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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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.