation at least 2 weeks prior to baseline Participants who delay enrollment must have a diagnosis of agitation that must meet the International Psychogeriatric Association (IPA) provisional definition of agitation Participants who delay enrollment must have a Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation of ≥ 4 (moderately ill) at screening and baseline Participants who delay enrollment must have a Mini-Mental State Examination (MMSE) score between 6 and 26 (inclusive) at screening and baseline Exclusion Criteria: 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 determined to have a high imminent risk of falls during the study based on a clinical evaluation by the investigator Participants who are currently using or were on NUEDEXTA® in the 2 weeks preceding baseline

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVP-786 (dose 1)<br>AVP-786 dose 1; capsules administered twice a day over a 52-week period | Drug: AVP-786<br> <br> |
| Experimental: AVP-786 (dose 2)<br>AVP-786 dose 2; capsules administered twice a day over a 52-week period | Drug: AVP-786<br> <br> |
| Experimental: AVP-786 (dose 3)<br>AVP-786 dose 3; capsules administered twice a day over a 52-week period | Drug: AVP-786<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with any Treatment-Emergent Adverse Event |  | up to 64 weeks | 
| Number of Participants with any Treatment-Emergent Serious Adverse Event |  | up to 64 weeks | 
| Number of Participants with any abnormal, clinically significant Clinical Laboratory Value |  | up to 52 weeks | 
| Number of Participants with any abnormal, clinically significant 12-lead Electrocardiogram (ECG) value |  | up to 52 weeks | 
| Number of Participants with any abnormal, clinically significant Physical and Neurological Examination finding |  | up to 52 weeks | 
| Number of participants with any abnormal, clinically significant vital sign value |  | up to 52 weeks | 
| Change from Baseline to Week 64 in the Sheehan Suicidality Tracking Scale (S-STS) Score |  | Baseline; Week 64 | 
| Change from Baseline to Week 52 in the Mini-Mental State Examination (MMSE) Score |  | Baseline; Week 52 | 
| Change from Baseline to Week 52 in the Epworth Sleepiness Scale (ESS) Score |  | Baseline; Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 64 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score |  | Baseline; Week 64 | 
| Change from Baseline to Week 52 in the Agitation/Aggression, Irritability/Lability, and Aberrant Motor Behavior Domain Scores of the Neuropsychiatric Inventory (NPI) |  | Baseline; Week 52 | 
| Change from Baseline to Week 64 in the modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change-Agitation (mADCS-CGIC-Agitation) Score |  | Baseline; Week 64 | 
| Change from Baseline to Week 52 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score |  | Baseline; Week 52 | 
| Change from Baseline to Week 52 in the Patient Global Impression of Change (PGIC) Score | PGIC (rated by caregiver) | Baseline; Week 52 | 
| Change from Baseline to Week 52 in the Dementia Quality of Life (DEMQOL) Score |  | Baseline; Week 52 | 
| Change from Baseline to Week 52 in the Resource Utilization in Dementia (RUD) Score |  | Baseline; Week 52 | 
| Change from Baseline to Week 52 in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) for Participants from Study 17-AVP-786-305 |  | Baseline; Week 52 |