Adult Attention Deficit Hyperactivity Disorder
Condition: Adult Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: SEP-225289; SEP-225289; Placebo
Intervention description: SEP-225289 4mg once daily; SEP-225289 8mg once daily; Placebo once daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 341.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: ADHD; Attention deficit hyperactivity disorder

Summary:

      A Phase 2 study of SEP-225289 in adults with attention deficit hyperactivity disorder (ADHD).
    

Eligibility criteria:

        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.