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

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

Treatment of disinhibition syndrome in participants with Neurodegenerative Disorder.

Study Overview

• Status: Terminated
• Conditions: Disinhibition Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: AVP-786

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo drug to be taken twice a day for 6 weeks	Drug: Placebo; matching placebo
Active Comparator: AVP-786; 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; d6-DM/Q; Other Names: Deuterated (d6)-dextromethorphan (DM)/Quinidine (Q)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Avanir Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): October 3, 2017
• Study Completion (Actual): October 3, 2017

Study Registration Dates

• First Submitted: August 11, 2015
• First Submitted That Met QC Criteria: August 25, 2015
• First Posted (Estimate): August 27, 2015

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Disinhibition
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Membrane Transport Modulators; Cytochrome P-450 Enzyme Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Antitussive Agents; Adrenergic alpha-Antagonists; Dextromethorphan; Quinidine
• Other Study ID Numbers: 15-AVP-786-203