Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1)

NCT02618408 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 810P301
• Study Type: interventional
• Target: 333
• Locations: 1 country
• Sites: 28

Brief Summary

The purpose of this study is to demonstrate the efficacy, safety, and tolerability of SPN-810 in the treatment of Impulsive Aggression (IA) in subjects with Attention-Deficit/Hyperactivity Disorder (ADHD) in conjunction with standard ADHD treatment. Approximately 426 subjects aged 6 to 12 years with ADHD and comorbid impulsive aggression will be recruited in this study. The frequency of impulsive aggression behaviors will be assessed as a primary outcome. Additionally, the severity and improvement in impulsive aggression and quality of life measures for the subject and caregiver will be assessed using validated scales.

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Outcome Measures

Primary Outcomes (1)

• Efficacy and Safety of SPN-810 on the Frequency of Impulsive Aggression (IA) 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 6, 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 (Week-2) to Visit 6 (Week 5) for a total of 7 weeks

Secondary Outcomes (6)

• Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated

  Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks

• Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S)

  Baseline/Visit 3 (Day 1), Visit 4 (Week 1), Visit 5 (Week 2), and Visit 6 (Week 5). The total duration of the study was 5 weeks.

• Effect of SPN-810 on Impulsive Aggression Measured by Child Health Questionnaire Parent Form 28-item (CHQ-PF28)

  Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.

• Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)

  Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.

• Effect of SPN-810 on Impulsive Aggression Measured by the Caregiver Clinical Global Impression - Improvement Scale (CGI-I)

  Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks]

Study Arms (3)

Low dose SPN-810 (18 mg)

EXPERIMENTAL

Oral

Drug: SPN-810 (18 mg)

High dose SPN-810 (36 mg)

EXPERIMENTAL

Oral

Drug: SPN-810 (36 mg)

Placebo

PLACEBO COMPARATOR

Oral

Drug: Placebo

Interventions

SPN-810 (18 mg) DRUG

Subjects were randomized to receive SPN-810 low dose (18 mg) twice each day (BID) with or without food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if after noon, the evening dose.

Low dose SPN-810 (18 mg)

SPN-810 (36 mg) DRUG

Subjects were randomized to receive SPN-810 high dose (36 mg) twice each day (BID) with or without food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if after noon, the evening dose.

High dose SPN-810 (36 mg)

Placebo DRUG

Subjects were randomized to receive Placebo twice each day (BID) with or without food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if after noon, the evening dose.

Placebo

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Healthy male or female subjects, age 6 to 12 years at the time of screening.
• Diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Disorders- 5 (DSM-5 confirmed by the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime Version 2013 (K-SADS-PL 2013).
• Retrospective Modified Overt Aggression Scale (R-MOAS) score of ≥24 at screening.
• CGI-S score of at least moderately ill at both Screening and Randomization.
• Vitiello Aggression Scale score from -2 to -5 at screening.
• Free of antipsychotic medication for at least two weeks prior to Visit 2.
• Monotherapy treatment with FDA-approved optimized ADHD medication (psychostimulant or non-stimulant) at an FDA-approved dose for at least one month prior to screening, and willing to maintain that dose throughout the Baseline and Treatment period.
• α 2- adrenergic agonists (e.g., clonidine and guanfacine) used for any other reason except for monotherapy treatment for ADHD (e.g., aggression or insomnia) must be discontinued at least two weeks prior to Visit 2.
• Medically healthy and with clinically normal laboratory profiles, vital signs, and electrocardiograms (ECGs).
• Weight of at least 20 kg.
• Able and willing to swallow tablets whole and not chewed, cut, or crushed.
• Written Informed Consent obtained from the subject's parent or legal representative and written Informed Assent obtained from the subject if appropriate.
• Measurement of compliance ≥ 80% for completion of IA Diary during Baseline Period.

You may not qualify if:

• Body Mass Index (BMI) in 99th percentile or above.
• Current or lifetime diagnosis of epilepsy, major depressive disorder, bipolar disorder, schizophrenia or a related disorder, personality disorder, Tourette's disorder, or psychosis not otherwise specified.
• Currently meeting DSM-5 criteria for autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorder, or any other anxiety disorder as the primary diagnosis.
• Use of anticonvulsants including carbamazepine and valproic acid, antidepressants, mood stabilizers including lithium, benzodiazepines, cholinesterase inhibitors, or any drug known to inhibit CYP2D6 activity within two weeks of Visit 2.
• Use of herbal supplements within one week of Visit 2.
• Known or suspected intelligence quotient (IQ) \< 70.
• Unstable endocrinological or neurological conditions which confound the diagnosis or are a contraindication to treatment with antipsychotics.
• Suicidality, defined as either active suicidal plan/intent or active suicidal thoughts in the six months before the Screening Visit or more than one-lifetime suicide attempt.
• Pregnancy or refusal to practice contraception during the study (for female subjects of childbearing potential and sexually active males).
• Substance or alcohol use during the last three months.
• Urine drug test at screening that is positive for alcohol or drugs of abuse.
• Known allergy or sensitivity to molindone hydrochloride.
• Any reason which, in the opinion of the Investigator or the Sponsor, would prevent the subject and subject's caregiver from participating in the study or complying with the study procedures.
• Use of an investigational drug or participation in an investigational study within 30 days prior to Visit 2.

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (28)

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

Location

ProScience

Culver City, California, 90230, United States

Location

Behavioral Research Specialists

Glendale, California, 91206, United States

Location

Neuropsychiatric Research Center of Orange County

Orange, California, 92868, United States

Location

Meridien Research at Florida Clinical Research Center

Bradenton, Florida, 34201, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Florida Clinical Research Center, LLC.

Maitland, Florida, 32751, United States

Location

CNS Healthcare of Orlando

Orlando, Florida, 32801, United States

Location

American Medical Research

Chicago, Illinois, 60617, United States

Location

Capstone Clinical Research

Libertyville, Illinois, 60048, United States

Location

Psychiatric Associates

Overland Park, Kansas, 66211, United States

Location

Hugo W Moser Research Institute at Kennedy Krieger

Baltimore, Maryland, 21205, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Ohio State University Nisonger Center Clinical Trials Program

Columbus, Ohio, 43210, United States

Location

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, 73112, United States

Location

Paradigm Research Professionals

Oklahoma City, Oklahoma, 73118, United States

Location

Cyn3rgy Research

Gresham, Oregon, 97030, United States

Location

Carolina Clinical Trials, Inc.

Charleston, South Carolina, 29407, United States

Location

CNS Healthcare

Memphis, Tennessee, 38119, United States

Location

Research Strategies of Memphis, LLC

Memphis, Tennessee, 38119, United States

Location

Relaro Medical Trials

Dallas, Texas, 75243, United States

Location

Bayou City Research Corporation

Houston, Texas, 77006, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Road Runner Research

San Antonio, Texas, 78258, United States

Location

Family Psychiatry of the Woodlands

The Woodlands, Texas, 77381, United States

Location

Aspen Clinical Research

Orem, Utah, 84058, United States

Location

Alliance Research Group, LLC.

Richmond, Virginia, 23230, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98121, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Limitations and Caveats

There were no limitations or caveats with the clinical trial.

Results Point of Contact

• Title: Gianpiera Ceresoli-Borroni, PhD, Director of Clinical Research
• Organization: Supernus

gceresoliborroni@supernus.com

301-838-2521

Study Officials

• Azmi Nasser, PhD

  Supernus Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: December 1, 2015
• Study Start: January 25, 2016
• Primary Completion: September 4, 2019
• Study Completion: October 24, 2019
• Last Updated: January 2, 2024
• Results First Posted: November 1, 2022

Record last verified: 2020-11

Locations

US (28)