A Study to Evaluate the Efficacy and Safety of Dasotraline in Children 6 to 12 Years Old With Attention-Deficit Hyperactivity Disorder (ADHD) in a Simulated Classroom Setting.

Exclusion Criteria

• •1. Subject or parent/legal guardian has commitments during the study that would interfere with attending study visits.
• •2. Subject is currently being treated for ADHD with a non-stimulant product, or has been treated with a non-stimulant product in the 4 weeks prior to the start of screening.
• •3. Subject has failed 2 adequate courses (dose and duration) of stimulant or non-stimulant treatment for ADHD.
• •4. Subject is considered treatment refractory, as judged by the investigator.
• •5. Subject currently has a diagnosis of asthma that has required daily treatment with bronchodilators or nebulizer treatments in the 30 days prior to screening and/or who may require daily treatments with these agents over the course of the trial. Intermittent use of bronchodilators is not exclusionary. Subjects who have a history of requiring persistent asthma treatment should be discussed with the medical monitor prior to randomization.
• •6. Subject has any clinically significant unstable medical abnormality, chronic disease, or a history of a clinically significant abnormality of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems, or a disorder or history of a condition (eg, malabsorption, gastrointestinal surgery) that may interfere with drug absorption, distribution, metabolism, or excretion. Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the medical monitor should be consulted. Any subject with a known cardiovascular disease or condition (even if controlled) must be discussed with the medical monitor during screening.
• •7. Subject has a history or presence of abnormal ECGs, which in the investigator's opinion is clinically significant. Screening site ECGs will be centrally over-read, and eligibility will be determined by the investigator based on the results of the over-read report.
• •8. Subject has any diagnosis of bipolar I or II disorder, major depressive disorder, conduct disorder, obsessive-compulsive disorder, any history of psychosis, autism spectrum disorder, disruptive mood dysregulation disorder (DMDD), intellectual disability, Tourette's Syndrome, confirmed genetic disorder with cognitive and/or behavioral disturbances. Note: Subjects with oppositional defiant disorder (ODD) are permitted to enroll in the study as long as ODD is not the primary focus of treatment.
• •9. Subject has a first-degree relative (biological parent or sibling) with a history of schizophrenia, schizoaffective disorder, bipolar I disorder, or bipolar II disorder.
• •10. Subject has generalized anxiety disorder or panic disorder that has been the primary focus of treatment at any time during the 12 months prior to screening or that has required pharmacotherapy any time during the 6 months prior to screening.
• •11. Subject has evidence of any chronic disease of the central nervous system (CNS) such as tumors, inflammation, seizure disorder, vascular disorder, potential CNS related disorders that might occur in childhood (eg, Duchenne Muscular dystrophy, myasthenia gravis, or other neurologic or serious neuromuscular disorders)
• •12. Subjects with a history of persistent neurological symptoms attributable to serious head injury.
• •13. History of febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is exclusionary.
• •15. Subject has uncontrolled thyroid disorder as evidenced by thyroid stimulating hormone (TSH) ≤ 0.8 x the lower limit of normal (LLN) or ≥ 1.25 x the upper limit of normal (ULN) for the reference laboratory
• •16. Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) for any lifetime history on the C-SSRS Children's Lifetime/Recent assessment at screening.
• •17. Subject has any history of attempted suicide or clinically significant suicidal ideation, in the opinion of the investigator.
• •18. Subject has a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions or has a history of allergic reaction or has a known or suspected sensitivity to any substance that is contained in the study drug formulations
• •19. Subject has history of intolerance (safety) or lack of efficacy to stimulants.
• •20. Subject has taken any antipsychotic medication within 6 months prior to screening.
• •21. Subject has taken any herbal and/or complementary treatments, eg, St. John's Wort, within 6 months prior to Day 1.
• •22. Subject has taken any antidepressant medication (eg, bupropion, selective serotonin reuptake inhibitor \[SSRI\]/ serotonin norepinephrine reuptake inhibitor \[SNRI\], tricyclic, etc) within 6 months prior to Day 1.
• •23. Subject has ever taken any monoamine oxidase \[MAO\] inhibitor at any time.
• •24. Subject is currently undergoing ongoing or newly initiated Cognitive Behavioral Therapy (CBT) for the treatment of ADHD; behavioral therapies, including school based interventions that were initiated less than one month prior to screening; or, behavioral therapy that in the opinion of the investigator would interfere with the subject's ability to participate for the duration of the study. School based interventions that have been in place for more than one month prior to screening will be allowed. Note: Unavoidable changes in school-based interventions that occur during study participation will not be exclusionary, but should be documented by the investigator, to the extent possible. Subjects should not be enrolled who, in the judgment of the investigator, are expected to start substantially different or more intensive course of behavioral therapy over the duration of their participation in the study.
• •25. Subject or subject's family anticipates a move outside the geographic range of investigative site during the study period, or plans extended travel inconsistent with the recommended visit interval during study duration.
• •26. Subject has history of, or current, malignancy other than non-melanomatous skin cancer.
• •27. Subject has history of positive test for Hepatitis B surface antigen or Hepatitis C antibody.
• •28. Subject is known to have tested positive for human immunodeficiency virus (HIV).
• •29. Subject has participated in a classroom study within 6 months prior to the start of screening or has participated in any other clinical study with an investigational drug/product within 90 days prior to the start of screening or is currently participating in another clinical trial.
• •30. Subject shows evidence of substance or alcohol use or is currently using tobacco or other nicotine-containing products, or has a positive urine drug screen (UDS) at screening. Note: Subjects with a positive UDS may be allowed to continue in the study, provided that the investigator determines that the positive test is as a result of taking medications as prescribed after consultation with the medical monitor.
• •31. Subject is taking any disallowed medications for chronic treatment.
• •32. Subject has previously been enrolled in a clinical trial of dasotraline (SEP-225289).
• •33. Subject's parent/legal guardian is an investigational site staff member or the relative of an investigational site staff member.
• •34. Subject is, in the opinion of the investigator, unsuitable in any other way to participate in this study.
• •35. Subject's sibling or family member living in the same household is participating in the same laboratory classroom cohort for this study.
• •36. Subject is unable to perform at the basic level of the standardized math test as defined in the laboratory classroom manual.