<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01692782</url>
  </required_header>
  <id_info>
    <org_study_id>SEP360-201</org_study_id>
    <nct_id>NCT01692782</nct_id>
  </id_info>
  <brief_title>Adult Attention Deficit Hyperactivity Disorder</brief_title>
  <official_title>A Randomized, Double Blind, Parallel Group, Multicenter Efficacy and Safety Study of SEP-225289 Versus Placebo in Adults With Attention Deficit Hyperactivity Disorder (ADHD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sumitomo Pharma America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sumitomo Pharma America, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase 2 study of SEP-225289 in adults with attention deficit hyperactivity disorder (ADHD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, randomized, double-blind, parallel-group, multicenter, outpatient study&#xD;
      evaluating the efficacy and safety of SEP 225289 in adults with ADHD using 2 oral dosages (4&#xD;
      or 8 mg SEP 225289 once daily [QD]) versus placebo over a 4 week treatment period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline at Week 4 in ADHD Symptoms Measured With the ADHD Rating Scale Version IV With Adult Prompts (ADHD RS IV)</measure>
    <time_frame>4 Weeks</time_frame>
    <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in ADHD Symptoms Measured With the ADHD RS IV at Weeks 1, 2, 3.</measure>
    <time_frame>Weeks 1, 2, 3</time_frame>
    <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores (range 0 - 54).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI S) at Weeks 1, 2, 3, 4.</measure>
    <time_frame>Weeks 1, 2, 3, 4</time_frame>
    <description>The CGI-S modified asked the clinician one question: Considering your total clinical experience with adult ADHD, how mentally ill is the subject at this time?&quot;.The clinician's answer was rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = ng the most extremely ill subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Inattentiveness and Hyperactivity Subscales of the ADHD RS IV at Weeks 1, 2, 3, 4</measure>
    <time_frame>Weeks 1, 2, 3, 4</time_frame>
    <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The even number items (2, 4, 6, 8, 10, 12, 14, 16, 18) assess hyperactive impulsive symptoms and the odd number items (1, 3, 5, 7, 9, 11, 13, 15, 17) assess inattentive symptoms. The ADHD inattentiveness subscale score is defined as sum of items (1, 3, 5, 7, 9, 11, 13, 15, 17) scores (range 0 - 27). The ADHD hyperactive impulsive subscale score is defined as sum of items (2, 4, 6, 8, 10, 12, 14, 16, 18) scores (range 0 - 27).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Responders at Weeks 1, 2, 3, 4. A Responder is Defined as a Subject With a ≥ 30% Improvement in ADHD Symptoms Compared With Baseline as Measured by the ADHD RS IV.</measure>
    <time_frame>Weeks 1, 2, 3, 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Wender-Reimher Adult Attention Deficit Disorder Scale (WRAADDS) as Measured at Weeks 1, 2, 3, 4.</measure>
    <time_frame>Weeks 1, 2, 3, 4</time_frame>
    <description>The WRAADDS measured the severity of the target symptoms of adults with ADHD. It measured symptoms in 7 categories: attention difficulties, hyperactivity/restlessness, temper, affective lability, emotional overreactivity, disorganization, and impulsivity. The scale rated individual items from 0 to 2 (0 = not present, 1 = mild, 2 = clearly present) and summarized each of the 7 categories on a 0 to 4 scale (0 = none, 1 = mild, 2 = moderate, 3 = quite a bit, 4 = very much). The WRAADDS total score is defined as sum of all 28 item subscores (range 0 - 56).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">341</enrollment>
  <condition>Adult Attention Deficit Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>SEP-225289 4mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SEP-225289 8mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>4 capsules of placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SEP-225289</intervention_name>
    <description>SEP-225289 4mg once daily</description>
    <arm_group_label>SEP-225289 4mg</arm_group_label>
    <other_name>Dasotraline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SEP-225289</intervention_name>
    <description>SEP-225289 8mg once daily</description>
    <arm_group_label>SEP-225289 8mg</arm_group_label>
    <other_name>Dasotraline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition;&#xD;
             Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD (inattentive,&#xD;
             hyperactive, or combined subtype) established by a comprehensive psychiatric&#xD;
             evaluation that reviews DSM-IV-TR criteria. Diagnosis is confirmed by Conners' Adult&#xD;
             ADHD Diagnostic Interview (CAADID) Part 2.&#xD;
&#xD;
          -  Subject currently taking medication (stimulant or nonstimulant) for the control of&#xD;
             ADHD symptoms has an ADHD RS-IV score of ≥ 22 at screening.&#xD;
&#xD;
          -  Subject currently not taking any medication for the purpose of controlling ADHD&#xD;
             symptoms has an ADHD RS-IV score of ≥ 26 at screening.&#xD;
&#xD;
          -  Subject has a CGI-S score of ≥ 4 at screening.&#xD;
&#xD;
          -  Subject has a lifetime history of treatment with at least one medication for ADHD&#xD;
             (stimulant or nonstimulant). Subjects may be either medicated or unmedicated for ADHD&#xD;
             at the time of screening (all ADHD medications must be washed out during screening).&#xD;
&#xD;
          -  Subject has a negative breath alcohol test and a negative urine drug screen (UDS) for&#xD;
             any illicit drug at screening, unless a false positive is suspected, in which case the&#xD;
             UDS will be repeated. If the subject has a positive drug screen for ADHD medications&#xD;
             (ie, methylphenidate or amphetamine) at screening; the subject must have a negative&#xD;
             UDS after a washout period at least 3 days prior to baseline.&#xD;
&#xD;
          -  Subject is male or a non-pregnant, non-lactating female.&#xD;
&#xD;
          -  Female subjects must have a negative serum pregnancy test at screening; women who are&#xD;
             post-menopausal (defined as at least 12 months of spontaneous amenorrhea) and those&#xD;
             who have undergone hysterectomy or bilateral oophorectomy will be exempted from the&#xD;
             pregnancy test.&#xD;
&#xD;
          -  Female subjects of childbearing potential and male subjects with female partners of&#xD;
             child-bearing potential must agree to use an effective and medically acceptable form&#xD;
             of birth control throughout the study period and for one month (30 days) after study&#xD;
             completion. Medically acceptable and effective contraceptives include abstinence,&#xD;
             prescription hormonal contraceptives (oral, patch, vaginal ring, implant, or&#xD;
             injection), diaphragm with spermicide, intrauterine device (IUD), condom with&#xD;
             spermicide, surgical sterilization, or vasectomy. For male subjects adequate&#xD;
             contraception is defined as abstinence or continuous use of 2 barrier methods of&#xD;
             contraception (eg, spermicidal condom).&#xD;
&#xD;
          -  Subject is 18 to 55 years old, inclusive, at the time of informed consent. 11. Subject&#xD;
             can read well enough to understand the informed consent form and other subject&#xD;
             materials.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has a DSM-IV-TR diagnosis of ADHD not otherwise specified.&#xD;
&#xD;
          -  Subject is receiving adequate benefit from current ADHD medication in the opinion of&#xD;
             the investigator.&#xD;
&#xD;
          -  Subject has an Axis I disorder other than ADHD that has been the primary focus of&#xD;
             treatment at any time during the 12 months prior to screening.&#xD;
&#xD;
          -  Subject has a past history of, or current presentation consistent with, bipolar&#xD;
             disorder (including bipolar I, bipolar II, and bipolar not otherwise specified [NOS]),&#xD;
             schizophrenia, schizoaffective disorder, or any other psychotic disorder.&#xD;
&#xD;
          -  Subject has a history of drug dependence or substance abuse (excluding nicotine and&#xD;
             caffeine) within the 12 months prior to screening, as defined by the DSM-IV-TR&#xD;
             criteria.&#xD;
&#xD;
          -  Subject has a current Axis II disorder per DSM-IV-TR criteria.&#xD;
&#xD;
          -  Subject has a history of epilepsy, seizures (except childhood febrile seizures),&#xD;
             unexplained syncope or other unexplained blackouts (except single incident), or head&#xD;
             trauma with loss of consciousness lasting more than 5 minutes.&#xD;
&#xD;
          -  Subject has a currently active medical condition (other than ADHD) that, in the&#xD;
             opinion of the investigator, could interfere with the ability of the subject to&#xD;
             participate in the study.&#xD;
&#xD;
          -  Subject is currently taking an antidepressant medication (eg, bupropion, selective&#xD;
             serotonin reuptake inhibitor [SSRI]/ serotonin norepinephrine reuptake inhibitor&#xD;
             [SNRI], monoamine oxidase [MAO] blocker, tricyclic, etc) or St. John's Wort.&#xD;
&#xD;
          -  Subject is currently taking or has taken within the previous 6 months an&#xD;
             anticonvulsant medication (eg, phenytoin, carbamazepine, lamotrigine, valproic acid,&#xD;
             etc); antipsychotic medication; or lithium (any lithium preparation or formulation).&#xD;
&#xD;
          -  Subject is currently taking an alpha-2 adrenergic receptor agonist (including&#xD;
             clonidine and guanfacine).&#xD;
&#xD;
          -  Subject has a Body Mass Index (BMI) less than 18 or greater than 35 kg/m2 (refer to&#xD;
             Appendix V)&#xD;
&#xD;
          -  Subject answers &quot;yes&quot; to &quot;Suicidal Ideation&quot; item 4 (active suicidal ideation with&#xD;
             some intent to act, without specific plan) or item 5 (active suicidal ideation with&#xD;
             specific plan and intent) on the C-SSRS assessment at screening (in the past month).&#xD;
             Subjects who answer &quot;yes&quot; to this question must be referred to the Investigator for&#xD;
             follow-up evaluation.&#xD;
&#xD;
          -  Subject has attempted suicide within 2 years prior to the screening period.&#xD;
&#xD;
          -  Subject has history of positive test for Hepatitis B surface antigen or Hepatitis C&#xD;
             antibody. Note: Subjects with a history of a positive test for Hepatitis B surface&#xD;
             antigen or Hepatitis C antibody may be enrolled in the study if they have liver&#xD;
             function test results at screening within the normal range.&#xD;
&#xD;
          -  Subject is known to have tested positive for human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Subject has a clinically significant abnormality on screening evaluation including&#xD;
             physical examination, vital signs, ECG, or laboratory tests that the investigator in&#xD;
             consultation with the medical monitor considers to be inappropriate to allow&#xD;
             participation in the study.&#xD;
&#xD;
          -  The subject's screening ECG shows a corrected QT interval using Fridericia's formula&#xD;
             (QTcF) of ≥ 450 msec for male subjects or ≥ 470 msec for female subjects.&#xD;
&#xD;
          -  The subject's screening hematology results show an alanine aminotransferase (ALT) or&#xD;
             aspartate aminotransferase (AST) value ≥ 2 times the upper limit of normal (ULN), or a&#xD;
             blood urea nitrogen (BUN) value ≥ 1.5 times the ULN for the reference lab.&#xD;
&#xD;
          -  Subject who is currently participating or has participated in a clinical trial within&#xD;
             the last 180 days or who participated in more than 2 clinical trials within the past&#xD;
             year. This includes studies using marketed compounds or devices.&#xD;
&#xD;
          -  Subject is at high risk of non-compliance in the investigator's opinion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>CNS Medical Director, MD</last_name>
    <role>Study Director</role>
    <affiliation>Sumitomo Pharma America, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pharmacology Research Institute</name>
      <address>
        <city>Encino</city>
        <state>California</state>
        <zip>91316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network Inc</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pharmacology Research Institute</name>
      <address>
        <city>Los Alamitos</city>
        <state>California</state>
        <zip>90720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pharmacology Research Institute</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92660-2452</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Excell Research, Inc</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuropsychiatric Research Center of Orange County</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Clinical Research Center, LLC</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Neuroscience Solutions Inc.</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Research Center</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Research Associates</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Centers of America, LLC</name>
      <address>
        <city>Oakland Park</city>
        <state>Florida</state>
        <zip>33334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research Group of Central Florida</name>
      <address>
        <city>Sanford</city>
        <state>Florida</state>
        <zip>32771</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlanta Center for Medical Research</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>iResearch Atlanta, LLC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goldpoint Clinical Research</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPS Research Company</name>
      <address>
        <city>Oklahoma City</city>
        <state>Indiana</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rochester Center for Behavioral Health</name>
      <address>
        <city>Rochester Hills</city>
        <state>Michigan</state>
        <zip>48307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Research Group</name>
      <address>
        <city>St. Charles</city>
        <state>Missouri</state>
        <zip>63301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Emotional Fitness</name>
      <address>
        <city>Cherry Hill</city>
        <state>New Jersey</state>
        <zip>08002</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brooklyn Medical Institutes, LLC</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Child and Family Study Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Clinical Research Center</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Center for Clinical Investigations, Inc.</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suburban Research Associates</name>
      <address>
        <city>Media</city>
        <state>Pennsylvania</state>
        <zip>19063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRI Lifetree</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19139</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Neuroscience Solutions</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Future Search Clinical Trials, LP</name>
      <address>
        <city>Austine</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NeuroScience, Inc</name>
      <address>
        <city>Herndon</city>
        <state>Virginia</state>
        <zip>20170</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastside Therapeutic Resource</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Research Network, LLC-Seattle</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>September 18, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>November 17, 2014</results_first_submitted>
  <results_first_submitted_qc>January 9, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 12, 2015</results_first_posted>
  <last_update_submitted>January 9, 2015</last_update_submitted>
  <last_update_submitted_qc>January 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 12, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>Attention deficit hyperactivity disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkinesis</mesh_term>
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>SEP-225289 4mg</title>
          <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
        </group>
        <group group_id="P2">
          <title>SEP-225289 8mg</title>
          <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="116"/>
                <participants group_id="P2" count="115"/>
                <participants group_id="P3" count="110"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
                <participants group_id="P2" count="59"/>
                <participants group_id="P3" count="100"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="56"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-complance with study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliant with study visits</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>SAE not related to study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent to treat population</population>
      <group_list>
        <group group_id="B1">
          <title>SEP-225289 4mg</title>
          <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily</description>
        </group>
        <group group_id="B2">
          <title>SEP-225289 8mg</title>
          <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="114"/>
            <count group_id="B2" value="107"/>
            <count group_id="B3" value="110"/>
            <count group_id="B4" value="331"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="114"/>
                    <measurement group_id="B2" value="107"/>
                    <measurement group_id="B3" value="110"/>
                    <measurement group_id="B4" value="331"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.2" spread="10.06"/>
                    <measurement group_id="B2" value="34.5" spread="11.15"/>
                    <measurement group_id="B3" value="33.9" spread="11.03"/>
                    <measurement group_id="B4" value="34.2" spread="10.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="44"/>
                    <measurement group_id="B4" value="137"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="66"/>
                    <measurement group_id="B4" value="194"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="114"/>
                    <measurement group_id="B2" value="107"/>
                    <measurement group_id="B3" value="110"/>
                    <measurement group_id="B4" value="331"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline at Week 4 in ADHD Symptoms Measured With the ADHD Rating Scale Version IV With Adult Prompts (ADHD RS IV)</title>
        <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores.</description>
        <time_frame>4 Weeks</time_frame>
        <population>Intent to treat population</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-225289 4mg</title>
            <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O2">
            <title>SEP-225289 8mg</title>
            <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 4 in ADHD Symptoms Measured With the ADHD Rating Scale Version IV With Adult Prompts (ADHD RS IV)</title>
          <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores.</description>
          <population>Intent to treat population</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="114"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.38" spread="1.07"/>
                    <measurement group_id="O2" value="-13.88" spread="1.20"/>
                    <measurement group_id="O3" value="-9.7" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The 4 mg and 8 mg SEP 225289 groups were compared to placebo using a MMRM analysis. The MMRM model included treatment, visit (as a categorical variable), pooled center, baseline ADHD RS-IV with adult prompts score, and treatment-by-visit interaction. An unstructured covariance matrix was used for the within subject correlation.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-9.7</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The 4 mg SEP 225289 group was compared to placebo using a MMRM analysis. The MMRM model included treatment, visit (as a categorical variable), pooled center, baseline ADHD RS-IV with adult prompts score, and treatment-by-visit interaction. An unstructured covariance matrix was used for the within subject correlation.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.076</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>P-values of SEP 225289 4 mg versus placebo at Week 4 was adjusted for multiple comparisons using the Hochberg procedure.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-12.38</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The 8 mg SEP 225289 group was compared to placebo using a MMRM analysis. The MMRM model included treatment, visit (as a categorical variable), pooled center, baseline ADHD RS-IV with adult prompts score, and treatment-by-visit interaction. An unstructured covariance matrix was used for the within subject correlation.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.019</p_value>
            <p_value_desc>p-value of SEP 225289 8 mg versus placebo at Week 4 was adjusted for multiple comparisons using the Hochberg procedure.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-13.88</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in ADHD Symptoms Measured With the ADHD RS IV at Weeks 1, 2, 3.</title>
        <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores (range 0 - 54).</description>
        <time_frame>Weeks 1, 2, 3</time_frame>
        <population>Intent to treat population</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-225289 4mg</title>
            <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O2">
            <title>SEP-225289 8mg</title>
            <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in ADHD Symptoms Measured With the ADHD RS IV at Weeks 1, 2, 3.</title>
          <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores (range 0 - 54).</description>
          <population>Intent to treat population</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.46" spread="0.77"/>
                    <measurement group_id="O2" value="-7.83" spread="0.8"/>
                    <measurement group_id="O3" value="-7.88" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.09" spread="0.91"/>
                    <measurement group_id="O2" value="-11.03" spread="0.97"/>
                    <measurement group_id="O3" value="-9.14" spread="0.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.16" spread="0.99"/>
                    <measurement group_id="O2" value="-12.79" spread="1.09"/>
                    <measurement group_id="O3" value="-9.62" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI S) at Weeks 1, 2, 3, 4.</title>
        <description>The CGI-S modified asked the clinician one question: Considering your total clinical experience with adult ADHD, how mentally ill is the subject at this time?&quot;.The clinician's answer was rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = ng the most extremely ill subjects.</description>
        <time_frame>Weeks 1, 2, 3, 4</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-225289 4mg</title>
            <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O2">
            <title>SEP-225289 8mg</title>
            <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI S) at Weeks 1, 2, 3, 4.</title>
          <description>The CGI-S modified asked the clinician one question: Considering your total clinical experience with adult ADHD, how mentally ill is the subject at this time?&quot;.The clinician's answer was rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = ng the most extremely ill subjects.</description>
          <population>Intent to treat</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.44" spread="0.066"/>
                    <measurement group_id="O2" value="-0.43" spread="0.069"/>
                    <measurement group_id="O3" value="-0.45" spread="0.067"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.74" spread="0.085"/>
                    <measurement group_id="O2" value="-0.74" spread="0.091"/>
                    <measurement group_id="O3" value="-0.61" spread="0.086"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.98" spread="0.091"/>
                    <measurement group_id="O2" value="-0.93" spread="0.102"/>
                    <measurement group_id="O3" value="-0.69" spread="0.092"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.08" spread="0.103"/>
                    <measurement group_id="O2" value="-1.14" spread="0.118"/>
                    <measurement group_id="O3" value="-0.74" spread="0.103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Inattentiveness and Hyperactivity Subscales of the ADHD RS IV at Weeks 1, 2, 3, 4</title>
        <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The even number items (2, 4, 6, 8, 10, 12, 14, 16, 18) assess hyperactive impulsive symptoms and the odd number items (1, 3, 5, 7, 9, 11, 13, 15, 17) assess inattentive symptoms. The ADHD inattentiveness subscale score is defined as sum of items (1, 3, 5, 7, 9, 11, 13, 15, 17) scores (range 0 - 27). The ADHD hyperactive impulsive subscale score is defined as sum of items (2, 4, 6, 8, 10, 12, 14, 16, 18) scores (range 0 - 27).</description>
        <time_frame>Weeks 1, 2, 3, 4</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-225289 4mg</title>
            <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O2">
            <title>SEP-225289 8mg</title>
            <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Inattentiveness and Hyperactivity Subscales of the ADHD RS IV at Weeks 1, 2, 3, 4</title>
          <description>The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The even number items (2, 4, 6, 8, 10, 12, 14, 16, 18) assess hyperactive impulsive symptoms and the odd number items (1, 3, 5, 7, 9, 11, 13, 15, 17) assess inattentive symptoms. The ADHD inattentiveness subscale score is defined as sum of items (1, 3, 5, 7, 9, 11, 13, 15, 17) scores (range 0 - 27). The ADHD hyperactive impulsive subscale score is defined as sum of items (2, 4, 6, 8, 10, 12, 14, 16, 18) scores (range 0 - 27).</description>
          <population>Intent to treat</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>inattentivenes Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.23" spread="0.465"/>
                    <measurement group_id="O2" value="-4.61" spread="0.483"/>
                    <measurement group_id="O3" value="-4.64" spread="0.474"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>inattentivenes Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.75" spread="0.539"/>
                    <measurement group_id="O2" value="-6.32" spread="0.581"/>
                    <measurement group_id="O3" value="-5.43" spread="0.546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>inattentivenes Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.93" spread="0.60"/>
                    <measurement group_id="O2" value="-7.03" spread="0.669"/>
                    <measurement group_id="O3" value="-5.89" spread="0.606"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>inattentivenes Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.0" spread="0.641"/>
                    <measurement group_id="O2" value="-7.97" spread="0.732"/>
                    <measurement group_id="O3" value="-5.61" spread="0.643"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>hyperactivity Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.23" spread="0.391"/>
                    <measurement group_id="O2" value="-3.20" spread="0.405"/>
                    <measurement group_id="O3" value="-3.26" spread="0.399"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>hyperactivity Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.35" spread="0.462"/>
                    <measurement group_id="O2" value="-4.71" spread="0.498"/>
                    <measurement group_id="O3" value="-3.75" spread="0.467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>hyperactivity Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.23" spread="0.496"/>
                    <measurement group_id="O2" value="-4.78" spread="0.553"/>
                    <measurement group_id="O3" value="-3.78" spread="0.501"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>hyperactivity Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.39" spread="0.536"/>
                    <measurement group_id="O2" value="-5.94" spread="0.615"/>
                    <measurement group_id="O3" value="-4.13" spread="0.536"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Responders at Weeks 1, 2, 3, 4. A Responder is Defined as a Subject With a ≥ 30% Improvement in ADHD Symptoms Compared With Baseline as Measured by the ADHD RS IV.</title>
        <time_frame>Weeks 1, 2, 3, 4</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-225289 4mg</title>
            <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O2">
            <title>SEP-225289 8mg</title>
            <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Responders at Weeks 1, 2, 3, 4. A Responder is Defined as a Subject With a ≥ 30% Improvement in ADHD Symptoms Compared With Baseline as Measured by the ADHD RS IV.</title>
          <population>Intent to treat</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="35"/>
                    <measurement group_id="O3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="39"/>
                    <measurement group_id="O3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55"/>
                    <measurement group_id="O2" value="43"/>
                    <measurement group_id="O3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="38"/>
                    <measurement group_id="O3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Wender-Reimher Adult Attention Deficit Disorder Scale (WRAADDS) as Measured at Weeks 1, 2, 3, 4.</title>
        <description>The WRAADDS measured the severity of the target symptoms of adults with ADHD. It measured symptoms in 7 categories: attention difficulties, hyperactivity/restlessness, temper, affective lability, emotional overreactivity, disorganization, and impulsivity. The scale rated individual items from 0 to 2 (0 = not present, 1 = mild, 2 = clearly present) and summarized each of the 7 categories on a 0 to 4 scale (0 = none, 1 = mild, 2 = moderate, 3 = quite a bit, 4 = very much). The WRAADDS total score is defined as sum of all 28 item subscores (range 0 - 56).</description>
        <time_frame>Weeks 1, 2, 3, 4</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-225289 4mg</title>
            <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O2">
            <title>SEP-225289 8mg</title>
            <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Wender-Reimher Adult Attention Deficit Disorder Scale (WRAADDS) as Measured at Weeks 1, 2, 3, 4.</title>
          <description>The WRAADDS measured the severity of the target symptoms of adults with ADHD. It measured symptoms in 7 categories: attention difficulties, hyperactivity/restlessness, temper, affective lability, emotional overreactivity, disorganization, and impulsivity. The scale rated individual items from 0 to 2 (0 = not present, 1 = mild, 2 = clearly present) and summarized each of the 7 categories on a 0 to 4 scale (0 = none, 1 = mild, 2 = moderate, 3 = quite a bit, 4 = very much). The WRAADDS total score is defined as sum of all 28 item subscores (range 0 - 56).</description>
          <population>Intent to treat</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.9" spread="0.783"/>
                    <measurement group_id="O2" value="-6.97" spread="0.813"/>
                    <measurement group_id="O3" value="-6.87" spread="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.85" spread="0.919"/>
                    <measurement group_id="O2" value="-9.11" spread="0.992"/>
                    <measurement group_id="O3" value="-8.10" spread="0.933"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.74" spread="0.957"/>
                    <measurement group_id="O2" value="-9.84" spread="1.07"/>
                    <measurement group_id="O3" value="-8.15" spread="0.967"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.02" spread="1.005"/>
                    <measurement group_id="O2" value="-11.91" spread="1.166"/>
                    <measurement group_id="O3" value="-8.97" spread="1.004"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From baseline to week 4 for double-blind treatment, then 2 weeks of follow-up</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SEP-225289 4mg</title>
          <description>SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
        </group>
        <group group_id="E2">
          <title>SEP-225289 8mg</title>
          <description>SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses&#xD;
SEP-225289: SEP-225289 4mg once daily&#xD;
SEP-225289: SEP-225289 8mg once daily</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>4 capsules of placebo&#xD;
Placebo: Placebo once daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Mediastinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemi</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Ectopic pregnancy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="88" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="89" subjects_at_risk="111"/>
                <counts group_id="E3" subjects_affected="65" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="116"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="116"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="111"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="116"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="111"/>
                <counts group_id="E3" events="6" subjects_affected="3" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="116"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="111"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="116"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="111"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="116"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="111"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="116"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="111"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="116"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="111"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="116"/>
                <counts group_id="E2" events="26" subjects_affected="25" subjects_at_risk="111"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="19" subjects_affected="15" subjects_at_risk="116"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="111"/>
                <counts group_id="E3" events="16" subjects_affected="12" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="116"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="111"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="116"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="116"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Combined insomniaa</sub_title>
                <counts group_id="E1" events="45" subjects_affected="40" subjects_at_risk="116"/>
                <counts group_id="E2" events="55" subjects_affected="50" subjects_at_risk="111"/>
                <counts group_id="E3" events="18" subjects_affected="17" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="32" subjects_affected="29" subjects_at_risk="116"/>
                <counts group_id="E2" events="46" subjects_affected="41" subjects_at_risk="111"/>
                <counts group_id="E3" events="12" subjects_affected="11" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="116"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="111"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Initial insomnia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="116"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="111"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Middle insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="116"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="111"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="116"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="116"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="111"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="110"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="111"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="116"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="111"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="110"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS agreement between Principal Investigator and Sponsor that restricts PI's rights to discuss or publish trial results after trial is completed.&#xD;
In addition to the &lt;60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication provided, if a multicenter publication is not forthcoming within 24 months post completion of study at all sites, PI shall be free to publish.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>1-866-503-6351</name_or_title>
      <organization>Sunovion</organization>
      <phone>1-866-503-6351</phone>
      <email>clinicaltrialdisclosure@sunvion.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01692782
org study id: SEP360-201
nct id: NCT01692782
lead sponsor: 
has dmc: Yes
A Phase 2 study of SEP-225289 in adults with attention deficit hyperactivity disorder (ADHD).
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline at Week 4 in ADHD Symptoms Measured With the ADHD Rating Scale Version IV With Adult Prompts (ADHD RS IV)
time frame: 4 Weeks
description: The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores.
measure: Change From Baseline in ADHD Symptoms Measured With the ADHD RS IV at Weeks 1, 2, 3.
time frame: Weeks 1, 2, 3
description: The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The ADHD rating scale total score is defined as sum of all 18 item scale scores (range 0 - 54).
measure: Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI S) at Weeks 1, 2, 3, 4.
time frame: Weeks 1, 2, 3, 4
description: The CGI-S modified asked the clinician one question: Considering your total clinical experience with adult ADHD, how mentally ill is the subject at this time?".The clinician's answer was rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = ng the most extremely ill subjects.
measure: Change From Baseline in the Inattentiveness and Hyperactivity Subscales of the ADHD RS IV at Weeks 1, 2, 3, 4
time frame: Weeks 1, 2, 3, 4
description: The ADHD RS-IV with adult prompts is an 18 item scale based on the DSM IV TR criteria for ADHD that provides a rating of the severity symptoms. Scoring is based on a 4 point Likert-type severity scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Clinicians scored the highest score that was generated for the prompts for each item. The even number items (2, 4, 6, 8, 10, 12, 14, 16, 18) assess hyperactive impulsive symptoms and the odd number items (1, 3, 5, 7, 9, 11, 13, 15, 17) assess inattentive symptoms. The ADHD inattentiveness subscale score is defined as sum of items (1, 3, 5, 7, 9, 11, 13, 15, 17) scores (range 0 - 27). The ADHD hyperactive impulsive subscale score is defined as sum of items (2, 4, 6, 8, 10, 12, 14, 16, 18) scores (range 0 - 27).
measure: The Number of Responders at Weeks 1, 2, 3, 4. A Responder is Defined as a Subject With a ≥ 30% Improvement in ADHD Symptoms Compared With Baseline as Measured by the ADHD RS IV.
time frame: Weeks 1, 2, 3, 4
measure: Change From Baseline in the Wender-Reimher Adult Attention Deficit Disorder Scale (WRAADDS) as Measured at Weeks 1, 2, 3, 4.
time frame: Weeks 1, 2, 3, 4
description: The WRAADDS measured the severity of the target symptoms of adults with ADHD. It measured symptoms in 7 categories: attention difficulties, hyperactivity/restlessness, temper, affective lability, emotional overreactivity, disorganization, and impulsivity. The scale rated individual items from 0 to 2 (0 = not present, 1 = mild, 2 = clearly present) and summarized each of the 7 categories on a 0 to 4 scale (0 = none, 1 = mild, 2 = moderate, 3 = quite a bit, 4 = very much). The WRAADDS total score is defined as sum of all 28 item subscores (range 0 - 56).
arm group label: SEP-225289 4mg
arm group type: Experimental
description: SEP-225289 4mg once daily taken as a combination of SEP-225289 2mg and placebo capsules to achieve 4mg QD doses
arm group label: SEP-225289 8mg
arm group type: Experimental
description: SEP-225289 8mg once daily taken as a combination of SEP-225289 2mg and placebo to achieve 8mg QD doses
arm group label: Placebo
arm group type: Placebo Comparator
description: 4 capsules of placebo
intervention type: Drug
intervention name: SEP-225289
description: SEP-225289 4mg once daily
arm group label: SEP-225289 4mg
other name: Dasotraline
intervention type: Drug
intervention name: SEP-225289
description: SEP-225289 8mg once daily
arm group label: SEP-225289 8mg
other name: Dasotraline
intervention type: Drug
intervention name: Placebo
description: Placebo once daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: CNS Medical Director, MD
role: Study Director
affiliation: Sumitomo Pharma America, Inc.
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country: United States
responsible party type: Sponsor
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 