Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 2)
- Conditions
- Attention Deficit Hyperactivity Disorder (ADHD)
- Interventions
- Drug: PlaceboDrug: SPN-810 (18 mg)Drug: SPN-810 (36 mg)
- Registration Number
- NCT02618434
- Lead Sponsor
- Supernus Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study is to demonstrate the efficacy, safety, and tolerability of SPN-810 in the treatment of impulsive aggression in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) in conjunction with standard ADHD treatment. Approximately 297 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 study is a randomized, placebo-controlled, double-blind, multicenter, parallel group, fixed dose study to demonstrate the efficacy, safety, and tolerability of SPN-810 in the treatment of IA in subjects aged 6 to 12 years with ADHD in conjunction with standard ADHD treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 297
- Otherwise healthy male or female subjects, age 6 to 12 years at the time of screening with a primary diagnosis of ADHD and currently receiving monotherapy treatment with an optimized FDA-approved ADHD medication.
- Impulsive aggression will be confirmed at screening using R-MOAS and Vitiello Aggression Scale.
- 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 criteria for autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorder, or any other anxiety disorder as the primary diagnosis.
- Known or suspected intelligence quotient (IQ) < 70, suicidality, pregnancy, or substance or alcohol abuse.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Oral Low dose SPN-810 (18 mg) SPN-810 (18 mg) Oral High dose SPN-810 (36 mg) SPN-810 (36 mg) Oral
- Primary Outcome Measures
Name Time Method Efficacy and Safety of SPN-810 on the Frequency of Impulsive Aggression (IA) Measured by the Impulsive Aggression Diary Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks 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.
- Secondary Outcome Measures
Name Time Method 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 The Clinical Global Impression - Improvement Scale (CGI-I) is an assessment of how much the patient's illness has improved or worsened relative to a baseline state at the beginning of treatment.
CGI-I was evaluated by the Investigator at each visit on a 7-point scale with 1=very much improved, 2= much improved, 3= minimally improved, 4= no change, 5= minimally worse, 6= much worse, 7= very much worseEffect 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. 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 three time points: Visit 4 (Week 1); Visit 5 (Week 2) and Visit 6 (Week 5).
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. The PSI-4-SF is a 36-item self-report measure of parenting stress. Three subscales Parental Distress (PD), Parent-Child Dysfunctional Interaction (P-CDI), and Difficult Child (DC) consist of 12 items each. Parent chooses one of the 5 responses against each item. The 5 responses are: Strongly Agree (SA), Agree (A), Not Sure (NS), Disagree (D), and Strongly Disagree (SD) to indicate the degree to which they agree with each statement. The PD subscale raw score ranges from 12-60, P-CDI and DC each subscale raw score ranges from 16-56. The total stress raw score is the sum of the three subscales (PD+P-CDI+ DC) with a minimum score of 44 and a maximum score of 172. The total stress score is then converted into the percentile score. Parents with a 91st percentile or higher are experiencing clinically significant levels of stress. Data represents the mean change in percentile score from Baseline (Visit 3) and one time point, Visit 6 (Week 5).
Effect of SPN-810 on Impulsive Aggression Measured by the Percentage of Responders Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks A Responder was defined as a subject with at least a 30% or 50% reduction in the frequency of IA behaviors per 7 days in the Treatment (Titration and Maintenance) period relative to the Baseline period per the IA Diary.
Data represent the percentage of subjects with 30% and 50% reduction in IA behaviors from Baseline to end of treatment period.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. The CHQ-PF28 is a short generic measure of health status and health-related quality of life. The 28 items have 4, 5, or 6 response options, divided over 8 multi-item scales (physical functioning, general behavior, mental health, self-esteem, general health perceptions, parental impact: emotional, parental impact: time, and family activities) and 5 single item concepts (role functioning: emotional/behavior, role functioning: physical, bodily pain, family cohesion, and change in health). In addition, the individual scale scores will be aggregated to derive 2 summary component scores: the physical functioning and psychosocial health summary scores. The range on subscales and the overall scale is 0-100 (0 = worst possible health state; 100 = best possible health state).
Data represent the change from Baseline (Visit 3) to one time point, Visit 6 (Week 5).Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Caregiver Rated Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks The CGI scale was developed to provide a brief, stand-alone assessment of the clinician's view of a subjects' global functioning prior to and after administration of a study medication. The scale was also rated by the Caregiver to assess the improvement of IA behaviors.
. CGI-I was evaluated by the Caregiver at each visit on a 7-point scale with 1=very much improved, 2= much improved, 3= minimally improved, 4= no change, 5= minimally worse, 6= much worse, 7= very much worseEffect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. The Swanson, Nolan, Pelham Rating Scale-Revised (SNAP-IV) includes 18 ADHD and 8 oppositional defiant disorder (ODD) symptoms. The symptoms are scored on a 4-point scale, not at all=0, just a little=1, Quite a bit= 2, very much=3. The ratings from the SNAP-IV scale are grouped into the following 4 subscales: ADHD Inattention (items #1-9), ADHD Hyperactivity/Impulsivity (items#10-18), ODD (items# 19-26), and ADHD-combined (first two scales combined, items #1-18). Each observed subscale score is the average rating of the items scores for the subscale where scores range from 0-3; the higher is the score, worsen is the outcome.
Data represent the change of the observed scores between Baseline (Visit 3) and the end of the study, Visit 6 (Week 5).
Trial Locations
- Locations (31)
Gulfcoast Clinical Research Center
🇺🇸Fort Myers, Florida, United States
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
Pedia Research
🇺🇸Owensboro, Kentucky, United States
Louisiana State University Health Sciences Center
🇺🇸Shreveport, Louisiana, United States
St. Charles Psychiatric Associates Midwest Research Center
🇺🇸Saint Charles, Missouri, United States
Quality Clinical Research
🇺🇸Omaha, Nebraska, United States
Metropolitan Neuro Behavioral Institute
🇺🇸Chandler, Arizona, United States
Woodland International Research Group
🇺🇸Little Rock, Arkansas, United States
Sun Valley Research Center
🇺🇸Imperial, California, United States
ASCLEPES Research Center
🇺🇸Panorama City, California, United States
Alliance for Wellness dba Alliance for Research
🇺🇸Long Beach, California, United States
MCB Clinical Research Centers, LLC
🇺🇸Colorado Springs, Colorado, United States
Children's National Medical Center/Children's Research Institute
🇺🇸Washington, District of Columbia, United States
Indago Research & Health Center, Inc.
🇺🇸Hialeah, Florida, United States
Innovative Clinical Research, Inc
🇺🇸Lauderhill, Florida, United States
Laszlo J. Mate, M.D., P.A.
🇺🇸North Palm Beach, Florida, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States
iResearch Atlanta
🇺🇸Decatur, Georgia, United States
Advanced Clinical Research
🇺🇸Meridian, Idaho, United States
AMR Conventions Research
🇺🇸Naperville, Illinois, United States
Alivation Research, LLC
🇺🇸Lincoln, Nebraska, United States
Hassmann Research Institute
🇺🇸Berlin, New Jersey, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
InSite Clinical Research
🇺🇸DeSoto, Texas, United States
Houston Clinical Trials
🇺🇸Houston, Texas, United States
Ericksen Research & Development
🇺🇸Clinton, Utah, United States
Pacific Institute of Medical Sciences
🇺🇸Bothell, Washington, United States
University of South Florida- Dept. of Psychiatry and Neurosciences
🇺🇸Tampa, Florida, United States
University of Cincinnati Department of Psychiatry and Behavioral Neuroscience
🇺🇸Cincinnati, Ohio, United States
APG Research, LLC
🇺🇸Orlando, Florida, United States
BioBehavioral Research of Austin P.C.
🇺🇸Austin, Texas, United States