Open-Label Study of SPN-812 Administered With Psychostimulants in Children and Adolescents With ADHD

Exclusion Criteria

• •1. Is currently participating in another clinical trial or has participated in a clinical trial within 60 days prior to screening.
• •2. Is a member of the study personnel or of their immediate families, or is a subordinate (or immediate family member of a subordinate) to any of the study personnel.
• •3. Is a female subject who is pregnant, lactating and/or sexually active and not agreeing to use one of the acceptable contraceptive methods throughout the study.
• •4. Has history of severe drug allergy or hypersensitivity, or known hypersensitivity, to the study medication (SPN-812).
• •5. Has history of moderate or severe head trauma or other neurological disorder or systemic medical disease that, in the Investigator's opinion, is likely to affect central nervous system functioning. This would include subjects with:
• •1. a current diagnosis of a major neurological disorder;
• •2. seizures, seizure disorder or seizure-like events;
• •3. history of seizure disorder within the immediate family (siblings, parents); or
• •4. encephalopathy
• •Note: Febrile seizures are not exclusionary and will be assessed on a case-by-case basis. If for any reason the subject received medication for a febrile seizure or has a history of complex febrile seizures, this will be exclusionary.
• •6. Has current diagnosis or history of major psychiatric disorders or intellectual disabilities other than ADHD per DSM-5 criteria (including schizophrenia, schizoaffective disorder, bipolar disorder, borderline personality disorder, antisocial personality disorder, narcissistic personality disorder, post-traumatic stress disorder, obsessive-compulsive disorder, severe oppositional defiant disorder (ODD), conduct disorder, and disruptive mood dysregulation disorder, and autism spectrum disorders). The following is not exclusionary:
• •1. a history of mild social anxiety disorder or generalized anxiety disorder according to DSM-5 criteria;
• •2. a history of mild to moderate ODD according to DSM-5 criteria;
• •3. a history of Major Depressive Disorder, if he/she has not experienced a major depressive disorder episode or required psychiatric counselling; or pharmacotherapy within the 6 months prior to screening
• •7. Has a known history of physical, sexual, or emotional abuse in the last year prior to screening.
• •8. Has any other disorder for which its treatment takes priority over treatment of ADHD or is likely to interfere with study treatment, impair treatment compliance, or interfere with interpretation of study results.
• •9. Has a current diagnosis of drug abuse or dependence disorder within the 12 months prior to screening, has a history of drug abuse or dependence disorder or has an immediate family member living at study participant's' home who has current diagnosis drug abuse or dependence disorder (per DSM-5 criteria).
• •10. Evidence of suicidality (defined as either active suicidal plan/intent or active suicidal thoughts, or more than one lifetime suicide attempt) within the six months before Screening or at Screening.
• •11. Has positive findings on C-SSRS for suicidal ideation or behaviors at screening. Has attempted suicide within the 6 months prior to screening, or is at significant risk of suicide, either in the opinion of the Investigator or defined as a "yes" to suicidal ideation questions 4 or 5 or answering "yes" to suicidal behavior on the C-SSRS within the 6 months prior to screening.
• •12. Is currently using, or has a positive result on the urine drug screening for, drugs of abuse (alcohol, amphetamine, barbiturates, benzodiazepines, cannabis \[THC\], cocaine, cotinine, methadone, methamphetamine \[including ecstasy\], methylphenidate, phencyclidine, propoxyphene, and opiates) with the exception of the psychostimulant prescribed for the treatment of ADHD.
• •13. Is unable to discontinue all prohibited medication at least 7 days prior to baseline.
• •14. Has body mass index (BMI) greater than 95th percentile for her/his appropriate age and gender (per CDC's gender specific "BMI-for-age percentiles" charts).
• •15. Has a current diagnosis of significant systemic disease.
• •16. Has uncontrolled thyroid disorder defined as thyroid stimulating hormone ≤ 0.8 x the lower limit of normal or ≥ 1.25 x the upper limit of normal for the reference laboratory range.
• •17. Has resting (sitting) blood pressure and pulse rate greater than the 95th percentile for age and gender.
• •18. Has a known personal history, or presence, of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (e.g., clinically significant heart block or QT interval prolongation: QTc \>0.44 seconds), exercise-related cardiac events including syncope and pre-syncope, or clinically significant bradycardia.
• •19. Has any clinically significant abnormal clinical laboratory test, urine test, electrocardiogram (ECG) result, vital signs or physical examination finding at screening that, in the opinion of the Investigator, would interfere with the safety of the subject
• •20. Has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments.
• •21. Has or has had one or more medical conditions considered clinically significant/relevant by the Investigator in the context of the study (e.g., cardiovascular disease, congestive heart failure, cardiac hypertrophy, arrhythmia, bradycardia \[pulse \< 70 bpm (6-11 years), pulse \< 60 bpm (12-17 years)\], tachycardia \[pulse \> 120 bpm (6-11 years); pulse \> 100 bpm (12-17 years)\], respiratory disease, hepatic impairment or renal insufficiency, metabolic disorder, endocrine disorder, gastrointestinal disorder, hematological disorder, infectious disorder, any clinically significant immunological condition, dermatological disorder.
• •22. Has any disease or medication that could, in the Investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with study conduct or interpretation of results.
• •23. Lost or donated more than 450 mL of blood during the 30 days prior to screening.
• •24. Use of any investigational drug or prohibited concomitant medications including known CYP1A2 substrates (e.g., theophylline, melatonin) within 28 days or 5 half-lives prior to Baseline Visit (Day 1) (whichever is longer) or anticipated for the duration of the study.
• •25. History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations or near drowning with hospital admission.
• •26. Has an allergy to applesauce and cannot swallow capsules whole.
• •27. In the Investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.