Phase 2a Study of Safety and Tolerability of SPN-810 in Children With ADHD and Persistent Serious Conduct Problems

Phase 2

Completed

Conditions: Attention Deficit Disorder With Hyperactivity
Conduct Disorder

Interventions: Drug: SPN-810

Registration Number: NCT00626236

Lead Sponsor: Supernus Pharmaceuticals, Inc.

Brief Summary: The primary objective was to evaluate the safety and tolerability of four doses of SPN-810 in children with ADHD and persistent serious conduct problems.

Detailed Description: This will be a randomized, multicenter, parallel group, dose-ranging safety and tolerability study in children with ADHD and persistent serious conduct problems. The target subjects are healthy male or female children aged 6 to 12 years, inclusive, with a diagnosis of ADHD with persistent serious conduct problems. To determine eligibility for the study, subjects will undergo an initial screening visit. Seventy-two subjects will be randomized in the study; assuming a 17% dropout rate, it is anticipated that 60 subjects will complete the study. The study will consist of a Screening Period (within 28 days prior to the first dose administration), a Titration Period of 2 to 5 weeks, a Maintenance Period of 6 weeks, and a Safety Follow-up, which will be performed 30 days after the final study visit. The total subject duration in the study will be 16 to 19 weeks depending on the treatment group assignment. The total study duration is anticipated to be 15.5 months. A total of 72 subjects will be randomized based on weight at baseline, to 1 of 4 treatment groups.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 78

Inclusion Criteria

Healthy pediatric male or female subjects, age 6 to 12 years.
Diagnostic and Statistical Manual of Mental Disorders - IV -Text Revision (DSM-IV-TR) diagnosis of ADHD.
NCBRF-TIQ disruptive behavior disorder subscale 27 or greater at baseline; AND a score of 2 or more on at least 1 of the following 3 items of the conduct problem subscale: knowingly destroys property, gets in physical fights, physically attacks people.
IQ greater than 71.

Exclusion Criteria

Current or lifetime diagnosis of bipolar disorder, post-traumatic stress disorder, personality disorder, or psychosis not otherwise specified.
Currently meeting DSM-IV-TR criteria for major depressive disorder, obsessive compulsive disorder, or pervasive developmental disorder.
Any other anxiety disorder as primary diagnosis.
Use of anticonvulsants, antidepressants, lithium, carbamazepine, valproic acid, or cholinesterase inhibitors within 2 weeks of baseline.
Unstable endocrinological or neurological conditions which confound the diagnosis or are a contraindication to treatment with antipsychotics.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment 1	SPN-810	Treatment 1: SPN-810 5mg/day for subjects \<30kg and 10mg/day for subjects ≥30kg
Treatment 2	SPN-810	Treatment 2: SPN-810 10mg/day for subjects \<30kg and 20mg/day for subjects ≥30kg.
Treatment 3	SPN-810	Treatment 3: SPN-810 15mg/day for subjects \<30kg and 30mg/day for subjects ≥30kg.
Treatment 4	SPN-810	Treatment 4: SPN-810 20mg/day for subjects \<30kg and 40mg/day for subjects ≥30kg.

Primary Outcome Measures

Name	Time	Method
The Nisonger Child Behavior Rating Form- Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem Subscale Score	Weekly visits starting from Visit 1 (Week 1) to Visit 12 (12 weeks)	The Nisonger Child Behavior Rating Form (NCBRF) is an instrument designed to assess the behavior of children with intellectual or developmental disabilities. The NCBRF-TIQ is a 66-item behavior rating form designed to assess the behavior of children and adolescents with typical development. The NCBRF is made up of three sections: I, Where raters can identify unusual circumstances that may have affected the youth's behavior; II, where positive behaviors are rated, and III, a listing of problem behaviors. There are separate Teacher and Parent versions of the form, and the NCBRF takes about 15 minutes to complete. The NCBRF is designed to be used with children and adolescents ages 3 to 16 years. The lowest score is a "0" and the highest score is "198". A higher score of the Conduct Problem Subscale score means a worse outcome. A change or negative score means improvement. Data represent the change from baseline (Visit 1) and 11 time points (Visit 2 to Visit 12).

Secondary Outcome Measures

Name	Time	Method
The Changes From Baseline in the CGI-S	Weekly visits starting from Visit 1 (Week 1) to Visit 12 (12 weeks)	The CGI scale was developed to provide a brief, stand-alone assessment of the clinician's view of a subject's global functioning prior to and after the administration of study medication. The severity of illness (CGI-S) is rated by the investigator 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 from baseline (Visit 1) and 11 time points (Visit 2 to Visit 12). A lower overall score in subsequent testing indicates successful therapy.
Clinical Global Impression - Improvement Scale (CGI-I)	Weekly visits starting from Visit 1 (Week 1) to Visit 12 (12 weeks)	Clinical Global Impression Scale. CGI-I is measured relative to the condition at the Baseline 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, and 7=Very much worse. A lower overall score in subsequential testing indicates successful treatment. Data represent the change from baseline (Visit 1) and 11 time points (Visit 2 to Visit 12).
SNAP-IV ADHD Inattention	Weekly visits starting from Visit 1 (Week 1) to Visit 12 (12 weeks)	The ratings from the SNAP-IV scale are grouped into the following 3 subscales: ADHD-Inattention (items #1-9), ADHD-Hyperactivity/Impulsivity (items #10-18), and ADHD combined (items #0-18) Subscales. The symptoms are scored on a 4-point scale. Each subscale score is the average rating of the items scores for the subscale. For the inattention subscale, the scores range from 0-27, the higher the score, the worse the outcome. A decrease in score means improvement. Data represent the change between Baseline (Visit 1) to Visit 2, Visit 4, Visit 6, Visit 10 and Visit 12.
SNAP-IV Subscales ADHD Hyperactivity/Impulsivity	Weekly visits starting from Visit 1 (Week 1) to Visit 12 (12 weeks)	The ratings from the SNAP-IV scale are grouped into the following 3 subscales: ADHD-Inattention (items #1-9), ADHD-Hyperactivity/Impulsivity (items #10-18), and ADHD combined (items #1-18) Subscales. The symptoms are scored on a 4-point scale. Each subscale score is the average rating of the items scores for the subscale. For the Hyperactivity/Impulsivity subscale, the scores range from 0-27, the higher the score, the worse the outcome. A decrease in score means improvement. Data represent the change between Baseline (Visit 1) to Visit 2, Visit 4, Visit 6, Visit 10 and Visit 12.
SNAP-IV Subscales - ADHD Combined	Weekly visits starting from Visit 1 (Week 1) to Visit 12 (12 weeks)	The ratings from the SNAP-IV scale are grouped into the following 3 subscales: ADHD-Inattention (items #1-9), ADHD-Hyperactivity/Impulsivity (items #10-18), and ADHD combined (items #1-18) Subscales. The symptoms are scored on a 4-point scale. Each subscale score is the average rating of the items scores for the subscale. For the combined subscale, the scores range from 0-54, the higher the score, the worse the outcome. A decrease in score means improvement. Data represent the change between Baseline (Visit 1) to Visit 2, Visit 4, Visit 6, Visit 10 and Visit 12.

Trial Locations

Locations (9): Florida Clinical Research Center
🇺🇸
Bradenton, Florida, United States
Sarkis Clinical Trials
🇺🇸
Gainesville, Florida, United States
CNS Healthcare
🇺🇸
Orlando, Florida, United States
Capstone Clinical Research
🇺🇸
Libertyville, Illinois, United States
The Psychopharm Research Cntr - LSU Dept of Psychiatry
🇺🇸
Shreveport, Louisiana, United States
IPS Research
🇺🇸
Oklahoma City, Oklahoma, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸
Memphis, Tennessee, United States
Alliance Research Group
🇺🇸
Richmond, Virginia, United States
Northwest Clinical Trials
🇺🇸
Bellevue, Washington, United States
Florida Clinical Research Center
🇺🇸Bradenton, Florida, United States