Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1)
Condition: Attention Deficit Hyperactivity Disorder (ADHD)
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Aggression
Intervention: SPN-810 (18 mg); SPN-810 (36 mg); Placebo
Intervention description: 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.; 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.; 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 333.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No

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.
    

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.