Neurobehavioral DisinhibitionPhase 2NCT03095066
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
A Phase 2 study testing AVP-786-28 and AVP-786-42.63 in people with Neurobehavioral Disinhibition, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 54 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neurobehavioral Disinhibition
- What is being tested?
- AVP-786-28 and AVP-786-42.63
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- 54 sitesUnited States
- Study dates
- 30 May 2017to 31 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
54 sites in 1 country.
54 sites in 1 country
United States54 sites
Neurobehavioral Medicine Group #222
Bloomfield Hills, Michigan, 48302
Bradenton Research Center, Inc
Bradenton, Florida, 34205
Valley Medical Research
Centerville, Ohio, 45459
Atrium Health - Carolinas Rehabilitation - Charlotte Site #166
Charlotte, North Carolina, 28203
New Hope Clinical Research Site#194
Charlotte, North Carolina, 28211
Cincinnati VA Medical Center
Cincinnati, Ohio, 45220
Mountain Mind
Colorado Springs, Colorado, 80903
WJB Dorn VA-Wm. Jennings Bryan Dorn VA Medical Center
Columbia, South Carolina, 29205
Healthcare Innovative Institute, LLC Site# 173
Coral Springs, Florida, 33067
ATP Clinical Research Site#150
Costa Mesa, California, 92626
Millennium Psychiatric Associates, LLC
Creve Coeur, Missouri, 63141
Connecticut Clinical Research
Cromwell, Connecticut, 06416
University of Texas Southwestern Medical Site#140
Dallas, Texas, 75390
Mountain View Clinical Research, Inc. Site# 202
Denver, Colorado, 80209
Science Connections, LLC Site#161
Doral, Florida, 33166
Design Neuroscience Center, PL
Doral, Florida, 33172
Cedar Clinical Research #221
Draper, Utah, 84020
Carolina Headache Institute
Durham, North Carolina, 27713
JFK Johnson Rehabilitation Institute
Edison, New Jersey, 08820
Hawaii Pacific Neuroscience Site#184
Honolulu, Hawaii, 96817
Alphab Global Research Site#163
Jupiter, Florida, 33458
Kaizen Brain Center #224
La Jolla, California, 92037
Sunwise Clinical Research, LLC Site#216
Lafayette, California, 94543
The University of Kentucky research foundation
Lexington, Kentucky, 40536
Torrance Clinical Research Institute Site#157
Lomita, California, 90717
Tibor Rubin VA Medical Center, SCIRE Biomedical Research Institute
Long Beach, California, 90822
Medical Center of the Rockies
Loveland, Colorado, 80538
Meridien Research
Maitland, Florida, 32751
Premier Clinical Research Institute, Inc.
Miami, Florida, 33122
Project 4 Research
Miami, Florida, 33125
Allied Biomedical Research Institute, Inc. Site#151
Miami, Florida, 33155
North Star Medical Research, LLC Site#154
Middleburg Heights, Ohio, 44130
The NeuroCognitive Insititute
Mount Arlington, New Jersey, 07856
New York University School of Medicine Site #122
New York, New York, 10016
Health Synergy Clinical Research
Okeechobee, Florida, 34972
IPS Research Site#196
Oklahoma City, Oklahoma, 73106
Sharlin Health and Neurology
Ozark, Missouri, 65721
Asclepes Research Centers - Panorama City Site #208
Panorama City, California, 91402
Absolute Clinical Research Site#207
Phoenix, Arizona, 85051
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
The Neurology Group
Pomona, California, 91767
Baptist Health
Richmond, Kentucky, 40475
Virginia Commonwealth University #172
Richmond, Virginia, 23298
Virginia Commonwealth University Site#172
Richmond, Virginia, 23298
Salem Research Institute Site# 138
Salem, Virginia, 24153
Salisbury VAMC
Salisbury, North Carolina, 28144
Polytrauma Rehabilitation Center S. Texas VA Health Care System Site# 146
San Antonio, Texas, 78229
Roskamp Institute Clinic, Inc.
Sarasota, Florida, 34243
Perseverance Research Center Site#152
Scottsdale, Arizona, 85254
Sisu BHR Site#200
Springfield, Massachusetts, 01103
Clinical Research Professionals
St Louis, Missouri, 63141
USF Dept of Psychiatry and Behavioral Neurosciences Site# 214
Tampa, Florida, 33613
Meridien Research Site# 108
Tampa, Florida, 33634
Tuscaloosa Veterans Affairs Medical Center
Tuscaloosa, Alabama, 35404
About this study
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Neurobehavioral Disinhibition Including Aggression, Agitation, and Irritability in Patients With Traumatic Brain Injury (TBI).
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).
Read the detailed description
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
- Neurobehavioral Disinhibition
- Being tested
- Placebo, AVP-786-28, AVP-786-42.63
- Keywords
- aggression, agitation, irritability, non-penetrating brain injury, traumatic brain injury, TBI, AVP-786
- Medical subject headings
- Aggression, Psychomotor Agitation, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Administered as capsules
AVP-786-28Drug
28 mg of d6-DM and 4.9 mg of Q
AVP-786-42.63Drug
42.63 mg of d6-DM and 4.9 mg of Q
| Study group | Role | What they receive |
|---|---|---|
| Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786 | Placebo comparator | 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. Receives: Drug: Placebo; Drug: AVP-786-42.63 |
| Overall Study: Stage 1 AVP-786/Stage 2 AVP-786 | Experimental | 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. Receives: Drug: Placebo; Drug: AVP-786-28; Drug: AVP-786-42.63 |
| Stage 1: Placebo | Placebo comparator | Participants received AVP-786 matching placebo capsules, orally, BID during Weeks 1 to 6 of the Stage 1 treatment period. Receives: Drug: Placebo |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Experimental | 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. Receives: Drug: Placebo; Drug: AVP-786-28; Drug: AVP-786-42.63 |
| Stage 1: Placebo Responders to Stage 2: Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Stage 1: Placebo Responders to Stage 2: AVP-786 | Experimental | 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. Receives: Drug: Placebo; Drug: AVP-786-28; Drug: AVP-786-42.63 |
| Stage 1: AVP-786 | Experimental | 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. Receives: Drug: Placebo; Drug: AVP-786-28; Drug: AVP-786-42.63 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscale of Aggression, Agitation, and Irritability/Lability (NPI-C-3)
NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These are collectively rated first by the informant/caregiver based on frequency (0-4);severity (0-3);informant/caregiver distress (0-5) \& then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C-3= aggression, agitation, \& irritability/lability subscales. NPI-C agitation domain= sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain= sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain= sum of clinician impression severity scores for irritability/lability questions 1-12 (score=0-36). NPI-C-3 composite score ranges from 0-99. Higher score= increased severity. Least square (LS) mean was analyzed using mixed effects model repeated measures (MMRM) analysis.
Measured: Baseline to Week 6
Stage 2: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the NPI-C Subscale of NPI-C-3
NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These domains are collectively rated by the informant/caregiver based on frequency (0-4), severity (0-3) \& informant/caregiver distress (0-5), then by participant based on frequency (0-4), which is integrated by clinician into (0-3) clinical impression severity rating. NPI-C-3=aggression, agitation, \& irritability/lability subscales. NPI-C agitation domain=sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain=sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain=sum of clinician impression severity scores for irritability/lability questions 1-12 (score= 0-36). NPI-C-3 composite score ranges from 0-99. Higher score=increased severity. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis.
Measured: Week 7 to Week 12
Secondary outcomes (8)
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Aggression
The NPI-C was used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) \& informant/caregiver distress (0-5), then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C aggression domain score is the sum of clinician impression severity scores for aggression questions 1-8, score ranges from 0-24, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed= number of participants with data available for analysis. Number analyzed= number of participants with data available for analysis at the specified time point.
Measured: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Agitation
The NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) \& informant/caregiver distress (0-5), then by the participant based on frequency (0 to 4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C agitation domain score is the sum of clinician impression severity scores for agitation questions 1-13, score ranges from 0-39, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point.
Measured: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Irritability/Lability
NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) \& informant/caregiver distress (0-5), then by the participant based on frequency (0 to 4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C irritability/lability domain score=sum of clinician impression severity scores for irritability/lability questions 1-12, score ranges from 0-36, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point.
Measured: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Disinhibition
The NPI-C is used to rate the presence of neuropsychiatric symptoms across 12 domains. The 12 domains are collectively rated first by the informant/caregiver based on frequency (0-4), severity (0-3) \& informant/caregiver distress (0-5), then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. The NPI-C disinhibition domain score is the sum of clinical impression severity scores for disinhibition questions 1-16, score ranges from 0-48, where higher score indicates greater clinical severity of symptom. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis. Number analyzed=number of participants with data available for analysis at the specified time point.
Measured: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in Modified Clinical Global Impression of Severity (mCGI-S) Scale Scores
mCGI-S is 7-point (1-7) scale requiring clinician to rate severity of participant's neurobehavioral disinhibition including aggression, agitation and irritability after NPI-C interview, at time of assessment relative to clinician's past experience with participants having same diagnosis. Considering total clinical experience, participant is assessed on severity of illness at time of rating as:0: not assessed;1: normal, not at all ill;2: borderline ill;3: mildly ill;4: moderately ill;5: markedly ill;6: severely ill;7: among most extremely ill participants. Higher score=increased severity. Negative change from baseline=improvement.LS mean was analyzed using analysis of covariance (ANCOVA) model. Overall number analyzed=participants with data available for analysis. Number analyzed=participants with data available for analysis at specified time point.
Measured: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores
The PGI-S is a single-question scale used to assess the severity of symptoms of neurobehavioral disinhibition including aggression, agitation, and irritability, on a 7-point scale, as 1: normal, not at all ill; 2: borderline ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; or 7: extremely ill. A higher score indicates worsening of the symptoms. Negative change from baseline indicates improvement. LS mean was analyzed using ANCOVA model. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
Measured: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Modified Clinical Global Impression of Change (mCGI-C) Raw Scores
The mGCI-C is a scale that requires the clinician to rate the change of the participant's neurobehavioral disinhibition including aggression, agitation, and irritability at the time of assessment after the NPI-C interview, relative to the clinician's past experience with the participant's neurobehavioral disinhibition at admission. Considering total clinical experience, a participant is assessed for change of mental illness as: 0: not assessed; 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; 7: very much worse. A higher score represents worsening of symptoms. Negative change from baseline indicates improvement.
Measured: Stage 1: Week 6; Stage 2: Week 12
Stage 1 and Stage 2: Patient Global Impression of Change (PGI-C) Raw Scores
The PGI-C is a 7-point (1-7) scale used to assess treatment response, and it is rated as: 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; 7: very much worse. A higher score indicates worsening of the symptoms. Negative change from baseline indicates improvement. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
Measured: Stage 1: Week 6; Stage 2: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2017
- Study start30 May 2017
- Primary completion22 Aug 2022
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neurobehavioral DisinhibitionStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03095066
- Sponsor's protocol ID
- 17-AVP-786-205
- Status last verified
- Oct 2025
- First submitted
- 23 Mar 2017
- Last updated
- 29 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Neurobehavioral Disinhibition Including Aggression, Agitation, and Irritability in Patients With Traumatic Brain Injury (TBI).
- ClinicalTrials.gov ID
- NCT03095066
- Acronym / sponsor ID
- 17-AVP-786-205
- Conditions
- Neurobehavioral Disinhibition
- Keywords
- aggression, agitation, irritability, non-penetrating brain injury, traumatic brain injury, TBI, AVP-786
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 May 2017 (actual)
- Primary completion
- 22 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 29 Mar 2017 (actual)
- Results
- Posted 29 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786 | Placebo comparator | Drug: Placebo, Drug: AVP-786-42.63Participants 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. |
| Overall Study: Stage 1 AVP-786/Stage 2 AVP-786 | Experimental | Drug: Placebo, Drug: AVP-786-28, Drug: AVP-786-42.63Participants 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. |
| Stage 1: Placebo | Placebo comparator | Drug: PlaceboParticipants received AVP-786 matching placebo capsules, orally, BID during Weeks 1 to 6 of the Stage 1 treatment period. |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786 | Experimental | Drug: Placebo, Drug: AVP-786-28, Drug: AVP-786-42.63Participants 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. |
| Stage 1: Placebo Responders to Stage 2: Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
| Stage 1: Placebo Responders to Stage 2: AVP-786 | Experimental | Drug: Placebo, Drug: AVP-786-28, Drug: AVP-786-42.63Participants 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. |
| Stage 1: AVP-786 | Experimental | Drug: Placebo, Drug: AVP-786-28, Drug: AVP-786-42.63Participants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAdministered as capsules | Drug | Overall Study: Stage 1 AVP-786/Stage 2 AVP-786, Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786, Stage 1: AVP-786, Stage 1: Placebo, Stage 1: Placebo Non-responders to Stage 2: AVP-786, Stage 1: Placebo Non-responders to Stage 2: Placebo, Stage 1: Placebo Responders to Stage 2: AVP-786, Stage 1: Placebo Responders to Stage 2: Placebo |
| AVP-786-2828 mg of d6-DM and 4.9 mg of Q | Drug | Overall Study: Stage 1 AVP-786/Stage 2 AVP-786, Stage 1: AVP-786, Stage 1: Placebo Non-responders to Stage 2: AVP-786, Stage 1: Placebo Responders to Stage 2: AVP-786 |
| AVP-786-42.6342.63 mg of d6-DM and 4.9 mg of Q | Drug | Overall Study: Stage 1 AVP-786/Stage 2 AVP-786, Overall Study: Stage 1 Placebo/Stage 2 Placebo or Stage 1 Placebo/Stage 2 AVP-786, Stage 1: AVP-786, Stage 1: Placebo Non-responders to Stage 2: AVP-786, Stage 1: Placebo Responders to Stage 2: AVP-786 |
Primary outcome
Stage 1: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscale of Aggression, Agitation, and Irritability/Lability (NPI-C-3)
Time frame: Baseline to Week 6
NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These are collectively rated first by the informant/caregiver based on frequency (0-4);severity (0-3);informant/caregiver distress (0-5) \& then by the participant based on frequency (0-4), which the clinician then integrates into a (0-3) clinical impression severity rating. NPI-C-3= aggression, agitation, \& irritability/lability subscales. NPI-C agitation domain= sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain= sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain= sum of clinician impression severity scores for irritability/lability questions 1-12 (score=0-36). NPI-C-3 composite score ranges from 0-99. Higher score= increased severity. Least square (LS) mean was analyzed using mixed effects model repeated measures (MMRM) analysis.
Stage 2: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the NPI-C Subscale of NPI-C-3
Time frame: Week 7 to Week 12
NPI-C is a retrospective informant/caregiver interview covering 12 neuropsychiatric symptom domains. These domains are collectively rated by the informant/caregiver based on frequency (0-4), severity (0-3) \& informant/caregiver distress (0-5), then by participant based on frequency (0-4), which is integrated by clinician into (0-3) clinical impression severity rating. NPI-C-3=aggression, agitation, \& irritability/lability subscales. NPI-C agitation domain=sum of clinical impression severity scores for agitation questions 1-13 (score=0-39). NPI-C aggression domain=sum of clinician impression severity scores for aggression questions 1-8 (score=0-24). NPI-C irritability/lability domain=sum of clinician impression severity scores for irritability/lability questions 1-12 (score= 0-36). NPI-C-3 composite score ranges from 0-99. Higher score=increased severity. LS mean was analyzed using MMRM analysis. Overall number analyzed=number of participants with data available for analysis.
8 secondary outcomes
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Aggression
Time frame: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Agitation
Time frame: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Irritability/Lability
Time frame: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in NPI-C Rating Scale Subscale Scores for Disinhibition
Time frame: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in Modified Clinical Global Impression of Severity (mCGI-S) Scale Scores
Time frame: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores
Time frame: Stage 1: Baseline to Week 6; Stage 2: Week 7 to Week 12
Stage 1 and Stage 2: Modified Clinical Global Impression of Change (mCGI-C) Raw Scores
Time frame: Stage 1: Week 6; Stage 2: Week 12
Stage 1 and Stage 2: Patient Global Impression of Change (PGI-C) Raw Scores
Time frame: Stage 1: Week 6; Stage 2: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
54 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AVP-786-28 and AVP-786-42.63 in people with Neurobehavioral Disinhibition, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 54 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Change From Baseline in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscale of Aggression, Agitation, and Irritability/Lability (NPI-C-3) (time frame: Baseline to Week 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2025; AzTrials last refreshed its copy on 8 Nov 2026.