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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 : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Avanir Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 23, 2017
First Posted Date  ICMJE March 29, 2017
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE May 30, 2017
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
  • 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 view 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.
  • Change from Baseline to Week 12 in NPI-C Rating Scale Subscales Scores [ Time Frame: Baseline; Week 12 ]
    The NPI-C is used to rate the presence of neuropsychiatric symptoms across 14 domains. The clinician will first interview the participant/caregiver to assign a severity rating for each item within an individual domain/subscale; the scores for each item (ranging from 0 to 3, with a higher score indicating increased severity) are then summed to create a total domain score (ranging from 0 to 48). In all cases, a higher score indicates increased severity of symptoms.
  • Change from Baseline to Week 12 in Frontal Systems Behavior (FrSBe) Scale Scores [ Time Frame: Baseline; Week 12 ]
    The FrSBe is a 46-item questionnaire that was designed to assess frontal behavioral syndromes. It provides total scores and scores for three subscales that rate changes noted in everyday behaviors. Each item in each domain is rated on a 5-point Likert scale. The score of each item is summed to create the subscale score, and each subscale score is summed to create the total score (ranging from 46 to 160). In all cases, a higher score represents worsening symptoms/behavior.
  • 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.
  • Change from Baseline to Week 12 in Patient Health Questionnaire-9 (PHQ-9) Scores [ Time Frame: Baseline; Week 12 ]
    The PHQ-9 is a multiple-choice self-report inventory that is used for the evaluation of depression symptoms. Each of the 9 items is scored on a scale from 0 to 3. The total score ranges from 0 to 27. A higher score represents increased severity of depression.
  • Change from Baseline in Zarit Burden Interview (ZBI) Scores [ Time Frame: Baseline; Week 12 ]
    The ZBI is a 22-item scale used to assess the impact of the participant's disabilities on the caregiver's life. For each item on the scale, the caregiver has to indicate how often they felt distressed. The score ranges from 0 to 88. A higher score indicates greater caregiver distress.
  • Change from Baseline to Week 12 in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Dimension Scores [ Time Frame: Baseline; Week 12 ]
    The EQ-5D-5L is a generic questionnaire measuring the health-related quality of life for 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on 1 of 5 levels. A higher score indicates worse quality of life.
  • Change from Baseline to Week 12 in EQ-5D-5L Visual Analog Scale (VAS) Scores [ Time Frame: Baseline; Week 12 ]
    The EQ-5D-5L is a generic questionnaire measuring health-related quality of life. It consists of a VAS measuring self-reported health status. The EQ VAS records the participant's self-rated health on a VAS with a score of 0 to 100. A higher score represents worse health.
  • Change from Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) Assessed using a VAS (PGI-S VAS) Scores [ Time Frame: Baseline; Week 12 ]
    The PGI-S VAS is a single-question VAS that assesses the severity of aggression, agitation, and irritability, on a scale of 0 to 10. A higher score represents increased severity of these symptoms.
  • 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.
  • Change from Baseline to Week 12 in Post-traumatic Headache (PTH) Assessment Questionnaire Scores [ Time Frame: Baseline; Week 12 ]
    The PTH assessment questionnaire consists of 7 questions that characterize headache frequency, severity, intensity, and the impact of headache on activities. The PTH assessment includes a VAS to rate pain from 0 to 10. A higher score on the VAS represents worse pain.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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).
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Neurobehavioral Disinhibition
Intervention  ICMJE
  • Drug: AVP-786
    oral capsules
  • Drug: Placebo
    oral capsules
Study Arms  ICMJE
  • Experimental: AVP-786
    Dose 1 capsules administered twice a day over a 12-week period
    Interventions:
    • Drug: AVP-786
    • Drug: Placebo
  • Placebo Comparator: Placebo
    Placebo capsules administered twice a day over a 12-week period
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 23, 2017)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jurandir Araujo (949) 339-0175 jaraujo@avanir.com
Contact: Nadine Knowles nknowles@avanir.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03095066
Other Study ID Numbers  ICMJE 17-AVP-786-205
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Avanir Pharmaceuticals
Study Sponsor  ICMJE Avanir Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Avanir Pharmaceuticals
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP