Dasotraline SEP360-105 Pediatric PK/PD Study

To characterize the pharmacokinetics (PK) and assess safety and tolerability of a range of
single oral doses of SEP-225289 in subjects 6 to 17 years old with ADHD

Inclusion Criteria:

Subject, male or female, must be between 6 and 17 years of age, inclusive, at the time of
consent. Note: Subjects who are 17 years of age at time of consent must not have a
birthday within the following 4 weeks in order to be eligible for the study.

- Subject meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition;
Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD (inattentive,
hyperactive, or combined subtype) established by a comprehensive psychiatric
evaluation that reviews DSM-IV-TR criteria prior to Screening. Diagnosis is confirmed
at Screening using Mini International Neuropsychiatric Interview for Children and
Adolescents (MINI-KID).

- Subject's parents/legal guardians must give written informed consent, including
privacy authorization, prior to study participation. The subject will complete an
informed assent prior to study participation. Note: Informed consent will be obtained
from both parents unless one parent is deceased, unknown, incompetent, or when one
parent has legal responsibility for the care and custody of the child.

- Subject and the subject's parents/legal guardians must be judged by the investigator
to be willing and able to comply with the study procedures and visit schedules,
including venipuncture, overnight stay (recommended for parent/legal guardian to
remain overnight with the subject), and follow-up visits.

- Subject, if female, must not be pregnant or breastfeeding, and if ≥ 8 years of age
must have a negative serum pregnancy test at screening.

- Female subjects of childbearing potential and male subjects with female partners of
childbearing potential must agree to use an effective and medically acceptable form
of birth control throughout the study period.

- 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.

- Subject is within 3rd to 97th percentile for gender specific body mass index
(BMI)-for-age from the World Health Organization (WHO) growth charts (Appendix VI)
and weighs at least 25 kg.

- Subject must report a history of being able to swallow capsules.

- Subject and subject's parents/legal guardians must be able to fully comprehend the
informed consent/assent form, understand all study procedures, and be able to
communicate satisfactorily with the investigator and study coordinator.

Exclusion Criteria:

Subject or parents/legal guardians have daily commitments during the study that would
interfere with attending study visits.

- 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.

- Subject has a history or presence of abnormal ECGs, which in the investigator's
opinion is clinically significant. Screening ECGs will be centrally over-read, and
eligibility will be determined based on the over-read report.

- Subject has a documented history of Bipolar I or II Disorder, major depression,
conduct disorder, oppositional defiant disorder, generalized anxiety disorder (other
than obsessive-compulsive disorder) or any history of psychosis, that has been the
primary focus of treatment at any time during the 12 months prior to screening.

- Subject has organic brain disease, for example, traumatic brain injury residua, or a
history of febrile seizures. Subjects taking anticonvulsants for seizure control
currently or within the past 2 years are not eligible for study participation.

- 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) on the C-SSRS Children's Lifetime/Recent assessment at
screening. Subjects who have significant findings for suicidal ideation upon
completion of the C-SSRS must be referred to the investigator for follow-up
evaluation.

- Subject has any history of attempted suicide.

- Subject does not tolerate venipuncture or has poor venous access that would cause
difficulty for collecting blood samples.

- Subject has a history of severe allergies to more than 1 class of medications or
multiple adverse drug reactions.

- Subject has history of exposure to stimulants with intolerable side effects.

- Subject has taken any antipsychotic medication within 8 weeks of Visit 1 (Screening).

- Subject is taking any psychotropic medication, including health-food supplements with
purported central nervous system activity (eg, St. John's Wort, melatonin), must have
a washout equal to a minimum of 5 half lives of that medication prior to Visit 2. If
the half life of a medication is unknown, for example, herbal products, then the
subject should have a 28 day medication washout.

- Subject is currently taking an antidepressant medication (eg, bupropion, selective
serotonin reuptake inhibitor [SSRI]/ serotonin norepinephrine reuptake inhibitor
[SNRI], monoamine oxidase [MAO] blocker, tricyclic, etc).

- Subject or subject's family anticipates a move outside the geographic range of the
investigative site during the study period, or plans extended travel inconsistent
with the recommended visit interval during study duration.

- Subject has a history of, or current malignancy except for non melanoma skin cancer.

- Subject has a positive screening test for Hepatitis B surface antigen, Hepatitis C
antibody, or human immunodeficiency virus (HIV)-1 or HIV-2.

- Subject has participated in any investigational study within 30 days prior to
screening or is currently participating in another clinical trial.

- Subject has a history of substance abuse or drug dependence (excluding nicotine and
caffeine) within the 12 months prior to screening, as defined by the DSM IV TR
criteria or has a positive urine drug screen (UDS), cotinine test, or breath alcohol
test at Visit 1.

- Subject is taking any disallowed medications for chronic treatment.

- Subject has experienced significant blood loss within 60 days or has donated plasma
within 72 hours prior to Visit 1 or intends to donate blood or undergo elective
surgery within 30 days following Visit 2.

- Subject has a history of allergic reaction or has a known or suspected sensitivity to
any substance that is contained in the study drug formulation.

- Subject is a relative of an investigational site staff member.

- Subject is, in the opinion of the investigator, unsuitable in any other way to
participate in this study.