<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/NCT03292952</url>
  </required_header>
  <id_info>
    <org_study_id>KP415.E01</org_study_id>
    <nct_id>NCT03292952</nct_id>
  </id_info>
  <brief_title>KP415 Classroom Study in Children (6-12 Years of Age) With ADHD</brief_title>
  <official_title>A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled, Parallel Efficacy Laboratory Classroom Study With KP415 in Children With Attention-Deficit/Hyperactivity Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zevra Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zevra Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is a multicenter, dose-optimized, double-blind, randomized, placebo-controlled,&#xD;
      parallel efficacy laboratory classroom study with KP415 in children with&#xD;
      Attention-Deficit/Hyperactivity Disorder (ADHD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will consist of a Screening Period, an Open-Label Dose Optimization Phase, a&#xD;
      Double-Blind Treatment Phase and a Follow-Up Visit, as follows:&#xD;
&#xD;
        -  Screening Period: Subjects will undergo a screening period up to 49 days prior to&#xD;
           entering into the Open-Label Dose Optimization Phase.&#xD;
&#xD;
        -  Open-Label Dose Optimization Phase: During the Dose Optimization Phase, subjects will be&#xD;
           titrated to doses of 20, 30 or 40 mg KP415 based on tolerability and best individual&#xD;
           dose-response in the opinion of the Investigator.&#xD;
&#xD;
        -  Double-Blind Treatment Phase: Eligible subjects will be randomized to receive single&#xD;
           daily doses of KP415 or Placebo for 7 days according to a randomization schedule. The&#xD;
           dose of KP415 given in the Treatment Phase will be the same as the optimized dose of&#xD;
           KP415 at the end of the Dose Optimization Phase. All subjects will receive their&#xD;
           assigned treatment daily for 7 days. The dose will be the same at each day of the&#xD;
           Treatment Period. Efficacy and safety assessments will be performed after the last dose&#xD;
           of the Treatment Period.&#xD;
&#xD;
        -  Follow-Up Visit: 3 ±2 days after administration of the last dose of the Treatment Phase,&#xD;
           subjects will enter a Follow-Up Visit to evaluate safety parameters.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2017</start_date>
  <completion_date type="Actual">May 16, 2018</completion_date>
  <primary_completion_date type="Actual">May 16, 2018</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>3-week, open-label dose-optimization phase followed by a 1-week randomized, double-blind treatment phase</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores</measure>
    <time_frame>Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase</time_frame>
    <description>The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A)</measure>
    <time_frame>Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase</time_frame>
    <description>The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">155</enrollment>
  <condition>ADHD</condition>
  <arm_group>
    <arm_group_label>Double-blind KP415</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule:&#xD;
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Double-blind Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral capsule</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open-Label KP415</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule:&#xD;
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KP415 oral capsule</intervention_name>
    <description>Daily dose</description>
    <arm_group_label>Double-blind KP415</arm_group_label>
    <arm_group_label>Open-Label KP415</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Daily dose</description>
    <arm_group_label>Double-blind Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject must meet Diagnostic and Statistical Manual of Mental Disorders - Fifth&#xD;
             Edition (DSM-5) criteria for a primary diagnosis of ADHD (combined, inattentive, or&#xD;
             hyperactive/impulsive presentation) per clinical evaluation and confirmed by the Mini&#xD;
             International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).&#xD;
&#xD;
          2. Subject must have a score of at least 3 (mildly ill) on the clinician-administered&#xD;
             Clinical Global Impressions-Severity (CGI-S) scale.&#xD;
&#xD;
          3. Subject, subject's parent/legal guardian and caregiver (if applicable) must understand&#xD;
             and be willing and able to comply with all study procedures and visit schedule.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject with any clinically significant chronic medical condition that may interfere&#xD;
             with the participant's ability to participate in the study.&#xD;
&#xD;
          2. Subject has any diagnosis of bipolar I or II disorder, major depressive disorder,&#xD;
             conduct disorder, obsessive-compulsive disorder, any history of psychosis, autism&#xD;
             spectrum disorder, disruptive mood dysregulation disorder (DMDD), intellectual&#xD;
             disability, Tourette's Syndrome, confirmed genetic disorder with cognitive and/or&#xD;
             behavioral disturbances.&#xD;
&#xD;
          3. Subject has evidence of any chronic disease of the central nervous system (CNS) such&#xD;
             as tumors, inflammation, seizure disorder, vascular disorder, potential CNS related&#xD;
             disorders that might occur in childhood, or history of persistent neurological&#xD;
             symptoms attributable to serious head injury.&#xD;
&#xD;
          4. Subject has a current (last month) psychiatric diagnosis other than specific phobia,&#xD;
             motor skills disorders, oppositional defiant disorder, sleep disorders, elimination&#xD;
             disorders, adjustment disorders, learning disorders, or communication disorders.&#xD;
             Participants with school phobia or separation anxiety will not be eligible.&#xD;
&#xD;
          5. Subject has any history of attempted suicide or clinically significant suicidal&#xD;
             ideation or subject has a C-SSRS score for suicidal ideation ≥2.&#xD;
&#xD;
          6. Subject has any clinically significant unstable medical abnormality, chronic disease,&#xD;
             or a history of a clinically significant abnormality of the cardiovascular,&#xD;
             gastrointestinal, respiratory, hepatic, or renal systems, or a disorder or history of&#xD;
             a condition that may interfere with drug absorption, distribution, metabolism, or&#xD;
             excretion of study drug.&#xD;
&#xD;
          7. Subject has a history or presence of abnormal ECGs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott H Kollins, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Clinical Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Psychiatry and Behavioral Medicine, Inc.</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bayou City Research, Ltd.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <results_first_submitted>March 29, 2021</results_first_submitted>
  <results_first_submitted_qc>June 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 30, 2021</results_first_posted>
  <disposition_first_submitted>May 16, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>June 29, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 30, 2021</disposition_first_posted>
  <last_update_submitted>June 29, 2021</last_update_submitted>
  <last_update_submitted_qc>June 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03292952/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan: Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03292952/SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan: Statistical Analysis Plan Addendum</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03292952/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Open-Label KP415</title>
          <description>Open-label titration with KP415 capsule 20, 30, or 40 mg once-daily for 3 weeks</description>
        </group>
        <group group_id="P2">
          <title>Double-Blind KP415</title>
          <description>KP415 oral capsule 20, 30 or 40 mg&#xD;
KP415 oral capsule: Daily dose</description>
        </group>
        <group group_id="P3">
          <title>Double-Blind Placebo</title>
          <description>Placebo oral capsule&#xD;
Placebo oral capsule: Daily dose</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Open-Label Dose Optimization</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="155"/>
                <participants group_id="P2" count="0">All subjects were treated with open-label KP415 during the Open-Label Phase</participants>
                <participants group_id="P3" count="0">All subjects were treated with open-label KP415 during the Open-Label Phase</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="150"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Double-Blind Treatment Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0">Subjects were randomized to the double-blind Treatment Phase after Open-Label Dose Optimization</participants>
                <participants group_id="P2" count="74"/>
                <participants group_id="P3" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="74"/>
                <participants group_id="P3" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active Treatment</title>
          <description>KP415 oral capsule 20, 30 or 40 mg&#xD;
KP415 oral capsule: Daily dose</description>
        </group>
        <group group_id="B2">
          <title>Placebo Treatment</title>
          <description>Placebo oral capsule&#xD;
Placebo oral capsule: Daily dose</description>
        </group>
        <group group_id="B3">
          <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="74"/>
            <count group_id="B2" value="76"/>
            <count group_id="B3" value="150"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="9.6" spread="1.6"/>
                    <measurement group_id="B2" value="9.6" spread="1.5"/>
                    <measurement group_id="B3" value="9.6" spread="1.6"/>
                  </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="30"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="74"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores</title>
        <description>The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment.</description>
        <time_frame>Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active Treatment</title>
            <description>KP415 oral capsule 20, 30 or 40 mg&#xD;
KP415 oral capsule: Daily dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo Treatment</title>
            <description>Placebo oral capsule&#xD;
Placebo oral capsule: Daily dose</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores</title>
          <description>The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment.</description>
          <units>score 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="74"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.87" spread="0.62"/>
                    <measurement group_id="O2" value="0.536" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A)</title>
        <description>The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome.</description>
        <time_frame>Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Double-Blind KP415</title>
            <description>KP415 oral capsule 20, 30 or 40 mg&#xD;
KP415 oral capsule: Daily dose</description>
          </group>
          <group group_id="O2">
            <title>Double-Blind Placebo</title>
            <description>Placebo oral capsule&#xD;
Placebo oral capsule: Daily dose</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A)</title>
          <description>The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome.</description>
          <units>score 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="74"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.82" spread="3.44"/>
                    <measurement group_id="O2" value="2.25" spread="3.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>5 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open-Label KP415</title>
          <description>3-week titration period to identify an optimal dose of KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule, once-daily:&#xD;
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)</description>
        </group>
        <group group_id="E2">
          <title>Double-Blind KP415</title>
          <description>Optimized dose of KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule, once-daily:&#xD;
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)</description>
        </group>
        <group group_id="E3">
          <title>Double-Blind Placebo</title>
          <description>Double-Blind Placebo, once-daily</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <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="104" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="76"/>
              </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 NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gerald Orehostky</name_or_title>
      <organization>KemPharm</organization>
      <phone>321-250-3699</phone>
      <email>gorehostky@kempharm.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/NCT03292952
org study id: KP415.E01
nct id: NCT03292952
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study is a multicenter, dose-optimized, double-blind, randomized, placebo-controlled,
      parallel efficacy laboratory classroom study with KP415 in children with
      Attention-Deficit/Hyperactivity Disorder (ADHD).
The study will consist of a Screening Period, an Open-Label Dose Optimization Phase, a
      Double-Blind Treatment Phase and a Follow-Up Visit, as follows:

        -  Screening Period: Subjects will undergo a screening period up to 49 days prior to
           entering into the Open-Label Dose Optimization Phase.

        -  Open-Label Dose Optimization Phase: During the Dose Optimization Phase, subjects will be
           titrated to doses of 20, 30 or 40 mg KP415 based on tolerability and best individual
           dose-response in the opinion of the Investigator.

        -  Double-Blind Treatment Phase: Eligible subjects will be randomized to receive single
           daily doses of KP415 or Placebo for 7 days according to a randomization schedule. The
           dose of KP415 given in the Treatment Phase will be the same as the optimized dose of
           KP415 at the end of the Dose Optimization Phase. All subjects will receive their
           assigned treatment daily for 7 days. The dose will be the same at each day of the
           Treatment Period. Efficacy and safety assessments will be performed after the last dose
           of the Treatment Period.

        -  Follow-Up Visit: 3 ±2 days after administration of the last dose of the Treatment Phase,
           subjects will enter a Follow-Up Visit to evaluate safety parameters.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 3-week, open-label dose-optimization phase followed by a 1-week randomized, double-blind treatment phase
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores
time frame: Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase
description: The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment.
measure: Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A)
time frame: Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase
description: The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome.
arm group label: Double-blind KP415
arm group type: Experimental
description: KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule:
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)
arm group label: Double-blind Placebo
arm group type: Placebo Comparator
description: Placebo oral capsule
arm group label: Open-Label KP415
arm group type: Experimental
description: KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule:
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)
intervention type: Drug
intervention name: KP415 oral capsule
description: Daily dose
arm group label: Double-blind KP415
arm group label: Open-Label KP415
intervention type: Drug
intervention name: Placebo oral capsule
description: Daily dose
arm group label: Double-blind Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: No
last name: Scott H Kollins, PhD
role: Principal Investigator
affiliation: Duke Clinical Research Institute
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 