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

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

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.

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.

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.