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

Purpose

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

  • Neurobehavioral Disinhibition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Stage 1: Placebo 		Participants will receive AVP-786 matching placebo capsules, orally, twice daily (BID) during Weeks 1 to 6 of the Stage 1 treatment period.
  • Drug: Placebo
    Administered as capsules
Experimental
AVP-786 		Participants will receive AVP-786-28/4.9 (deudextromethorpan 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.
  • Drug: AVP-786-28
    28 mg of d6-DM and 4.9 mg of Q
  • Drug: AVP-786-42.63
    42.63 mg of d6-DM and 4.9 mg of Q
Placebo Comparator
Stage 1: Placebo Non-responders to Stage 2: Placebo 		Participants who will be randomized to receive placebo in Stage 1 and will be classified as non-responders (responders" if modified Clinical Global Impression of Severity [mCGI-S] score is ≤ 3 at Day 43 and Neuropsychiatric Inventory Clinician (NPI-C)-3 score has decreased by ≥ 25% from baseline. Participants who will not meet these criteria will be considered "non-responders) after Week 6 will be re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period.
  • Drug: Placebo
    Administered as capsules
Experimental
Stage 1: Placebo Non-responders to Stage 2: AVP-786 		Participants who will be randomized randomized to receive placebo in Stage 1 and will be 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 will not meet these criteria will be considered "non-responders) after Week 6 will be re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 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.
  • Drug: Placebo
    Administered as capsules
  • Drug: AVP-786-28
    28 mg of d6-DM and 4.9 mg of Q
  • Drug: AVP-786-42.63
    42.63 mg of d6-DM and 4.9 mg of Q
Placebo Comparator
Stage 1: Placebo Responders to Stage 2: Placebo 		Participants who will be randomized to receive placebo in Stage 1 and will be 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 will be re-randomized to continue receiving AVP-786 matching placebo capsules, orally, BID during Weeks 7 to 12 of the Stage 2 treatment period.
  • Drug: Placebo
    Administered as capsules
Experimental
Stage 1: Placebo Responders to Stage 2: AVP-786 		Participants who will be randomized to receive placebo in Stage 1 and will be 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 will be re-randomized to receive AVP-786 in Stage 2 using the same dose escalation schedule used in Stage 1 i.e., AVP-786-28/4.9 capsule, along with AVP-786 matching placebo capsule, orally, QD during Week 7 followed by AVP-786-28/4.9 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.
  • Drug: Placebo
    Administered as capsules
  • Drug: AVP-786-28
    28 mg of d6-DM and 4.9 mg of Q
  • Drug: AVP-786-42.63
    42.63 mg of d6-DM and 4.9 mg of Q

More Details

Status
Completed
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Contact

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.