<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/NCT03030599</url>
  </required_header>
  <id_info>
    <org_study_id>15-006</org_study_id>
    <secondary_id>2016-000426-20</secondary_id>
    <nct_id>NCT03030599</nct_id>
  </id_info>
  <brief_title>A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy</brief_title>
  <official_title>A Double-Blind, Placebo-Controlled, Randomized-Withdrawal, Multicenter Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jazz Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jazz Pharmaceuticals</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>
      This is a double-blind, placebo-controlled, randomized-withdrawal, multicenter study of the&#xD;
      efficacy and safety of JZP-258.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will be transitioned to JZP-258 based on their treatment status at study entry. All&#xD;
      subjects will begin JZP-258 treatment at the beginning of this period and continue through&#xD;
      Week 12. They will be treated with JZP-258 alone for the final two weeks of this 12-week&#xD;
      period. Once the JZP-258 dose has been optimized per the Investigator's judgment, these&#xD;
      subjects may enter the 2-week Stable-Dose Period with that dose. Subjects are eligible to&#xD;
      enter the Double-Blind Randomized-Withdrawal Period if the dose of JZP-258 remains unchanged&#xD;
      during the Stable-Dose Period and, in the judgment of the Investigator, no clinically&#xD;
      significant worsening in narcolepsy symptoms or clinically significant adverse events due to&#xD;
      JZP-258 treatment have occurred. Subjects will return for a Safety Follow-up visit 2 weeks&#xD;
      after the Double-Blind Randomized-Withdrawal Period. Subjects who complete the double-blind&#xD;
      treatment period during the Main Study are eligible to enter a 24-week Open-Label Extension.&#xD;
      During this period subjects will receive open label JZP-258. Subjects will return for a&#xD;
      Safety Follow-up visit 2 weeks after the Open-Label Extension Period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2017</start_date>
  <completion_date type="Actual">July 10, 2019</completion_date>
  <primary_completion_date type="Actual">January 24, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Weekly Number of Cataplexy Attacks</measure>
    <time_frame>Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)</time_frame>
    <description>Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the Epworth Sleepiness Scale (ESS) Score</measure>
    <time_frame>From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period</time_frame>
    <description>This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall</measure>
    <time_frame>At the end of the Double Blind Randomized Withdrawal Period</time_frame>
    <description>At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = &quot;very much improved&quot; to 7 = &quot;very much worse&quot; since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall</measure>
    <time_frame>At the end of the Double Blind Randomized Withdrawal Period</time_frame>
    <description>At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = &quot;very much improved&quot; to 7 = &quot;very much worse&quot;. This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores</measure>
    <time_frame>At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period</time_frame>
    <description>The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale</measure>
    <time_frame>At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period</time_frame>
    <description>The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">201</enrollment>
  <condition>Narcolepsy With Cataplexy</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>JZP-258</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>JZP-258</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JZP-258</intervention_name>
    <description>JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate</description>
    <arm_group_label>JZP-258</arm_group_label>
    <other_name>Xyrem®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial [United States Pharmacopeia/ National Formulary])</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects between 18 and 70 years of age, inclusive.&#xD;
&#xD;
          2. Have a primary diagnosis of narcolepsy with cataplexy that meets ICSD-3 criteria or&#xD;
             DSM-5 criteria, and currently untreated or treated with or without anticataplectics.&#xD;
&#xD;
          3. If applicable, treated with a stimulant or alerting agent at unchanged doses for at&#xD;
             least 2 months prior to dosing or not treated with a stimulant or alerting agent.&#xD;
&#xD;
          4. Willing and able to comply with the study design schedule and other requirements.&#xD;
&#xD;
          5. Willing and able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Narcolepsy secondary to another medical condition (e.g., CNS injury or lesion)&#xD;
&#xD;
          2. History or presence of any unstable or clinically significant medical condition,&#xD;
             behavioral or psychiatric disorder (including active suicidal ideation), or history or&#xD;
             presence of another neurological disorder or surgical history that might affect the&#xD;
             subject's safety and/or interfere with the conduct of the study in the opinion of the&#xD;
             Investigator.&#xD;
&#xD;
          3. Treatment with any central nervous system sedating agents, including but not limited&#xD;
             to benzodiazepines, nonbenzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics,&#xD;
             opioids, barbiturates, phenytoin, ethosuximide, or MCT inhibitors, e.g. diclofenac,&#xD;
             valproate, ibuprofen, within 2 weeks prior to enrollment (discontinuation for the&#xD;
             purpose of study enrollment is permitted only if considered safe by the Investigator&#xD;
             and approved by the Medical Monitor).&#xD;
&#xD;
          4. Treatment with an antidepressant for cataplexy, if the withdrawal of the&#xD;
             antidepressant during cross-titration with JZP-258 might be unsafe due to prior&#xD;
             history of depression.&#xD;
&#xD;
          5. Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the&#xD;
             Investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Director Clinical Trial Disclosure &amp; Transparency</last_name>
    <role>Study Director</role>
    <affiliation>Jazz Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SDS Clinical Trials, Inc.</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92858</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Health Services</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Sleep Institute</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Disease Specialists</name>
      <address>
        <city>Kissimmee</city>
        <state>Florida</state>
        <zip>34741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Neurological Center</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kentucky Research Group</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Sleep &amp; Wake Disorders</name>
      <address>
        <city>Chevy Chase</city>
        <state>Maryland</state>
        <zip>20815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore/ Sleep-Wake Disorders Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastonia Medical Specialty Clinic</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Carolina</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intrepid Research</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45245</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic, Sleep Disorder Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Antwerpen</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Ostrava</name>
      <address>
        <city>Ostrava-Poruba</city>
        <zip>70800</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vseobecna fakultni nemocnice v Praze</name>
      <address>
        <city>Praha 2</city>
        <zip>128 21</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsingin Uniklinikka, Vitalmed Oy</name>
      <address>
        <city>Helsinki</city>
        <zip>00380</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Gui de Chauliac</name>
      <address>
        <city>Montpellier</city>
        <state>Herault</state>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Roger Salengro - CHU Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic i Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Castellón</name>
      <address>
        <city>Castelló</city>
        <zip>12004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Investigaciones del Sueño</name>
      <address>
        <city>Madrid</city>
        <zip>28036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vithas Nuestra Señora de America</name>
      <address>
        <city>Madrid</city>
        <zip>28043</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czechia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Croatia</country>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <results_first_submitted>August 20, 2020</results_first_submitted>
  <results_first_submitted_qc>November 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 12, 2020</results_first_posted>
  <disposition_first_submitted>February 7, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>November 10, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">November 12, 2020</disposition_first_posted>
  <last_update_submitted>November 10, 2020</last_update_submitted>
  <last_update_submitted_qc>November 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Narcolepsy</mesh_term>
    <mesh_term>Cataplexy</mesh_term>
  </condition_browse>
  <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>May 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03030599/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>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>February 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03030599/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Subjects were evaluated for eligibility during the Screening Period (up to 30 days).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Open-label JZP-258</title>
          <description>All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period.</description>
        </group>
        <group group_id="P2">
          <title>JZP-258</title>
          <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>A matching oral solution to JZP-258.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Open Label Treatment and Titration</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="201"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="155"/>
                <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="46"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</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>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </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="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance with Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="0"/>
                <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="6"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <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="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Stable Dose</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="149">149 subjects of the 201 entered the Stable Dose Period. Of those subjects, 136 were randomized.</participants>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="144"/>
                <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>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</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>Lost to Follow-up</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_list>
        </period>
        <period>
          <title>Double Blind Randomized Withdrawal</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="69">134 of the 136 subjects randomized received at least 1 dose of study drug in the DB RWP.</participants>
                <participants group_id="P3" count="67">134 of the 136 subjects randomized received at least 1 dose of study drug in the DB RWP.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="69"/>
                <participants group_id="P3" count="59"/>
              </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="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized in error</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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_list>
        </period>
        <period>
          <title>Open-label Extension</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="67"/>
                <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="7"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <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="0"/>
                <participants group_id="P3" count="0"/>
              </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="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other Reason</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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Open Label Treatment and Titration</title>
          <description>All 201 subjects entered the Open Label Optimized Treatment and Titration Period (OL OTTP) and received at least 1 dose of study drug. During the OL OTTP (12 weeks), eligible subjects were transitioned to JZP-258 treatment based on their pre-treatment status. During the Stable Dose Period, subjects received open-label JZP-258 at the same unchanged dose that they received during the last 2 weeks of the Open Label Treatment and Titration Period.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="201"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="195"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="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="122"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="177"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Weekly Number of Cataplexy Attacks</title>
        <description>Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.</description>
        <time_frame>Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)</time_frame>
        <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>JZP-258</title>
            <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>A matching oral solution to JZP-258.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Weekly Number of Cataplexy Attacks</title>
          <description>Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.</description>
          <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
          <units>attacks</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="-0.49" upper_limit="1.75"/>
                    <measurement group_id="O2" value="2.35" lower_limit="0.00" upper_limit="11.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Epworth Sleepiness Scale (ESS) Score</title>
        <description>This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.</description>
        <time_frame>From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period</time_frame>
        <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>JZP-258</title>
            <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>A matching oral solution to JZP-258.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Epworth Sleepiness Scale (ESS) Score</title>
          <description>This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.</description>
          <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="-1.0" upper_limit="1.0"/>
                    <measurement group_id="O2" value="2.0" lower_limit="0.00" upper_limit="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall</title>
        <description>At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = &quot;very much improved&quot; to 7 = &quot;very much worse&quot; since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).</description>
        <time_frame>At the end of the Double Blind Randomized Withdrawal Period</time_frame>
        <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>JZP-258</title>
            <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>A matching oral solution to JZP-258.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall</title>
          <description>At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = &quot;very much improved&quot; to 7 = &quot;very much worse&quot; since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).</description>
          <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall</title>
        <description>At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = &quot;very much improved&quot; to 7 = &quot;very much worse&quot;. This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.</description>
        <time_frame>At the end of the Double Blind Randomized Withdrawal Period</time_frame>
        <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>JZP-258</title>
            <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>A matching oral solution to JZP-258.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall</title>
          <description>At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = &quot;very much improved&quot; to 7 = &quot;very much worse&quot;. This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.</description>
          <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores</title>
        <description>The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.</description>
        <time_frame>At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period</time_frame>
        <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>JZP-258</title>
            <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>A matching oral solution to JZP-258.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores</title>
          <description>The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.</description>
          <population>The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="67"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Component Summary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" lower_limit="-2.07" upper_limit="2.41"/>
                    <measurement group_id="O2" value="-1.92" lower_limit="-3.46" upper_limit="1.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mental Component Summary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.55" lower_limit="-1.88" upper_limit="3.78"/>
                    <measurement group_id="O2" value="-1.92" lower_limit="-6.28" upper_limit="1.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale</title>
        <description>The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).</description>
        <time_frame>At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period</time_frame>
        <population>There were 68 JZP-258 participants included in the Crosswalk Index, and 69 JZP-258 participants in the VAS Score. The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>JZP-258</title>
            <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>A matching oral solution to JZP-258.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale</title>
          <description>The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).</description>
          <population>There were 68 JZP-258 participants included in the Crosswalk Index, and 69 JZP-258 participants in the VAS Score. The efficacy population contains all randomized subjects who received at least one dose of double-blind study drug and had at least one set of post-randomization efficacy data.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crosswalk index</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="68"/>
                    <count group_id="O2" value="65"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="-0.01" upper_limit="0.03"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-0.05" upper_limit="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS Score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="69"/>
                    <count group_id="O2" value="65"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="5.00"/>
                    <measurement group_id="O2" value="-5.00" lower_limit="-10.00" upper_limit="5.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through week 18 or early termination.</time_frame>
      <desc>Safety data are summarized for all subjects who received at least 1 dose of study medication across all periods.</desc>
      <group_list>
        <group group_id="E1">
          <title>JZP-258</title>
          <description>JZP-258 at the dose taken during the last 2 weeks of the Stable Dose Period.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>A matching oral solution to JZP-258.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Viral cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Muscle enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Invasive ductal breast carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral nerve paresis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.1)</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="108" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </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="15" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cataplexy</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="65"/>
              </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>The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Clinical Trial Disclosure &amp; Transparency</name_or_title>
      <organization>Jazz Pharmaceuticals</organization>
      <phone>2158709177</phone>
      <email>ClinicalTrialDisclosure@JazzPharma.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/NCT03030599
org study id: 15-006
secondary id: 2016-000426-20
nct id: NCT03030599
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a double-blind, placebo-controlled, randomized-withdrawal, multicenter study of the
      efficacy and safety of JZP-258.
Subjects will be transitioned to JZP-258 based on their treatment status at study entry. All
      subjects will begin JZP-258 treatment at the beginning of this period and continue through
      Week 12. They will be treated with JZP-258 alone for the final two weeks of this 12-week
      period. Once the JZP-258 dose has been optimized per the Investigator's judgment, these
      subjects may enter the 2-week Stable-Dose Period with that dose. Subjects are eligible to
      enter the Double-Blind Randomized-Withdrawal Period if the dose of JZP-258 remains unchanged
      during the Stable-Dose Period and, in the judgment of the Investigator, no clinically
      significant worsening in narcolepsy symptoms or clinically significant adverse events due to
      JZP-258 treatment have occurred. Subjects will return for a Safety Follow-up visit 2 weeks
      after the Double-Blind Randomized-Withdrawal Period. Subjects who complete the double-blind
      treatment period during the Main Study are eligible to enter a 24-week Open-Label Extension.
      During this period subjects will receive open label JZP-258. Subjects will return for a
      Safety Follow-up visit 2 weeks after the Open-Label Extension Period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Weekly Number of Cataplexy Attacks
time frame: Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)
description: Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.
measure: Change in the Epworth Sleepiness Scale (ESS) Score
time frame: From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period
description: This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.
measure: Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall
time frame: At the end of the Double Blind Randomized Withdrawal Period
description: At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).
measure: Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall
time frame: At the end of the Double Blind Randomized Withdrawal Period
description: At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.
measure: Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores
time frame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period
description: The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.
measure: Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale
time frame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period
description: The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
arm group label: JZP-258
arm group type: Experimental
description: JZP-258
intervention type: Drug
intervention name: JZP-258
description: JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate
arm group label: JZP-258
other name: Xyrem®
intervention type: Other
intervention name: Placebo
description: Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial [United States Pharmacopeia/ National Formulary])
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Director Clinical Trial Disclosure & Transparency
role: Study Director
affiliation: Jazz Pharmaceuticals
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country: Belgium
country: Czechia
country: Finland
country: France
country: Spain
country: United States
country: Croatia
country: Germany
country: Netherlands
country: Poland
country: Switzerland
country: United Kingdom
responsible party type: Sponsor
mesh term: Narcolepsy
mesh term: Cataplexy
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 