Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Intermittent Explosive Disorder

NCT03420222 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-AVP-786-206
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 9

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate AVP-786 for the treatment of Intermittent Explosive Disorder (IED).

Conditions

Intermittent Explosive Disorder

Keywords

Intermittent Explosive Disorder; AVP-786

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Overt Aggression Scale - Modified for Outpatient Use (OAS-M) Total Aggression Score at Week 12

  The OAS-M is a clinical-administered instrument designed to assess various manifestations of aggressive behavior through 2 domains: aggression and irritability. The OAS-M aggression domain includes 4 items: verbal assault, assault against objects, assault against others, and assault against self. The rater determines the frequency of each response (item) during the past week, and the frequency of each item is multiplied by the severity level (0 to 5), producing a raw score. This raw score is multiplied by severity weight for that item (verbal assault x 1, assault against objects x 2, assault against others x 3, and assault against self x 3). Each response is scored using a 6-point scale (0 = no events to 5 = most severe form of assault within that category). The weighted individual item scores are added to obtain the OAS-M Total Aggression score. Higher scores indicate increased aggression.

  Baseline; Week 12

Secondary Outcomes (16)

• Change From Baseline in the OAS-M Total Irritability Score at Week 12

  Baseline; Week 12

• Change From Baseline in the OAS-M Individual Items for Aggression at Week 12

  Baseline; Week 12

• Change From Baseline in the OAS-M Individual Items for Irritability at Week 12

  Baseline; Week 12

• Change From Baseline in the Number of Intermittent Explosive Disorder (IED) Days Documented by Participants at Week 12

  Baseline; Week 12

• Change From Baseline in the Number of IED Days as Assessed by the Investigator at Week 12

  Baseline; Week 12

Study Arms (2)

AVP-786

EXPERIMENTAL

Participants were to receive AVP-786-28 (deudextromethorphan hydrobromide \[d6-DM\] 28 milligrams \[mg\]/quinidine sulfate \[Q\] 4.9 mg) once daily (OD) for the first 7 days, followed by AVP-786-28 twice daily (BID) for the next 7 days. Beginning on Day 15, participants were to receive AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) BID for 10 weeks.

Drug: AVP-786

Placebo

PLACEBO COMPARATOR

Participants were to receive placebo BID for 12 weeks.

Drug: Placebo

Interventions

AVP-786 DRUG

oral capsules

AVP-786

Placebo DRUG

oral capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of current Intermittent Explosive Disorder (IED) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, as solicited by the Structured Clinical Interview for DSM-5, Clinical Trials Version
• At least 3 IED days (at least 1 IED episode each day, as recorded by the participant) per week for the 2 consecutive weeks directly preceding baseline with 70% compliance during that time frame, as assessed by the investigator
• Score ≥ 12 on the Life History of Aggression scale at screening
• Score ≥ 6 on the Overt Aggression Scale - Modified Total Irritability at screening and baseline
• Score ≥ 4 on the modified Clinical Global Impression of Severity for IED at screening and baseline

You may not qualify if:

• Diagnosis of major depressive disorder within 6 months of screening
• Significant symptoms of a depressive disorder or a Patient Health Questionnaire-9 score ≥ 10 at screening
• Met only the DSM-5 A2 criterion for IED
• Lifetime history of schizophrenia, schizoaffective disorder, bipolar disorder, antisocial personality disorder, neurocognitive disorder, or mental retardation (DSM-5 criteria)
• Recurrent IED episodes that are better explained by another mental disorder or attributable to another medical condition (e.g., head trauma, Alzheimer's disease) or to the physiological effect of a substance (e.g., a drug of abuse, a medication) (DSM-5 criteria)

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (9)

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

University of Chicago Medical Center Clinical Trial Site 2

Chicago, Illinois, 60637, United States

Location

BTC of New Bedford

New Bedford, Massachusetts, 01740, United States

Location

Psychiatric Care and Research Center

O'Fallon, Missouri, 63368, United States

Location

Atlea Research Institute

Las Vegas, Nevada, 89102, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10036, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Research Institute Lindner Center of Hope/University of Cincinnati

Mason, Ohio, 45040, United States

Location

MeSH Terms

Conditions

Disruptive, Impulse Control, and Conduct Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Limitations and Caveats

Due to limited enrollment (N=10), this clinical trial was terminated by the Sponsor.

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2018
• First Posted: February 5, 2018
• Study Start: January 18, 2018
• Primary Completion: December 28, 2018
• Study Completion: December 28, 2018
• Last Updated: May 24, 2022
• Results First Posted: May 24, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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/

Locations

US (9)