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

NCT ID: NCT02618408

Last Updated: 2024-01-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

333 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-25

Study Completion Date

2019-10-24

Brief Summary

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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.

Detailed Description

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This is a multicenter, randomized, double-blind, placebo-controlled, 3-arm, parallel-group study, to assess the efficacy, safety, and tolerability of SPN-810 in the treatment of IA in subjects 6 to 12 years old with ADHD, in conjunction with standard ADHD treatment.

Conditions

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Attention Deficit Hyperactivity Disorder (ADHD)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Low dose SPN-810 (18 mg)

Oral

Group Type EXPERIMENTAL

SPN-810 (18 mg)

Intervention Type 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.

High dose SPN-810 (36 mg)

Oral

Group Type EXPERIMENTAL

SPN-810 (36 mg)

Intervention Type 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.

Placebo

Oral

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

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SPN-810 (18 mg)

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.

Intervention Type DRUG

SPN-810 (36 mg)

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Healthy male or female subjects, age 6 to 12 years at the time of screening.
2. 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).
3. Retrospective Modified Overt Aggression Scale (R-MOAS) score of ≥24 at screening.
4. CGI-S score of at least moderately ill at both Screening and Randomization.
5. Vitiello Aggression Scale score from -2 to -5 at screening.
6. Free of antipsychotic medication for at least two weeks prior to Visit 2.
7. 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.
8. 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.
9. Medically healthy and with clinically normal laboratory profiles, vital signs, and electrocardiograms (ECGs).
10. Weight of at least 20 kg.
11. Able and willing to swallow tablets whole and not chewed, cut, or crushed.
12. Written Informed Consent obtained from the subject's parent or legal representative and written Informed Assent obtained from the subject if appropriate.
13. Measurement of compliance ≥ 80% for completion of IA Diary during Baseline Period.

Exclusion Criteria

1. Body Mass Index (BMI) in 99th percentile or above.
2. 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.
3. 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.
4. 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.
5. Use of herbal supplements within one week of Visit 2.
6. Known or suspected intelligence quotient (IQ) \< 70.
7. Unstable endocrinological or neurological conditions which confound the diagnosis or are a contraindication to treatment with antipsychotics.
8. 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.
9. Pregnancy or refusal to practice contraception during the study (for female subjects of childbearing potential and sexually active males).
10. Substance or alcohol use during the last three months.
11. Urine drug test at screening that is positive for alcohol or drugs of abuse.
12. Known allergy or sensitivity to molindone hydrochloride.
13. 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.
14. Use of an investigational drug or participation in an investigational study within 30 days prior to Visit 2.
Minimum Eligible Age

6 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Supernus Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Azmi Nasser, PhD

Role: STUDY_DIRECTOR

Supernus Pharmaceuticals, Inc.

Locations

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Woodland Research Northwest

Rogers, Arkansas, United States

Site Status

ProScience

Culver City, California, United States

Site Status

Behavioral Research Specialists

Glendale, California, United States

Site Status

Neuropsychiatric Research Center of Orange County

Orange, California, United States

Site Status

Meridien Research at Florida Clinical Research Center

Bradenton, Florida, United States

Site Status

Sarkis Clinical Trials

Gainesville, Florida, United States

Site Status

Florida Clinical Research Center, LLC.

Maitland, Florida, United States

Site Status

CNS Healthcare of Orlando

Orlando, Florida, United States

Site Status

American Medical Research

Chicago, Illinois, United States

Site Status

Capstone Clinical Research

Libertyville, Illinois, United States

Site Status

Psychiatric Associates

Overland Park, Kansas, United States

Site Status

Hugo W Moser Research Institute at Kennedy Krieger

Baltimore, Maryland, United States

Site Status

Finger Lakes Clinical Research

Rochester, New York, United States

Site Status

Ohio State University Nisonger Center Clinical Trials Program

Columbus, Ohio, United States

Site Status

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, United States

Site Status

Paradigm Research Professionals

Oklahoma City, Oklahoma, United States

Site Status

Cyn3rgy Research

Gresham, Oregon, United States

Site Status

Carolina Clinical Trials, Inc.

Charleston, South Carolina, United States

Site Status

CNS Healthcare

Memphis, Tennessee, United States

Site Status

Research Strategies of Memphis, LLC

Memphis, Tennessee, United States

Site Status

Relaro Medical Trials

Dallas, Texas, United States

Site Status

Bayou City Research Corporation

Houston, Texas, United States

Site Status

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States

Site Status

Road Runner Research

San Antonio, Texas, United States

Site Status

Family Psychiatry of the Woodlands

The Woodlands, Texas, United States

Site Status

Aspen Clinical Research

Orem, Utah, United States

Site Status

Alliance Research Group, LLC.

Richmond, Virginia, United States

Site Status

Seattle Children's Research Institute

Seattle, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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810P301

Identifier Type: -

Identifier Source: org_study_id

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