Adult Attention Deficit Hyperactivity Disorder

This is a Phase 2, randomized, double-blind, parallel-group, multicenter, outpatient study
evaluating the efficacy and safety of SEP 225289 in adults with ADHD using 2 oral dosages (4
or 8 mg SEP 225289 once daily [QD]) versus placebo over a 4 week treatment period.

Inclusion Criteria:

- 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. Diagnosis is confirmed by Conners' Adult
ADHD Diagnostic Interview (CAADID) Part 2.

- Subject currently taking medication (stimulant or nonstimulant) for the control of
ADHD symptoms has an ADHD RS-IV score of ≥ 22 at screening.

- Subject currently not taking any medication for the purpose of controlling ADHD
symptoms has an ADHD RS-IV score of ≥ 26 at screening.

- Subject has a CGI-S score of ≥ 4 at screening.

- Subject has a lifetime history of treatment with at least one medication for ADHD
(stimulant or nonstimulant). Subjects may be either medicated or unmedicated for ADHD
at the time of screening (all ADHD medications must be washed out during screening).

- Subject has a negative breath alcohol test and a negative urine drug screen (UDS) for
any illicit drug at screening, unless a false positive is suspected, in which case
the UDS will be repeated. If the subject has a positive drug screen for ADHD
medications (ie, methylphenidate or amphetamine) at screening; the subject must have
a negative UDS after a washout period at least 3 days prior to baseline.

- Subject is male or a non-pregnant, non-lactating female.

- Female subjects must have a negative serum pregnancy test at screening; women who are
post-menopausal (defined as at least 12 months of spontaneous amenorrhea) and those
who have undergone hysterectomy or bilateral oophorectomy will be exempted from the
pregnancy test.

- Female subjects of childbearing potential and male subjects with female partners of
child-bearing potential must agree to use an effective and medically acceptable form
of birth control throughout the study period and for one month (30 days) after study
completion. Medically acceptable and effective contraceptives include abstinence,
prescription hormonal contraceptives (oral, patch, vaginal ring, implant, or
injection), diaphragm with spermicide, intrauterine device (IUD), condom with
spermicide, surgical sterilization, or vasectomy. For male subjects adequate
contraception is defined as abstinence or continuous use of 2 barrier methods of
contraception (eg, spermicidal condom).

- Subject is 18 to 55 years old, inclusive, at the time of informed consent. 11.
Subject can read well enough to understand the informed consent form and other
subject materials.

Exclusion Criteria:

- Subject has a DSM-IV-TR diagnosis of ADHD not otherwise specified.

- Subject is receiving adequate benefit from current ADHD medication in the opinion of
the investigator.

- Subject has an Axis I disorder other than ADHD that has been the primary focus of
treatment at any time during the 12 months prior to screening.

- Subject has a past history of, or current presentation consistent with, bipolar
disorder (including bipolar I, bipolar II, and bipolar not otherwise specified
[NOS]), schizophrenia, schizoaffective disorder, or any other psychotic disorder.

- Subject has a history of drug dependence or substance abuse (excluding nicotine and
caffeine) within the 12 months prior to screening, as defined by the DSM-IV-TR
criteria.

- Subject has a current Axis II disorder per DSM-IV-TR criteria.

- Subject has a history of epilepsy, seizures (except childhood febrile seizures),
unexplained syncope or other unexplained blackouts (except single incident), or head
trauma with loss of consciousness lasting more than 5 minutes.

- Subject has a currently active medical condition (other than ADHD) that, in the
opinion of the investigator, could interfere with the ability of the subject to
participate in the study.

- 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) or St. John's Wort.

- Subject is currently taking or has taken within the previous 6 months an
anticonvulsant medication (eg, phenytoin, carbamazepine, lamotrigine, valproic acid,
etc); antipsychotic medication; or lithium (any lithium preparation or formulation).

- Subject is currently taking an alpha-2 adrenergic receptor agonist (including
clonidine and guanfacine).

- Subject has a Body Mass Index (BMI) less than 18 or greater than 35 kg/m2 (refer to
Appendix V)

- 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 assessment at screening (in the past month).
Subjects who answer "yes" to this question must be referred to the Investigator for
follow-up evaluation.

- Subject has attempted suicide within 2 years prior to the screening period.

- Subject has history of positive test for Hepatitis B surface antigen or Hepatitis C
antibody. Note: Subjects with a history of a positive test for Hepatitis B surface
antigen or Hepatitis C antibody may be enrolled in the study if they have liver
function test results at screening within the normal range.

- Subject is known to have tested positive for human immunodeficiency virus (HIV).

- Subject has a clinically significant abnormality on screening evaluation including
physical examination, vital signs, ECG, or laboratory tests that the investigator in
consultation with the medical monitor considers to be inappropriate to allow
participation in the study.

- The subject's screening ECG shows a corrected QT interval using Fridericia's formula
(QTcF) of ≥ 450 msec for male subjects or ≥ 470 msec for female subjects.

- The subject's screening hematology results show an alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) value ≥ 2 times the upper limit of normal (ULN), or
a blood urea nitrogen (BUN) value ≥ 1.5 times the ULN for the reference lab.

- Subject who is currently participating or has participated in a clinical trial within
the last 180 days or who participated in more than 2 clinical trials within the past
year. This includes studies using marketed compounds or devices.

- Subject is at high risk of non-compliance in the investigator's opinion.