Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment

Assessment of Efficacy and Safety of SPN-810 for the Treatment of Impulsive Aggression (IA) in Adolescent Subjects With Attention Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment

The purpose of this study was to evaluate the effect of SPN-810 for the treatment of impulsive aggression (IA) in adolescents diagnosed with ADHD when taken in conjunction with standard ADHD treatment.

Study Overview

• Status: Terminated
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Placebo; Drug: SPN-810

Detailed Description

This study was an addition to the pediatric studies (CHIME 1 and CHIME 2) to assess the efficacy and safety of SPN-810 in the improvement of impulsive aggression (IA) behaviors in adolescents with ADHD.

SPN-810 was administered in patients diagnosed with ADHD and associated features of IA, who were currently treated with an FDA-approved standard ADHD treatment and displayed persistent IA behaviors. The frequency of impulsive aggressive behaviors was assessed as a primary outcome.

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• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Culver City, California, United States, 90230
      • ProScience
    • Orange, California, United States, 92868
      • Neuropsychiatric Research Center of Orange County
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20310
      • Children's National Medical Center/Children's Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32217
      • Clinical Neuroscience Solutions, Inc
    • Lakeland, Florida, United States, 33805
      • Meridien Research aka Florida Clinical Research Center, LLC
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC.
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • Tampa, Florida, United States, 33613
      • University of South Florida- Dept. of Psychiatry and Neurosciences
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
    • Naperville, Illinois, United States, 60563
      • AMR Conventions Research
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Hugo W Moser Research Institute at Kennedy Krieger
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates Midwest Research Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Alivation Research, LLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassmann Research Institute
  • New York
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Department of Psychiatry and Behavioral Neuroscience
    • Columbus, Ohio, United States, 43210
      • Ohio State University Nisonger Center Clinical Trials Program
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
    • Oklahoma City, Oklahoma, United States, 73118
      • Paradigm Research Professionals
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare
  • Texas
    • Arlington, Texas, United States, 76014
      • Texas Physicians Medical Research Group
    • Austin, Texas, United States, 78759
      • BioBehavioral Research of Austin P.C.
    • Beaumont, Texas, United States, 77702
      • Gaolin Research, LLC
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Houston, Texas, United States, 08009
      • Houston Clinical Trials
    • Houston, Texas, United States, 77061
      • Dicovery MM Services Inc. Houston
    • Lampasas, Texas, United States, 76550
      • FMCScience
    • Missouri City, Texas, United States, 77459
      • Discovery MM Service, Inc. Missouri
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of The Woodlands
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research & Development
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Otherwise, healthy non-smoking, male and females adolescents (12-17 years of age at the time of screening) with a primary diagnosis of ADHD and currently taking an optimized FDA-approved ADHD medication.
• IA confirmed at screening using R-MOAS scale and Vitiello Aggression Questionnaire.

Exclusion Criteria:

• History or current diagnosis of epilepsy, major depressive disorder, bipolar disorder, schizophrenia and other psychotic disorders, personality disorder, Tourette's syndrome or dissociative disorder, autism spectrum disorder, pervasive developmental disorder, obsessive compulsive disorder, post-traumatic stress disorder, or intermittent explosive disorder.
• Currently meeting DSM-5 criteria for pervasive developmental disorder, obsessive compulsive disorder, post-traumatic stress disorder or intermittent explosive disorder.
• Known or suspected intelligence quotient (IQ) <70, active suicidal plan/intent or active suicidal thought, criminal arrest, alcohol or drug use or pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flexible dose of SPN-810; Subjects treated with flexible dose of SPN-810	Drug: SPN-810; Flexible dose
Placebo Comparator: Placebo; Subjects treated with Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of SPN-810 Treatment on the Frequency of Impulsive Aggression (IA) Behaviors Measured by the Impulsive Aggression Diary	The primary efficacy endpoint was percent change (PCHT) in the frequency (unweighted score) of IA behaviors per 7 days in the treatment (titration and maintenance) period relative to the baseline period calculated over the number of days with non-missing IA diary data. PCHT was then calculated as 100 x (T - B)/B, where T and B are IA behavior frequencies per 7 days during the treatment period (from Day 2 through Visit 7, inclusive) and baseline period (Day ≤1), respectively. The IA behavior frequency per 7 days is defined as (SUM/DAY) x 7, where SUM is the total of the IA behaviors reported in the subject IA diary, and DAY is the number of days with a non-missing IA score in the subject IA diary during the specified study period.	Daily measure from Visit 2 (Day -15) to Visit 7 (Day 36) for a total of 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of SPN-810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S)	The Clinical Global Impression - Severity of Illness (CGI-S) is a single item clinician rating of clinician's assessment of the severity of IA behaviors. CGI-S was evaluated by the Investigator at each visit on a 7- point scale with 1=Normal, 2=Borderline ill, 3=Mildly ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, and 7=Extremely ill. Data represent the change between Baseline (Visit 3/Day 1) and four time points: Visit 4 (Day 15); Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36).	From Baseline/Visit 3 (Day 1) to Visit 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29), Visit 7 (Day 36)
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score	R-MOAS scale gauges the severity of aggressive behavior: the frequency of the 16 behaviors is rated over the past week in 4 areas (VE, PH, PR, SE). For each open question in each area, the parent-rated the aggressive behaviors on a scale from 0 to 5 or more times. To each area corresponds a weighted category: Verbal Incidents (VE)=1, Incidents Toward Other (PH)=4, Incidents Involving Property (PR)=2 and Incidents Directed Toward Self (SE)=3. Therefore, the sum of each area yields a maximum weighted score of 20 (VE), 120 (PH), 60 (PR), and 90 (SE). The total score is the sum of the four area scores or 0-290; the higher the score, the more severe the aggressive behavior is. Data represent the total score change between the Baseline (Visit 3/Day 1) and four time points: Visit 4 (Day 15); Visit 5 (Day 22), Visit 6 (Day 29), and Visit 7 (Day 36).	From Baseline/Visit 3 (Day 1) to Visit 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36).
Effect of SPN-810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Remission Rate	The treatment effect on the R-MOAS was assessed to capture the severity of the aggressive behaviors. The remission rate was defined as percentage of subjects with a R-MOAS total score ≤ 10. Data represent the percentage of subjects at four time points during the treatment period: Visit 4 (Day 15); Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36).	Visit 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36)

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Actual): January 22, 2020
• Study Completion (Actual): January 22, 2020

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Aberrant Motor Behavior in Dementia; Aggression; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: 810P503

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No