<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/NCT03836001</url>
  </required_header>
  <id_info>
    <org_study_id>49084</org_study_id>
    <nct_id>NCT03836001</nct_id>
  </id_info>
  <brief_title>A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in Patients With Epidermolysis Bullosa</brief_title>
  <official_title>A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in Patients With Epidermolysis Bullosa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Epidermolysis Bullosa Research Partnership</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Menlo Therapeutics</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine if Serlopitant (when taken by mouth) is safe and works on itch in patients aged&#xD;
      13 and above with EB.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigator will determine whether more patients taking serlopitant 5 mg daily as&#xD;
      compared to placebo can achieve at least a 3-point reduction in the 24-hour Average Itch&#xD;
      Numeric Rating Scale (NRS) following two months of treatment.&#xD;
&#xD;
      Secondary objectives include;&#xD;
&#xD;
        1. comparative weekly change in daily worst itch NRS,&#xD;
&#xD;
        2. comparative weekly change in daily average itch NRS,&#xD;
&#xD;
        3. the proportion of patients who achieve at least 30% or 50% reduction in Average Itch NRS&#xD;
           at month 2,&#xD;
&#xD;
        4. proportion of patients achieving 2-point and 4-point reductions in Average Itch NRS at&#xD;
           month 2,&#xD;
&#xD;
        5. Patient Global Impression of Change (PGIC) at month 2, the change in participant static&#xD;
           assessment of itch at month 2, and&#xD;
&#xD;
        6. assessment of the safety of serlopitant in adolescents (≥13 y.o.) and adults with&#xD;
           epidermolysis bullosa-related itch.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 18, 2019</start_date>
  <completion_date type="Actual">June 24, 2022</completion_date>
  <primary_completion_date type="Actual">December 6, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is an investigator-initiated, single-center, randomized, double-blind, placebo-controlled, parallel-arm trial evaluating the effects of serlopitant at 5 mg by mouth daily on EB-related itch.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>This is a double-blind study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients Who Achieve at Least a 3-point Reduction in AI-NRS.</measure>
    <time_frame>baseline and after two months of treatment</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Achieve at Least a 2-point Reduction in AI-NRS.</measure>
    <time_frame>baseline and after two months of treatment</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Achieve at Least a 4-point Reduction in AI-NRS.</measure>
    <time_frame>baseline and after two months of treatment</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Achieve at Least a 30% Reduction in AI-NRS.</measure>
    <time_frame>baseline and after two months of treatment</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Achieve at Least a 50% Reduction in AI-NRS.</measure>
    <time_frame>baseline and after two months of treatment</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weekly Worst Itch NRS</measure>
    <time_frame>baseline and week 1, 2, 3, 4, 5, 6, 7, and 8</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their worst itch numeric rating scale (WI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weekly AI-NRS</measure>
    <time_frame>baseline and week 1, 2, 3, 4, 5, 6, 7, and 8</time_frame>
    <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change (PGIC)</measure>
    <time_frame>month 2</time_frame>
    <description>PGIC categorized as &quot;Very much better&quot;, &quot;Moderately better&quot;, &quot;A little better&quot;, &quot;No change&quot;, &quot;A little worse&quot;, &quot;Moderately worse&quot;, and &quot;Very much worse&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Static Participant Assessment of Itch</measure>
    <time_frame>month 2</time_frame>
    <description>Severity of itch over past 7 days assessed as Very Severe, Severe, Moderate, Mild, or None.&#xD;
Change is reported as the number of participants with 3-category improvement, 2-category improvement, 1-category improvement, no change, or worse.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Epidermolysis Bullosa</condition>
  <arm_group>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will undergo two months of dosing with a placebo (inactive drug or sugar pill), followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Serlopitant Tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will undergo two months of Serlopitant 5mg daily per oral, followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Serlopitant Tablet</intervention_name>
    <description>Serlopitant is a small molecule, highly selective NK1-R (neurokinin-1 receptor) antagonist. Two critical mediators of the urge to scratch are Substance P, or SP, and its receptor, NK1-R. SP is a naturally occurring peptide in the tachykinin neuropeptide family. Tachykinins have a broad range of functions in the nervous and immune systems. SP binding of NK1-R has been shown to be a key mediator of sensory nerve signaling, including the itch-scratch reflex and the vomiting reflex.</description>
    <arm_group_label>Serlopitant Tablet</arm_group_label>
    <other_name>VPD-737</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>The placebo is a tablet that looks like a drug but has no drug or other active ingredient in it.</description>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females who are at least 13 years of age.&#xD;
&#xD;
          2. Willing and able to understand and sign informed assent/consent. Adolescents will need&#xD;
             a parent or guardian willing and able to give consent.&#xD;
&#xD;
          3. Clinical diagnosis of epidermolysis bullosa (dystrophic, junctional or simplex).&#xD;
&#xD;
          4. History of chronic pruritus of at least 6 weeks in duration&#xD;
&#xD;
          5. On the Screening Visit or Screening phone call, patients must have an NRS pruritus&#xD;
             score of at least 5 on average itch score in the past 24 hours&#xD;
&#xD;
          6. Female subjects must be of non-childbearing potential (ie, post-menopausal for at&#xD;
             least 1 year, had a hysterectomy, or had a tubal ligation) or, if of childbearing&#xD;
             potential, must have a confirmed negative urine pregnancy test prior to study&#xD;
             treatment and be willing to use effective contraception for the duration of the trial.&#xD;
             Effective contraception is defined as follows: oral/implant/injectable/ transdermal&#xD;
             contraceptives, intrauterine device, condom with spermicide, or diaphragm with&#xD;
             spermicide. Abstinence or partner's vasectomy is acceptable if the female agrees to&#xD;
             use effective contraception if she decides to discontinue abstinence or to have sexual&#xD;
             intercourse with a non-vasectomized partner.&#xD;
&#xD;
          7. Judged to be in good health based upon the results of a physical examination, medical&#xD;
             history, and safety laboratory tests.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have any medical condition or disability that would interfere with the assessment of&#xD;
             safety or efficacy in this trial or would compromise the ability of the subject to&#xD;
             travel to Stanford or to undergo study procedures or to give informed consent.&#xD;
&#xD;
          2. Have a history of sensitivity to any components of the study material.&#xD;
&#xD;
          3. Are females of childbearing potential who are unwilling to use adequate contraception&#xD;
             or who are breast feeding.&#xD;
&#xD;
          4. Have any chronic or acute medical condition that, in the opinion of the investigator,&#xD;
             might interfere with the study results or place the subject at undue risk.&#xD;
&#xD;
          5. Have chronic renal disease, i.e., serum creatinine greater than 2 times the upper&#xD;
             limit of normal.&#xD;
&#xD;
          6. Have chronic liver disease. Subjects with hepatitis B and C who have normal liver&#xD;
             function may be enrolled.&#xD;
&#xD;
          7. Have a current malignancy (such as Hodgkin's lymphoma, B or T cell lymphoma, or&#xD;
             myeloma) or blood cell dyscrasia (e.g., polycythemia or myelofibrosis) that would lead&#xD;
             to systemic chronic pruritus.&#xD;
&#xD;
          8. Have a history of thyroid cancer, thyroid nodules, inadequately treated thyroid&#xD;
             disease, or abnormal TSH or free T4 at screening.&#xD;
&#xD;
          9. Have a history of abnormalities in adrenal or pituitary function (pituitary adenoma,&#xD;
             adrenal insufficiency, or adrenal nodule).&#xD;
&#xD;
         10. Screening cortisol level &lt; 3 mcg/dL&#xD;
&#xD;
         11. Unevaluated abnormalities in cortisol, ACTH, or prolactin.&#xD;
&#xD;
         12. Have pruritus of psychogenic etiology (delusions of parasitosis, obsessive compulsive&#xD;
             disorder and major depression) or neuropathic etiology (due to shingles, spinal cord&#xD;
             injury or with neurologic deficit).&#xD;
&#xD;
         13. Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosacea&#xD;
             or tinea or active human immunodeficiency virus [HIV]). Note: Subjects with HIV who&#xD;
             have undetectable viral load, and stable retro-viral therapy may enroll.&#xD;
&#xD;
         14. Have taken investigational medications within 30 days prior to Screening.&#xD;
&#xD;
         15. Are unwilling to discontinue specific medications that, in the view of the&#xD;
             investigator may have significant interactions with the trial drug, for at least two&#xD;
             weeks prior to initiation of study and throughout the study period (this includes&#xD;
             miconazole, delavirdine, conivaptan, Clarithromycin, telithromycin, nefazodone,&#xD;
             itraconazole, ketoconazole, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir).&#xD;
&#xD;
         16. Are unable or unwilling to maintain their current anti-itch and opioid-based pain&#xD;
             medications at a stable dosage through the course of the two months of active&#xD;
             treatment (including but not limited to opioid pain medications, antihistamines, and&#xD;
             gabapentin)&#xD;
&#xD;
         17. Started or changed medications, creams, or emollients including over-the-counter (OTC)&#xD;
             preparations or bath oil treatment specifically for relief of pruritus within 30 days&#xD;
             prior to Screening.&#xD;
&#xD;
         18. Within in the past 12 months, have expressed suicidal ideation with some intent to&#xD;
             act.&#xD;
&#xD;
         19. Have any social or medical condition (e.g. alcoholism, drug dependency, psychotic&#xD;
             state) that, in the investigator's opinion, might interfere with the subject's ability&#xD;
             to comply with the requirements of the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Albert S Chiou, MD/MBA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Redwood City</city>
        <state>California</state>
        <zip>94063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <results_first_submitted>November 30, 2022</results_first_submitted>
  <results_first_submitted_qc>November 30, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 23, 2022</results_first_posted>
  <last_update_submitted>January 21, 2023</last_update_submitted>
  <last_update_submitted_qc>January 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Albert Chiou</investigator_full_name>
    <investigator_title>Assistant Professor of Dermatology.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epidermolysis Bullosa</mesh_term>
    <mesh_term>Pruritus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Serlopitant</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT03836001/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Four participants were consented but failed initial screening and were not allocated to treatment. Two participants failed initial screening but were re-screened and entered the study.&#xD;
A protocol amendment in May 2020 changed the duration of the follow-up period from 12 months to 3 months.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo Oral Tablet</title>
          <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
        </group>
        <group group_id="P2">
          <title>Serlopitant Tablet</title>
          <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
        </group>
        <group group_id="P3">
          <title>Open-label Extension</title>
          <description>3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Blinded Phase (2 Months)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <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="0"/>
                <participants group_id="P2" count="1"/>
                <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="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout (1 Month)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12">6 participants continued into the open label extension.</participants>
                <participants group_id="P2" count="10">4 participants continued into the open label extension.</participants>
                <participants group_id="P3" count="0"/>
              </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="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Open-label Extension (3 or 12 Months)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Entered 12-month Follow-up Period</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Entered 3-month Follow-up Period</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>
              <title>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>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Enrolled in other clinical study</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_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo Oral Tablet</title>
          <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
        </group>
        <group group_id="B2">
          <title>Serlopitant Tablet</title>
          <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</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="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" lower_limit="18" upper_limit="67"/>
                    <measurement group_id="B2" value="22" lower_limit="13" upper_limit="73"/>
                    <measurement group_id="B3" value="31" lower_limit="13" upper_limit="73"/>
                  </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="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </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="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="17"/>
                  </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/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>African American</title>
              <category_list>
                <category>
                  <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>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Epidermolysis Bullosa (EB) Subtype</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>EB simplex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Junctional EB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dominant dystrophic EB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Recessive dystrophic EB</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Average Itch Numeric Rating Scale (AI-NRS)</title>
          <description>Scale range: 0 to 10, higher scores mean more itch.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6" lower_limit="2" upper_limit="8"/>
                    <measurement group_id="B2" value="7" lower_limit="1" upper_limit="9"/>
                    <measurement group_id="B3" value="6" lower_limit="1" upper_limit="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Who Achieve at Least a 3-point Reduction in AI-NRS.</title>
        <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and after two months of treatment</time_frame>
        <population>Data were analyzed using the last observation carried forward method (LCOF)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieve at Least a 3-point Reduction in AI-NRS.</title>
          <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Data were analyzed using the last observation carried forward method (LCOF)</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="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </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>0.59</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Achieve at Least a 2-point Reduction in AI-NRS.</title>
        <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and after two months of treatment</time_frame>
        <population>Data were analyzed using the last observation carried forward method (LCOF)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieve at Least a 2-point Reduction in AI-NRS.</title>
          <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Data were analyzed using the last observation carried forward method (LCOF)</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="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </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>1</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Achieve at Least a 4-point Reduction in AI-NRS.</title>
        <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and after two months of treatment</time_frame>
        <population>Data were analyzed using the last observation carried forward method (LCOF)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieve at Least a 4-point Reduction in AI-NRS.</title>
          <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Data were analyzed using the last observation carried forward method (LCOF)</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="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </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>1</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Achieve at Least a 30% Reduction in AI-NRS.</title>
        <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and after two months of treatment</time_frame>
        <population>Data were analyzed using the last observation carried forward method (LCOF)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieve at Least a 30% Reduction in AI-NRS.</title>
          <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Data were analyzed using the last observation carried forward method (LCOF)</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="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </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>0.67</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Achieve at Least a 50% Reduction in AI-NRS.</title>
        <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and after two months of treatment</time_frame>
        <population>Data were analyzed using the last observation carried forward method (LCOF)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieve at Least a 50% Reduction in AI-NRS.</title>
          <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Data were analyzed using the last observation carried forward method (LCOF)</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="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </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>1</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weekly Worst Itch NRS</title>
        <description>Participants will be asked to complete a daily itch diary with their worst itch numeric rating scale (WI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and week 1, 2, 3, 4, 5, 6, 7, and 8</time_frame>
        <population>Daily diary data were averaged weekly. The missing weekly data have been imputed by the mean WI-NRS value of each participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Weekly Worst Itch NRS</title>
          <description>Participants will be asked to complete a daily itch diary with their worst itch numeric rating scale (WI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Daily diary data were averaged weekly. The missing weekly data have been imputed by the mean WI-NRS value of each participant.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.1" spread="2.3"/>
                    <measurement group_id="O2" value="7.3" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="2.3"/>
                    <measurement group_id="O2" value="6.3" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.1" spread="2.0"/>
                    <measurement group_id="O2" value="5.9" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.5" spread="1.9"/>
                    <measurement group_id="O2" value="5.7" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="1.7"/>
                    <measurement group_id="O2" value="5.6" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="2.2"/>
                    <measurement group_id="O2" value="5.7" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="2.3"/>
                    <measurement group_id="O2" value="5.8" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="2.2"/>
                    <measurement group_id="O2" value="5.6" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="2.4"/>
                    <measurement group_id="O2" value="5.4" spread="2.1"/>
                  </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>
            <groups_desc>Analysis of change from baseline through week 8 including all time points. For this analysis, data were censored at the time of participant discontinuation.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.09</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.11</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.24</ci_lower_limit>
            <ci_upper_limit>0.02</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weekly AI-NRS</title>
        <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and week 1, 2, 3, 4, 5, 6, 7, and 8</time_frame>
        <population>Daily diary data were averaged weekly. The missing weekly data have been imputed by the mean AI-NRS value of each participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Weekly AI-NRS</title>
          <description>Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Daily diary data were averaged weekly. The missing weekly data have been imputed by the mean AI-NRS value of each participant.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="2.2"/>
                    <measurement group_id="O2" value="6.3" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="2.2"/>
                    <measurement group_id="O2" value="5.6" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="1.9"/>
                    <measurement group_id="O2" value="5.6" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="2.0"/>
                    <measurement group_id="O2" value="5.2" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="1.7"/>
                    <measurement group_id="O2" value="5.2" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="2.0"/>
                    <measurement group_id="O2" value="5.1" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="2.1"/>
                    <measurement group_id="O2" value="5.1" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="1.7"/>
                    <measurement group_id="O2" value="5.2" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="2.0"/>
                    <measurement group_id="O2" value="5.0" spread="2.7"/>
                  </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>
            <groups_desc>Analysis of change from baseline through week 8 including all time points. For this analysis, data were censored at the time of participant discontinuation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.16</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.19</ci_lower_limit>
            <ci_upper_limit>0.03</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change (PGIC)</title>
        <description>PGIC categorized as &quot;Very much better&quot;, &quot;Moderately better&quot;, &quot;A little better&quot;, &quot;No change&quot;, &quot;A little worse&quot;, &quot;Moderately worse&quot;, and &quot;Very much worse&quot;.</description>
        <time_frame>month 2</time_frame>
        <population>Participants who completed the month 2 assessment are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change (PGIC)</title>
          <description>PGIC categorized as &quot;Very much better&quot;, &quot;Moderately better&quot;, &quot;A little better&quot;, &quot;No change&quot;, &quot;A little worse&quot;, &quot;Moderately worse&quot;, and &quot;Very much worse&quot;.</description>
          <population>Participants who completed the month 2 assessment are included in the analysis.</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="12"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very much better</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderately better</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>A little better</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>A little worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderately worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Dressing/Bathing NRS</title>
        <description>Participants will be asked to complete a daily itch diary with their itch Numeric Rating Scale (NRS) during dressing/bathing. Score range: 0 to 10, higher scores mean more itching.</description>
        <time_frame>baseline and week 1, 2, 3, 4, 5, 6, 7, and 8</time_frame>
        <population>Daily diary data were averaged weekly. The missing weekly data have been imputed by the mean Dressing/Bathing-NRS value of each participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Dressing/Bathing NRS</title>
          <description>Participants will be asked to complete a daily itch diary with their itch Numeric Rating Scale (NRS) during dressing/bathing. Score range: 0 to 10, higher scores mean more itching.</description>
          <population>Daily diary data were averaged weekly. The missing weekly data have been imputed by the mean Dressing/Bathing-NRS value of each participant.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="2.6"/>
                    <measurement group_id="O2" value="6.8" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="2.3"/>
                    <measurement group_id="O2" value="5.7" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="2.1"/>
                    <measurement group_id="O2" value="6.0" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="2.5"/>
                    <measurement group_id="O2" value="5.4" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="2.7"/>
                    <measurement group_id="O2" value="5.1" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="2.6"/>
                    <measurement group_id="O2" value="5.5" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="2.7"/>
                    <measurement group_id="O2" value="5.5" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="2.8"/>
                    <measurement group_id="O2" value="5.4" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="2.7"/>
                    <measurement group_id="O2" value="5.4" spread="3.2"/>
                  </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>
            <groups_desc>Analysis of change from baseline through week 8 including all time points. For this analysis, data were censored at the time of participant discontinuation.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.002</p_value>
            <p_value_desc>A p-value of &lt;0.05 would be considered statistically significant.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.25</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.41</ci_lower_limit>
            <ci_upper_limit>-0.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Static Participant Assessment of Itch</title>
        <description>Severity of itch over past 7 days assessed as Very Severe, Severe, Moderate, Mild, or None.&#xD;
Change is reported as the number of participants with 3-category improvement, 2-category improvement, 1-category improvement, no change, or worse.</description>
        <time_frame>month 2</time_frame>
        <population>Participants who enrolled after protocol amendment adding this outcome measure are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Oral Tablet</title>
            <description>Patients undergo two months of dosing with placebo followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Serlopitant Tablet</title>
            <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients may continue in a 3-month open label extension with serlopitant at 5 mg (taken by mouth) daily for continued safety monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Static Participant Assessment of Itch</title>
          <description>Severity of itch over past 7 days assessed as Very Severe, Severe, Moderate, Mild, or None.&#xD;
Change is reported as the number of participants with 3-category improvement, 2-category improvement, 1-category improvement, no change, or worse.</description>
          <population>Participants who enrolled after protocol amendment adding this outcome measure are included in the analysis</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="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>3-category improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2-category improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1-category improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 15 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo Oral Tablet</title>
          <description>Patients undergo two months of dosing with a placebo followed by one month of wash-out. All patients were invited to participate in an open-label extension study.</description>
        </group>
        <group group_id="E2">
          <title>Serlopitant Tablet</title>
          <description>Patients who will undergo two months of Serlopitant dosing, followed by one month of wash-out. All patients were invited to participate in an open-label extension study.</description>
        </group>
        <group group_id="E3">
          <title>Open-label Extension</title>
          <description>Participants took oral serlopitant 5mg daily for either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020).</description>
        </group>
      </group_list>
      <serious_events>
        <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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Bacteremia (sepsis)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="9" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Enlarged lymph nodes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Worsening anemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Enlarged parotid gland</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Elevated leukocyte esterase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Type 2 diabetes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal abrasion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Soft stool</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cracked tooth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pruritus of pharynx</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Inflamed cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated ALT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Elevated GGT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Swollen cheek due to wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>The COVID-19 infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Elevated prolactin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Chronic headaches</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney stone surgery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Microscopic pyuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Irregular menstruation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vaginal discharge</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Maculopapular rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Irritant dermatitis around G-tube</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <limitations_and_caveats>The primary limitation of the study is the small sample size due to the rarity of EB, the COVID-19 pandemic-related disruptions, and limited drug availability.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Albert Chiou</name_or_title>
      <organization>Stanford University</organization>
      <phone>(650) 721-8418</phone>
      <email>achiou@stanford.edu</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/NCT03836001
org study id: 49084
nct id: NCT03836001
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
To determine if Serlopitant (when taken by mouth) is safe and works on itch in patients aged
      13 and above with EB.
The investigator will determine whether more patients taking serlopitant 5 mg daily as
      compared to placebo can achieve at least a 3-point reduction in the 24-hour Average Itch
      Numeric Rating Scale (NRS) following two months of treatment.

      Secondary objectives include;

        1. comparative weekly change in daily worst itch NRS,

        2. comparative weekly change in daily average itch NRS,

        3. the proportion of patients who achieve at least 30% or 50% reduction in Average Itch NRS
           at month 2,

        4. proportion of patients achieving 2-point and 4-point reductions in Average Itch NRS at
           month 2,

        5. Patient Global Impression of Change (PGIC) at month 2, the change in participant static
           assessment of itch at month 2, and

        6. assessment of the safety of serlopitant in adolescents (≥13 y.o.) and adults with
           epidermolysis bullosa-related itch.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is an investigator-initiated, single-center, randomized, double-blind, placebo-controlled, parallel-arm trial evaluating the effects of serlopitant at 5 mg by mouth daily on EB-related itch.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: This is a double-blind study.
measure: Number of Patients Who Achieve at Least a 3-point Reduction in AI-NRS.
time frame: baseline and after two months of treatment
description: Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Number of Patients Who Achieve at Least a 2-point Reduction in AI-NRS.
time frame: baseline and after two months of treatment
description: Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Number of Patients Who Achieve at Least a 4-point Reduction in AI-NRS.
time frame: baseline and after two months of treatment
description: Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Number of Patients Who Achieve at Least a 30% Reduction in AI-NRS.
time frame: baseline and after two months of treatment
description: Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Number of Patients Who Achieve at Least a 50% Reduction in AI-NRS.
time frame: baseline and after two months of treatment
description: Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Weekly Worst Itch NRS
time frame: baseline and week 1, 2, 3, 4, 5, 6, 7, and 8
description: Participants will be asked to complete a daily itch diary with their worst itch numeric rating scale (WI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Weekly AI-NRS
time frame: baseline and week 1, 2, 3, 4, 5, 6, 7, and 8
description: Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.
measure: Patient Global Impression of Change (PGIC)
time frame: month 2
description: PGIC categorized as "Very much better", "Moderately better", "A little better", "No change", "A little worse", "Moderately worse", and "Very much worse".
measure: Change in Static Participant Assessment of Itch
time frame: month 2
description: Severity of itch over past 7 days assessed as Very Severe, Severe, Moderate, Mild, or None.
Change is reported as the number of participants with 3-category improvement, 2-category improvement, 1-category improvement, no change, or worse.
arm group label: Placebo Oral Tablet
arm group type: Placebo Comparator
description: Participants will undergo two months of dosing with a placebo (inactive drug or sugar pill), followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.
arm group label: Serlopitant Tablet
arm group type: Active Comparator
description: Participants will undergo two months of Serlopitant 5mg daily per oral, followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.
intervention type: Drug
intervention name: Serlopitant Tablet
description: Serlopitant is a small molecule, highly selective NK1-R (neurokinin-1 receptor) antagonist. Two critical mediators of the urge to scratch are Substance P, or SP, and its receptor, NK1-R. SP is a naturally occurring peptide in the tachykinin neuropeptide family. Tachykinins have a broad range of functions in the nervous and immune systems. SP binding of NK1-R has been shown to be a key mediator of sensory nerve signaling, including the itch-scratch reflex and the vomiting reflex.
arm group label: Serlopitant Tablet
other name: VPD-737
intervention type: Drug
intervention name: Placebo Oral Tablet
description: The placebo is a tablet that looks like a drug but has no drug or other active ingredient in it.
arm group label: Placebo Oral Tablet
other name: Sugar pill
criteria: 
gender: All
minimum age: 13 Years
maximum age: N/A
healthy volunteers: No
last name: Albert S Chiou, MD/MBA
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Albert Chiou
investigator title: Assistant Professor of Dermatology.
mesh term: Epidermolysis Bullosa
mesh term: Pruritus
mesh term: Serlopitant
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The primary limitation of the study is the small sample size due to the rarity of EB, the COVID-19 pandemic-related disruptions, and limited drug availability.
point of contact: 