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

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ClinicalTrials.gov Identifier: NCT03095066
Recruitment Status : Recruiting
First Posted : March 29, 2017
Last Update Posted : June 23, 2022
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Neurobehavioral Disinhibition Drug: AVP-786 Drug: Placebo Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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).
Actual Study Start Date : May 30, 2017
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: AVP-786
Dose 1 capsules administered twice a day over a 12-week period
 Drug: AVP-786
oral capsules

Drug: Placebo
oral capsules
Placebo Comparator: Placebo
Placebo capsules administered twice a day over a 12-week period
 Drug: Placebo
oral capsules


Outcome Measures
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Primary Outcome Measures :
  1. Change from Baseline to Week 12 in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscales of Aggression, Agitation, and Irritability/Lability (NPI-C-3) [ Time Frame: Baseline; Week 12 ]
    The NPI-C can be used to rate the presence of neuropsychiatric symptoms across 14 domains. The scores for each item within an individual domain/subscale range from 0 to 3, with a higher score indicating increased severity. The NPI-C-3 is comprised of the aggression, agitation, and irritability/lability subscales. The scores for the three subscales are summed to create the total NPI-C-3 composite score, which ranges from 0 to 99, with a higher score indicating increased severity.


Secondary Outcome Measures :
  1. Change from Baseline to Week 12 in Modified Clinical Global Impression of Change (mCGI-C) Raw Scores [ Time Frame: Baseline; Week 12 ]
    The mCGI-C will be used to assess the clinician's general impression of the participant's treatment response. The mCGI-C is a 7-point (1 to 7) modified version of the CGI-C scale. A higher score represents worsening of symptoms.

  2. Change from Baseline to Week 12 in NPI-C Rating Scale Subscales Scores for Aggression, Agitation, Irritability/Lability, and Disinhibition [ Time Frame: Baseline; Week 12 ]
    The NPI-C is used to rate the presence of neuropsychiatric symptoms across 14 domains. The scores for each item within an individual domain/subscale range from 0 to 3, with a higher score indicating increased severity.

  3. Change from Baseline to Week 12 in Modified Clinical Global Impression of Severity (mCGI-S) Scale Scores [ Time Frame: Baseline; Week 12 ]
    The mCGI-S will be used to assess the clinician's view of the participant's severity of aggression, agitation, and irritability symptoms. The mCGI-S is a 7-point (1 to 7) modified version of the CGI-S scale. In all cases, a higher score represents increased severity.

  4. Change from Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) Scores [ Time Frame: Baseline; Week 12 ]
    The PGI-S is a single-question scale that specifically assesses the severity of symptoms of neurobehavioral disinhibition, including aggression, agitation, and irritability, on a 7-point scale : 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.

  5. Change from Baseline to Week 12 in Patient Global Impression of Change (PGI-C) Raw Scores [ Time Frame: Baseline; Week 12 ]
    The PGI-C is a 7-point (1 to 7) scale used to assess the participant's assessment of treatment response. A higher score indicates worsening of the symptoms.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with traumatic brain injury (TBI)
  • Participants with neurobehavioral disinhibition symptoms that are present after trauma or after recovery of consciousness
  • Score of ≥4 on the modified Clinical Global Impression of Severity (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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03095066


Contacts
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Contact: Clinical Transparency 240-683-3421 smb_clinicaltranspa@otsuka-us.com

Locations
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Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
More Information
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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT03095066    
Other Study ID Numbers: 17-AVP-786-205
First Posted: March 29, 2017    Key Record Dates
Last Update Posted: June 23, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
URL: https://clinical-trials.otsuka.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
aggression
agitation
irritability
non-penetrating brain injury
 traumatic brain injury
TBI
AVP-786
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Psychomotor Agitation
Aggression
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Craniocerebral Trauma
Trauma, Nervous System
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Behavioral Symptoms