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.
Condition: Attention-Deficit Hyperactivity Disorder (ADHD)
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: dasotraline; Placebo
Intervention description: dasotraline 2mg capsule once daily; Placebo capsule once daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study in children with ADHD in a laboratory classroom setting
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double Blind
Enrollment: 95.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Attention-Deficit Hyperactivity Disorder (ADHD)

Summary:

      A study to evaluate the efficacy and safety of dasotraline in children 6 to 12 years of age
      with Attention-Deficit Hyperactivity Disorder (ADHD) in a simulated classroom setting.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is 6 - 12 years old, inclusive at screening and randomization.

          2. Subject weighs ≤ 30 kg at the time of screening.

          3. At least one of the subject's parents/legal guardians must give written informed
             consent, including privacy authorization, prior to study participation. The subject
             will provide informed assent prior to study participation.

          4. Subject meets Diagnostic and Statistical Manual of Mental Disorders Fifth Edition
             (DSM-5) criteria for a primary diagnosis of ADHD (inattentive, hyperactive, or
             combined presentation) at screening established by a comprehensive psychiatric
             evaluation that reviews DSM-5 criteria and confirmed using the Schedule for Affective
             Disorders and Schizophrenia for School-Age Children-Present and Lifetime version
             (K-SADS-PL) at screening.

          5. Subject is currently either untreated for ADHD or receiving a treatment regimen of a
             stimulant medication prescribed as monotherapy (i.e., methylphenidate, mixed
             amphetamine salts, lisdexamphetamine, or dextroamphetamine) within the approved
             labeled dose range for ADHD..

          6. In the opinion of the investigator, the subject is not treatment refractory.

          7. Any subject not receiving ADHD medication at screening must display clinically
             significant ADHD symptoms, as measured by an ADHD-RS-IV score ≥ 26 at screening and
             Day -7.

          8. For any subject receiving monotherapy stimulant treatment for ADHD, that treatment
             must be well tolerated and clinically effective based on clinical assessment and
             informant interview, as well as, review of available medical records. Note: The ADHD
             Rating Scale Version IV - Home Version (modified for investigator administration)
             (ADHD RS IV HV) will be administered at Screening by the investigator to inform
             clinical evaluation.

          9. Subject is male or a non-pregnant, non-lactating female.

         10. Subject, if female, must not be pregnant or breastfeeding, and if ≥ 8 years of age
             must have a negative serum pregnancy test at screening.

         11. Female subjects of childbearing potential and male subjects with female partners of
             childbearing potential must practice true abstinence (consistent with lifestyle) and
             must agree to remain abstinent or agree to use an effective and medically acceptable
             form of birth control, from the time of informed consent/assent to at least 14 days
             after the last dose of the study drug has been taken.

         12. Subject must be in general good health (defined as the absence of any clinically
             relevant abnormalities as determined by the investigator) based on screening physical
             and neurological examinations, medical history, and clinical laboratory values
             (hematology, chemistry, and urinalysis). Note: If any of the hematology, chemistry, or
             urinalysis results are not within the laboratory's reference range, then the subject
             can be included only if the investigator determines the deviations to be not
             clinically relevant.

         13. Subject is within the 3rd to 97th percentile for gender specific weight-for-age from
             the Centers for Disease Control and Prevention (CDC) growth charts

         14. Subject must report a history of being able to swallow capsules.

         15. Subject and subject's parent/legal guardian must be able to fully comprehend the
             informed consent/assent forms, understand and be willing and able to comply with all
             study procedures and visit schedule, and be able to communicate satisfactorily with
             the investigator and study coordinator.

         16. Subject, on Day -1, has evidence of clinically significant ADHD symptoms as measured
             by an ADHD RS IV HV total score ≥ 26. If subject has been receiving stimulant
             pharmacotherapy for ADHD the ADHD RS-IV should be administered following a minimum 72
             hour washout from prior ADHD medication treatment.

        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.

         14. Subjects taking anticonvulsants for seizure control currently or within the past 2
             years are not eligible for study participation.

         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.