Dasotraline Pediatric ADHD Study

Inclusion Criteria:

• Subject's parent/legal guardian must give written informed consent, including privacyauthorization, prior to study participation. The subject will complete an informedassent prior to study participation.
• Subject and the subject's parent/legal guardian must be judged by the investigator tobe willing and able to comply with the study procedures and visit schedules.
• Subject, male or female, must be between 6 and 12 years of age, inclusive, at the timeof consent/assent and at Baseline.
• Subject meets Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM

5. criteria for a primary diagnosis of ADHD (inattentive, hyperactive, or combinedpresentation) at screening established by a comprehensive psychiatric evaluation thatreviews DSM 5 criteria is confirmed using the K-SADS-PL at Screening.

• Subject has an ADHD RS IV HV score of ≥ 28.
• Subject has a CGI S score of ≥ 4.
• Subject, if female, must not be pregnant or breastfeeding, and if ≥ 8 years of agemust have a negative pregnancy test.
• Female subject:
• must be unable to become pregnant (eg, premenarchal, surgically sterile, etc); OR

• practice true abstinence (consistent with lifestyle) and must agree to remain abstinentfrom signing informed consent/assent to at least 14 days after the last dose of study drughas been taken; OR

• is sexually active and willing to use a medically effective method of birth control (seeAppendix VII) from signing informed consent/assent to at least 14 days after the last doseof study drug has been taken.

• Male subject must be willing to remain sexually abstinent (consistent with lifestyle)or be using an effective method of birth control from signing informed consent/assentto at least 14 days after the last dose of study drug has been taken.
• Subject must be in general good health (defined as the absence of any clinicallyrelevant abnormalities as determined by the Investigator) based on screening physicaland neurological examinations, vital signs, medical history, and clinical laboratoryvalues (hematology, chemistry, and urinalysis). Note: If any of the hematology,chemistry, or urinalysis results are not within the laboratory's reference range, thenthe subject may be included only if the investigator determines the deviations to benot clinically relevant.
• Subject weighs at least 21 kg and is within 3rd to 97th percentile for gender specificbody-mass-index (BMI)-for-age from the World Health Organization (WHO) growth charts (see Appendices II and IX).
• Subject's parent/legal guardian must report a history of the subject being able toswallow capsules.
• Subject and subject's parents/legal guardians must be able to fully comprehend theinformed consent/assent form (as applicable), understand all study procedures, and beable to communicate satisfactorily with the Investigator and study coordinator.

Exclusion Criteria:

• Subject or parent/legal guardian has commitments during the study that would interferewith attending study visits.
• Subject currently has a diagnosis of asthma that has required daily treatment withbronchodilators or nebulizer treatments in the 30 days prior to screening and/or whomay require daily treatments with these agents over the course of the trial.Intermittent use of bronchodilators is not exclusionary. Subjects who have a historyof requiring persistent asthma treatment should be discussed wit the medical monitorprior to enrolment.
• 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 ofa condition (eg, malabsorption, gastrointestinal surgery) that may interfere with drugabsorption, distribution, metabolism, or excretion. Note: Active medical conditionsthat are minor or well-controlled are not exclusionary if they do not affect risk tothe subject or the study results. In cases in which the impact of the condition uponrisk to the subject or study results is unclear, the Medical Monitor should beconsulted. Any subject with a known cardiovascular disease or condition (even ifcontrolled) must be discussed with the Medical Monitor during screening.
• Subject has a history or presence of abnormal ECGs, which in the investigator'sopinion is clinically significant. Screening site ECGs will be centrally over-read,and eligibility will be determined by the investigator based on the results of theover-read report.
• Subject has any documented diagnosis of Bipolar I or II Disorder, major depressivedisorder, conduct disorder, obsessive-compulsive disorder, disruptive mooddysregulation disorder (DMDD), intellectual disability, any history of psychosis,autism spectrum disorder, Tourette's Syndrome, confirmed genetic disorder withcognitive and/or behavioral disturbances. Note: Subjects with oppositional defiantdisorder (ODD) are permitted to enroll in the study as long as ODD is not the primaryfocus of treatment.
• Subject has generalized anxiety disorder that has been the primary focus of treatmentat any time during the 12 months prior to screening or that required pharmacotherapyany time in the 6 months prior to screening.
• Subject has failed 2 adequate courses of stimulant or non-stimulant treatment forADHD, as judged by the investigator.
• Subject has evidence of any chronic disease of the central nervous system (CNS) suchas tumors, inflammation, seizure disorder, vascular disorder, potential CNS relateddisorders that might occur in childhood (eg, Duchenne Muscular dystrophy, myastheniagravis, or other neurologic or serious neuromuscular disorders), or history ofpersistent neurological symptoms attributable to serious head injury. Past history offebrile seizure, drug-induced seizure, or alcohol withdrawal seizure is exclusionary.Subject taking anticonvulsants for seizure control currently or within the past 2years is not eligible for study participation.
• Subject has uncontrolled thyroid disorder indicated by free T4, free T3, or thyroidstimulating hormone (TSH) outside the limit of normal for the reference laboratory.
• Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation withsome intent to act, without specific plan) or item 5 (active suicidal ideation withspecific plan and intent) for any lifetime history on the C SSRS Children'sLifetime/Recent assessment at screening.
• Subject has any history of attempted suicide, in the opinion of the investigator.
• Subject does not tolerate venipuncture or has poor venous access that would causedifficulty for collecting blood samples.
• Subject has a history of severe allergies to more than 1 class of medications ormultiple adverse drug reactions or has a history of allergic reaction or has a knownor suspected sensitivity to any substance that is contained in the study drugformulations.
• Subject has history of intolerance to stimulants.
• Subject has taken any antipsychotic medication within 8 weeks prior to screening.
• Subject taking any medication, including health food supplements with purportedpsychotropic activity (for example, St. John's Wort), must have a minimum washout of 7days prior to Day 1.
• Subject taking any antidepressant medication (eg, bupropion, selective serotoninreuptake inhibitor [SSRI]/ serotonin norepinephrine reuptake inhibitor [SNRI],monoamine oxidase [MAO] inhibitor, tricyclic, etc) must have a minimum washout of 7days prior to Day 1.
• Subject is currently undergoing Cognitive Behavioral Therapy (CBT) for the treatmentof ADHD, has initiated behavioral therapy (including school based interventions) lessthan 1 month prior to screening, or is receiving behavioral therapy and in the opinionof the investigator will not be able to follow a stable routine for the duration ofthe study.
• Subject or subject's family anticipates a move outside the geographic range ofinvestigative site during the study period, or plans extended travel inconsistent withthe recommended visit interval during study duration.
• Subject has a history of, or current malignancy except for non melanomatous skincancer.
• Subject has history of positive test for Hepatitis B surface antigen or Hepatitis Cantibody and has liver function test results at screening above the upper limit ofnormal for the reference laboratory.
• Subject is known to have tested positive for human immunodeficiency virus (HIV).
• Subject has participated in any investigational study within 90 days prior toscreening or is currently participating in another clinical trial.
• Subject has a history of substance or alcohol use disorder (excluding caffeine) withinthe 12 months prior to screening, as defined by the DSM 5 criteria, or is currentlyusing tobacco or other nicotine-containing products, or has a positive urine drugscreen (UDS) or breath alcohol test at screening. Note: Subjects with a positive UDSmay be allowed to continue in the study, provided that the investigator determinesthat the positive test is as a result of taking prescription medicine(s) asprescribed.
• Subject requires treatment with any disallowed medications during the study.
• Subject has experienced significant blood loss within 60 days prior to screening.
• Subject has previously been enrolled in a clinical trial of dasotraline (SEP 225289).
• Subject's parent/legal guardian is an investigational site staff member or therelative of an investigational site staff member.
• Subject is, in the opinion of the Investigator, unsuitable in any other way toparticipate in this study.