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

Inclusion Criteria:

1. Is male or female, 6 to ≤17 years and 9 months of age at screening.
2. Parent(s)/legal guardian(s) is able to read and understand the Informed Consent Form (ICF).
3. Written informed consent obtained by parent(s)/legal guardian(s) and informed assentobtained from the subject, if applicable.
4. Subject and parent(s)/legal guardian(s) are willing and able to comply with all of theprocedures and requirements defined in the protocol, including parents(s)/legalguardian(s) oversight of morning and evening dosing of the SPN-812 and recording adaily medication/dosing diary for psychostimulant and/or SPN-812 during the study.
5. Has lived with the same parent(s)/legal guardian(s) at same residence for at least thelast 6 months prior to screening.
6. Has a primary diagnosis of ADHD (inattentive, hyperactive, or combined presentation)confirmed with the Mini International Neuropsychiatric Interview for Children andAdolescents (MINI-KID) at screening.
7. Is currently on a single, stable psychostimulant regimen (see Inclusion Criterion 8for definition) for treatment of ADHD with a partial, but inadequate efficacy responseto at least 2 weeks of treatment with a psychostimulant (methylphenidate oramphetamine) prior to screening. An inadequate response is defined as aninvestigator-rated ADHD-RS-5 Total score ≥24 and a CGI-S score ≥3 (mildly ill orworse) at Screening and Baseline. Subjects taking additional medication for ADHD (e.g., nonstimulant) are excluded.
8. Is currently and expecting to continue and remain on a stable psychostimulant regimenthroughout the study. A stable stimulant regimen is defined as taking dose at least 5days per week (morning), no significant change in dose or dosing frequency at least 2weeks prior to baseline (Visit 2), and the investigator believes the subject'spsychostimulant dose is optimized.
9. Is functioning at an age-appropriate level intellectually, as judged by theInvestigator.
10. Is a child (6-11 years of age) with a body weight of at least 20 kg at screening or isan adolescent (12-17 years of age) with a body weight of at least 35 kg at screening.
11. Has a resting (sitting) blood pressure (BP) and resting pulse rate measurement withinthe 95th percentile for age, sex, and height.
12. Is considered medically healthy by the Investigator via assessment of physicalexamination, medical and psychiatric histories, clinical laboratory tests, vitalsigns, and electrocardiogram (ECG).
13. Females of childbearing potential (FOCP) must be either sexually inactive (abstinent)or, if sexually active, must agree to use/practice one of the following acceptable,highly effective contraceptive methods beginning/during the screening period prior tothe first dose of SM and throughout the study:
14. Simultaneous use of male condom and intra-uterine contraceptive device placedduring screening period prior to first dose of SM
15. Surgically sterile male partner (e.g., vasectomized partner is sole partner)
16. Barrier method: condom with spermicidal foam/gel/film/cream/suppository orocclusive cap (diaphragm or cervical/vault caps) with spermicidalfoam/gel/film/cream/suppository
17. Established use of oral, injected, or implanted hormonal methods of contraception With approval by the Investigator, subjects' parents or legal guardians may selectabstinence as a form of birth control if deemed more appropriate. For the purposes ofthis study, all females are considered to be of childbearing potential unless they areconfirmed by the Investigator to be premenarchal, biologically sterile, or surgicallysterile (e.g., hysterectomy with bilateral oophorectomy, tubal ligation).
18. Adolescent males, if sexually active, must:
19. Use 2 methods of contraception in combination if his female partner is ofchildbearing potential; this combination of contraceptive methods must be usedfrom the Baseline Visit to ≥ 1 month after the last dose of SM, or
20. Have been surgically sterilized prior to the Screening Visit.

Exclusion Criteria:

1. Is currently participating in another clinical trial or has participated in a clinicaltrial 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 agreeingto use one of the acceptable contraceptive methods throughout the study.
4. Has history of severe drug allergy or hypersensitivity, or known hypersensitivity, tothe study medication (SPN-812).
5. Has history of moderate or severe head trauma or other neurological disorder orsystemic medical disease that, in the Investigator's opinion, is likely to affectcentral nervous system functioning. This would include subjects with:
6. a current diagnosis of a major neurological disorder;
7. seizures, seizure disorder or seizure-like events;
8. history of seizure disorder within the immediate family (siblings, parents); or
9. encephalopathy Note: Febrile seizures are not exclusionary and will be assessed on a case-by-casebasis. If for any reason the subject received medication for a febrile seizure or hasa history of complex febrile seizures, this will be exclusionary.
10. Has current diagnosis or history of major psychiatric disorders or intellectualdisabilities other than ADHD per DSM-5 criteria (including schizophrenia,schizoaffective disorder, bipolar disorder, borderline personality disorder,antisocial personality disorder, narcissistic personality disorder, post-traumaticstress disorder, obsessive-compulsive disorder, severe oppositional defiant disorder (ODD), conduct disorder, and disruptive mood dysregulation disorder, and autismspectrum disorders). The following is not exclusionary:
11. a history of mild social anxiety disorder or generalized anxiety disorderaccording to DSM-5 criteria;
12. a history of mild to moderate ODD according to DSM-5 criteria;
13. a history of Major Depressive Disorder, if he/she has not experienced a majordepressive disorder episode or required psychiatric counselling; orpharmacotherapy within the 6 months prior to screening
14. Has a known history of physical, sexual, or emotional abuse in the last year prior toscreening.
15. Has any other disorder for which its treatment takes priority over treatment of ADHDor is likely to interfere with study treatment, impair treatment compliance, orinterfere with interpretation of study results.
16. Has a current diagnosis of drug abuse or dependence disorder within the 12 monthsprior to screening, has a history of drug abuse or dependence disorder or has animmediate family member living at study participant's' home who has current diagnosisdrug abuse or dependence disorder (per DSM-5 criteria).
17. Evidence of suicidality (defined as either active suicidal plan/intent or activesuicidal thoughts, or more than one lifetime suicide attempt) within the six monthsbefore Screening or at Screening.
18. Has positive findings on C-SSRS for suicidal ideation or behaviors at screening. Hasattempted suicide within the 6 months prior to screening, or is at significant risk ofsuicide, either in the opinion of the Investigator or defined as a "yes" to suicidalideation questions 4 or 5 or answering "yes" to suicidal behavior on the C-SSRS withinthe 6 months prior to screening.
19. Is currently using, or has a positive result on the urine drug screening for, drugs ofabuse (alcohol, amphetamine, barbiturates, benzodiazepines, cannabis [THC], cocaine,cotinine, methadone, methamphetamine [including ecstasy], methylphenidate,phencyclidine, propoxyphene, and opiates) with the exception of the psychostimulantprescribed for the treatment of ADHD.
20. Is unable to discontinue all prohibited medication at least 7 days prior to baseline.
21. Has body mass index (BMI) greater than 95th percentile for her/his appropriate age andgender (per CDC's gender specific "BMI-for-age percentiles" charts).
22. Has a current diagnosis of significant systemic disease.
23. Has uncontrolled thyroid disorder defined as thyroid stimulating hormone ≤ 0.8 x thelower limit of normal or ≥ 1.25 x the upper limit of normal for the referencelaboratory range.
24. Has resting (sitting) blood pressure and pulse rate greater than the 95th percentilefor age and gender.
25. 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 heartblock or QT interval prolongation: QTc >0.44 seconds), exercise-related cardiac eventsincluding syncope and pre-syncope, or clinically significant bradycardia.
26. Has any clinically significant abnormal clinical laboratory test, urine test,electrocardiogram (ECG) result, vital signs or physical examination finding atscreening that, in the opinion of the Investigator, would interfere with the safety ofthe subject
27. Has a concurrent chronic or acute illness (such as severe allergic rhinitis or aninfectious process requiring antibiotics), disability, or other condition that mightconfound the results of safety assessments.
28. Has or has had one or more medical conditions considered clinicallysignificant/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 clinicallysignificant immunological condition, dermatological disorder.
29. Has any disease or medication that could, in the Investigator's opinion, interferewith the assessments of safety, tolerability, or efficacy, or interfere with studyconduct or interpretation of results.
30. Lost or donated more than 450 mL of blood during the 30 days prior to screening.
31. Use of any investigational drug or prohibited concomitant medications including knownCYP1A2 substrates (e.g., theophylline, melatonin) within 28 days or 5 half-lives priorto Baseline Visit (Day 1) (whichever is longer) or anticipated for the duration of thestudy.
32. History of unexplained loss of consciousness, unexplained syncope, unexplainedirregular heartbeats or palpitations or near drowning with hospital admission.
33. Has an allergy to applesauce and cannot swallow capsules whole.
34. In the Investigator's opinion, is unlikely to comply with the protocol or isunsuitable for any other reason.