Safety, Tolerability and Efficacy of AVP-786 for the Treatment of Disinhibition

Study Overview
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Brief Summary
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Treatment of disinhibition syndrome in participants with Neurodegenerative Disorder.

Detailed Description
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Eligible participants for this study must have a diagnosis of Neurodegenerative Disorder and must exhibit disinhibition syndrome of sufficient severity to warrant treatment. This is a multicenter, randomized, double-blind, placebo-controlled, cross-over study consisting of two 6-week treatment periods. Approximately 12 participants will be enrolled at approximately 2 centers in the United States. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Efficacy of AVP-786 for the Treatment of Disinhibition in Patients With Neurodegenerative Disorders

Conditions
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Disinhibition Syndrome

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of a Neurodegenerative Disorder including frontotemporal dementia, Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with Lewy bodies (DBL), vascular cognitive disorders, or Huntington's disease, at least 3 months prior to Baseline The participant has behavior from 2 of the 3 categories of disinhibited behavior from the definition of the behavioral variant of frontotemporal dementia The behavioral changes are not due to a pre-existing major psychiatric disorder (e.g., schizophrenia, bipolar disease, etc.) and are not due to the direct effect of systemic illness, drug action, or substance use Disinhibition scale score of ≥4 on the 3 core disinhibition items of the Frontal Behavioral Inventory (FBI) at Screening and Baseline Exclusion Criteria: Participants with symptoms of disinhibition that is not secondary to Neurodegenerative Disorders Participants with myasthenia gravis 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 or untreated prostate cancer], poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)

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: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo drug to be taken twice a day for 6 weeks | Drug: Placebo<br>* matching placebo<br>|
| Active Comparator: AVP-786<br>Participants randomized to AVP-786 will take one dose of AVP-786 once a day and one dose of placebo once a day for the first 7 days; from day 8, participants will receive AVP-786 twice a day for 5 weeks. | Drug: AVP-786<br>* d6-DM/Q<br>* Other names: Deuterated (d6)-dextromethorphan (DM)/Quinidine (Q);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Disinhibition Domain of the Neuropsychiatric Inventory (NPI) |  | Baseline; Week 6, Week 8, and Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline for the Total NPI Score |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the NPI Total Caregiver Distress |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the NPI Disinhibition Domain Caregiver Distress |  | Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14 | 
| Change From Baseline for the Frontal Behavioral Inventory (FBI) Total Score |  | Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14 | 
| Change From Baseline for the FBI Disinhibition Domain Score |  | Baseline; Week 1, Week 3, Week 6, Week 9, Week 11, and Week 14 | 
| Change From the First Assessment for the Modified Clinical Global Impression of Change (mCGIC) Scale |  | Week 3, Week 6, Week 11, and Week 14 | 
| Change From the First Assessment for the Patient Global Impression of Change (PGIC) Scale |  | Week 3, Week 6, Week 11, and Week 14 | 
| Change From Baseline for the Quality of Relationships (QoR) Scale |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the Quality of Life (QoL) Scale |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the Interpersonal Reactivity Index (IRI) |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the Center for Neurologic Study-Lability Scale (CNS-LS) |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the Mini-Mental State Examination (MMSE) |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the Cornell Scale for Depression in Dementia (CSDD) |  | Baseline; Week 6, Week 8, and Week 14 | 
| Change From Baseline for the Stroop Color and Word Task |  | Baseline; Week 6, Week 8, and Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Disinhibition