Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Neurobehavioral Disinhibition Including Aggression, Agitation, and Irritability in Participants With Traumatic Brain Injury

NCT ID: NCT03095066

Last Updated: 2025-10-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

168 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-30

Study Completion Date

2022-08-31

Brief Summary

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This is a multicenter, randomized, placebo-controlled study to evaluate AVP-786 for the treatment of neurobehavioral disinhibition including aggression, agitation, and irritability in participants with traumatic brain injury (TBI).

Detailed Description

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Eligible participants for this study must have a diagnosis of neurobehavioral disinhibition including aggression, agitation, and irritability that persists after brain injury.

This is a multicenter, randomized, placebo-controlled study, consisting of up to 12 weeks of treatment.

Conditions

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Neurobehavioral Disinhibition

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Stage 1: Placebo Non-responders to Stage 2: Placebo

Participants who were randomized to receive placebo in Stage 1 and were classified as non-responders (responders" if modified Clinical Global Impression of Severity \[mCGI-S\] score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered as capsules

Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786

Participants received AVP-786 matching placebo capsules, orally, twice daily (BID) during Weeks 1 to 6 of the Stage 1 treatment period. After Week 6 participants were classified as responders or non-responders and were re-randomized to receive either placebo, orally, BID or AVP-786 in a dose escalation schedule to reach the target dose of AVP-786-42.63/4.9, orally, BID during Week 7 to Week 12 of Stage 1 treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered as capsules

AVP-786-42.63

Intervention Type DRUG

42.63 mg of d6-DM and 4.9 mg of Q

Overall Study: Stage 1 AVP-786/Stage 2 AVP-786

Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 12 of the treatment period.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Administered as capsules

AVP-786-28

Intervention Type DRUG

28 mg of d6-DM and 4.9 mg of Q

AVP-786-42.63

Intervention Type DRUG

42.63 mg of d6-DM and 4.9 mg of Q

Stage 1: Placebo

Participants received AVP-786 matching placebo capsules, orally, BID during Weeks 1 to 6 of the Stage 1 treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered as capsules

Stage 1: Placebo Non-responders to Stage 2: AVP-786

Participants who received placebo in Stage 1 and were classified as non-responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline. Participants who did not meet these criteria were considered "non-responders) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28- 28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28 -28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID during Weeks 9 to 12 of the Stage 2 treatment period.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Administered as capsules

AVP-786-28

Intervention Type DRUG

28 mg of d6-DM and 4.9 mg of Q

AVP-786-42.63

Intervention Type DRUG

42.63 mg of d6-DM and 4.9 mg of Q

Stage 1: Placebo Responders to Stage 2: Placebo

Participants who were randomized to receive placebo in Stage 1 and were classified as responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline) after Week 6 were re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered as capsules

Stage 1: Placebo Responders to Stage 2: AVP-786

Participants who received placebo in Stage 1 and were classified as responders (responders" if mCGI-S score is ≤ 3 at Day 43 and NPI-C-3 score has decreased by ≥ 25% from baseline) after Week 6 were re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28- 28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28 -28/4.9 capsule, orally, BID during Week 8, and AVP-786-42.63/4.9 capsules, orally, BID during Weeks 9 to 12 of the Stage 2 treatment period.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Administered as capsules

AVP-786-28

Intervention Type DRUG

28 mg of d6-DM and 4.9 mg of Q

AVP-786-42.63

Intervention Type DRUG

42.63 mg of d6-DM and 4.9 mg of Q

Stage 1: AVP-786

Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) during Week 1 followed by AVP-786-28/4.9 capsule, orally, BID during Week 2, and AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules (target dose), orally, BID during Weeks 3 to 6 of the Stage 1 treatment period.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Administered as capsules

AVP-786-28

Intervention Type DRUG

28 mg of d6-DM and 4.9 mg of Q

AVP-786-42.63

Intervention Type DRUG

42.63 mg of d6-DM and 4.9 mg of Q

Interventions

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Placebo

Administered as capsules

Intervention Type DRUG

AVP-786-28

28 mg of d6-DM and 4.9 mg of Q

Intervention Type DRUG

AVP-786-42.63

42.63 mg of d6-DM and 4.9 mg of Q

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participants with TBI
* Participants with neurobehavioral disinhibition symptoms that are present after trauma or after recovery of consciousness
* Score of ≥4 on the mCGI-S scale and the Agitation/Aggression or Irritability/Lability subscales of the Neuropsychiatric Inventory (NPI) scale at screening and baseline
* Participants with a reliable caregiver

Exclusion Criteria

* Participants with significant symptoms of a major depressive disorder
* Participants with a history of or current clinical symptoms of schizophrenia, schizoaffective disorder, bipolar disorder, antisocial personality disorder, or borderline personality disorder
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Tuscaloosa Veterans Affairs Medical Center

Tuscaloosa, Alabama, United States

Site Status

Absolute Clinical Research Site#207

Phoenix, Arizona, United States

Site Status

Perseverance Research Center Site#152

Scottsdale, Arizona, United States

Site Status

ATP Clinical Research Site#150

Costa Mesa, California, United States

Site Status

Kaizen Brain Center #224

La Jolla, California, United States

Site Status

Sunwise Clinical Research, LLC Site#216

Lafayette, California, United States

Site Status

Torrance Clinical Research Institute Site#157

Lomita, California, United States

Site Status

Tibor Rubin VA Medical Center, SCIRE Biomedical Research Institute

Long Beach, California, United States

Site Status

Asclepes Research Centers - Panorama City Site #208

Panorama City, California, United States

Site Status

The Neurology Group

Pomona, California, United States

Site Status

Mountain Mind

Colorado Springs, Colorado, United States

Site Status

Mountain View Clinical Research, Inc. Site# 202

Denver, Colorado, United States

Site Status

Medical Center of the Rockies

Loveland, Colorado, United States

Site Status

Connecticut Clinical Research

Cromwell, Connecticut, United States

Site Status

Bradenton Research Center, Inc

Bradenton, Florida, United States

Site Status

Healthcare Innovative Institute, LLC Site# 173

Coral Springs, Florida, United States

Site Status

Science Connections, LLC Site#161

Doral, Florida, United States

Site Status

Design Neuroscience Center, PL

Doral, Florida, United States

Site Status

Alphab Global Research Site#163

Jupiter, Florida, United States

Site Status

Meridien Research

Maitland, Florida, United States

Site Status

Premier Clinical Research Institute, Inc.

Miami, Florida, United States

Site Status

Project 4 Research

Miami, Florida, United States

Site Status

Allied Biomedical Research Institute, Inc. Site#151

Miami, Florida, United States

Site Status

Health Synergy Clinical Research

Okeechobee, Florida, United States

Site Status

Roskamp Institute Clinic, Inc.

Sarasota, Florida, United States

Site Status

USF Dept of Psychiatry and Behavioral Neurosciences Site# 214

Tampa, Florida, United States

Site Status

Meridien Research Site# 108

Tampa, Florida, United States

Site Status

Hawaii Pacific Neuroscience Site#184

Honolulu, Hawaii, United States

Site Status

The University of Kentucky research foundation

Lexington, Kentucky, United States

Site Status

Baptist Health

Richmond, Kentucky, United States

Site Status

Sisu BHR Site#200

Springfield, Massachusetts, United States

Site Status

Neurobehavioral Medicine Group #222

Bloomfield Hills, Michigan, United States

Site Status

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, United States

Site Status

Sharlin Health and Neurology

Ozark, Missouri, United States

Site Status

Clinical Research Professionals

St Louis, Missouri, United States

Site Status

JFK Johnson Rehabilitation Institute

Edison, New Jersey, United States

Site Status

The NeuroCognitive Insititute

Mount Arlington, New Jersey, United States

Site Status

New York University School of Medicine Site #122

New York, New York, United States

Site Status

Atrium Health - Carolinas Rehabilitation - Charlotte Site #166

Charlotte, North Carolina, United States

Site Status

New Hope Clinical Research Site#194

Charlotte, North Carolina, United States

Site Status

Carolina Headache Institute

Durham, North Carolina, United States

Site Status

Salisbury VAMC

Salisbury, North Carolina, United States

Site Status

Valley Medical Research

Centerville, Ohio, United States

Site Status

Cincinnati VA Medical Center

Cincinnati, Ohio, United States

Site Status

North Star Medical Research, LLC Site#154

Middleburg Heights, Ohio, United States

Site Status

IPS Research Site#196

Oklahoma City, Oklahoma, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

WJB Dorn VA-Wm. Jennings Bryan Dorn VA Medical Center

Columbia, South Carolina, United States

Site Status

University of Texas Southwestern Medical Site#140

Dallas, Texas, United States

Site Status

Polytrauma Rehabilitation Center S. Texas VA Health Care System Site# 146

San Antonio, Texas, United States

Site Status

Cedar Clinical Research #221

Draper, Utah, United States

Site Status

Virginia Commonwealth University #172

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University Site#172

Richmond, Virginia, United States

Site Status

Salem Research Institute Site# 138

Salem, Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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17-AVP-786-205

Identifier Type: -

Identifier Source: org_study_id

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