Clinical trial NCT02618408: Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1)
Official title: Assessment of the Efficacy and Safety of Molindone Hydrochloride Extended-Release for the Treatment of Impulsive Aggression in Pediatric Patients With Attention Deficit/Hyperactivity Disorder in Conjunction With Standard ADHD Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Lead sponsor: Supernus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-01
Enrollment: 333
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy and Safety of SPN-810 on the Frequency of Impulsive Aggression (IA) Measured by the Impulsive Aggression Diary
timeFrame: Daily measure from Visit 2 (Week-2) to Visit 6 (Week 5) for a total of 7 weeks
Secondary outcomes:
measure: Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated
timeFrame: Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks
measure: Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S)
timeFrame: 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.
measure: Effect of SPN-810 on Impulsive Aggression Measured by Child Health Questionnaire Parent Form 28-item (CHQ-PF28)
timeFrame: Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.
measure: Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
timeFrame: Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.
measure: Effect of SPN-810 on Impulsive Aggression Measured by the Caregiver Clinical Global Impression - Improvement Scale (CGI-I)
timeFrame: Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks]
measure: Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale
timeFrame: Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.
Other outcomes:
Locations:
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: Culver City
country: United States
facility: ProScience
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists
state: California
city: Orange
country: United States
facility: Neuropsychiatric Research Center of Orange County
state: California
city: Bradenton
country: United States
facility: Meridien Research at Florida Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC.
state: Florida
city: Orlando
country: United States
facility: CNS Healthcare of Orlando
state: Florida
city: Chicago
country: United States
facility: American Medical Research
state: Illinois
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Baltimore
country: United States
facility: Hugo W Moser Research Institute at Kennedy Krieger
state: Maryland
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Columbus
country: United States
facility: Ohio State University Nisonger Center Clinical Trials Program
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals
state: Oklahoma
city: Gresham
country: United States
facility: Cyn3rgy Research
state: Oregon
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Memphis
country: United States
facility: CNS Healthcare
state: Tennessee
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Dallas
country: United States
facility: Relaro Medical Trials
state: Texas
city: Houston
country: United States
facility: Bayou City Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of the Woodlands
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Richmond
country: United States
facility: Alliance Research Group, LLC.
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
Study officials:
affiliation: Supernus Pharmaceuticals, Inc.
name: Azmi Nasser, PhD
role: STUDY_DIRECTOR
References: