<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/NCT02256553</url>
  </required_header>
  <id_info>
    <org_study_id>P08607</org_study_id>
    <nct_id>NCT02256553</nct_id>
  </id_info>
  <brief_title>Safety Study of MK-3641 and MK-7243 Co-administered in Adult Participants With Ragweed and Grass Pollen Induced Allergic Rhinitis (P08607, MK-3641-006)</brief_title>
  <official_title>A Phase IV, Open-label, Safety and Tolerability Trial of MK-3641 and MK-7243 Coadministered in Subjects At Least 18 Years of Age With Ragweed and Grass Pollen Induced Allergic Rhinitis With or Without Conjunctivitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ALK-Abelló A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ALK-Abelló A/S</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety and tolerability of MK-3641 (short ragweed&#xD;
      [Ambrosia artemisiifolia] extract, SCH 039641, RAGWITEK®) sublingual tablets and MK-7243&#xD;
      (Timothy grass [Phleum pratense] extract, SCH 697243, GRASTEK®) sublingual tablets&#xD;
      co-administered in participants 18 through 65 years of age with both ragweed- and grass&#xD;
      polled-induced allergic rhinitis, with or without conjunctivitis and with or without asthma.&#xD;
      The primary endpoint is the percentage of participants who experience at least one event of&#xD;
      local swelling after co-administration of MK-3641 and MK-7243 sublingual tablets.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Events of local swelling include pharyngeal edema, laryngeal edema, mouth edema,&#xD;
      oropharyngeal swelling, palatal edema, tongue swelling/edema or throat tightness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Who Experienced at Least One Event of Local Swelling</measure>
    <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
    <description>Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction</measure>
    <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
    <description>Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)</measure>
    <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
    <description>An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment</measure>
    <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
    <description>Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">102</enrollment>
  <condition>Rhinitis, Allergic, Seasonal</condition>
  <arm_group>
    <arm_group_label>MK-3641+ MK-7243</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MK-3641 12 Amb a 1-U (short ragweed extract)</intervention_name>
    <description>12 units of Ambrosia artemisiifolia major allergen number 1 (Amb a 1-U) extract sublingual tablets</description>
    <arm_group_label>MK-3641+ MK-7243</arm_group_label>
    <other_name>SCH 039641</other_name>
    <other_name>RAGWITEK®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MK-7243 2800 BAU (Timothy grass extract)</intervention_name>
    <description>2800 bioequivalent allergen units (BAU) of Phleum pratense extract sublingual tablets</description>
    <arm_group_label>MK-3641+ MK-7243</arm_group_label>
    <other_name>SCH 697243</other_name>
    <other_name>GRASTEK®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rescue Medication</intervention_name>
    <description>Self-injectable epinephrine, to be administered for an anaphylactic reaction, including symptoms/signs of upper airway obstruction.</description>
    <arm_group_label>MK-3641+ MK-7243</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical history of physician-diagnosed ragweed- and grass pollen-induced rhinitis&#xD;
             with or without conjunctivitis of &gt;1 year duration, with or without asthma&#xD;
&#xD;
          -  Female participants of childbearing potential must have a negative urine pregnancy&#xD;
             test at Screening and Randomization Visits and must agree to remain abstinent or use&#xD;
             (or have their partner use) any one of the acceptable methods of birth control within&#xD;
             the projected duration of the study. Acceptable methods of birth control are:&#xD;
             intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom,&#xD;
             vasectomy, hormonal contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstable, uncontrolled or severe asthma treated with long-acting beta agonists (LABAs)&#xD;
             at the time of Screening&#xD;
&#xD;
          -  Received immunosuppressive treatment within 3 months prior to Randomization (except&#xD;
             steroids for allergic reactions other than asthma)&#xD;
&#xD;
          -  History of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy,&#xD;
             unknown cause, or inhalant allergen&#xD;
&#xD;
          -  Diagnosis of eosinophilic esophagitis&#xD;
&#xD;
          -  History of any severe systemic allergic reaction or any severe local reaction to&#xD;
             sublingual allergen immunotherapy&#xD;
&#xD;
          -  Female and breastfeeding, pregnant or intending to become pregnant&#xD;
&#xD;
          -  Received another form of allergen immunotherapy with the past month&#xD;
&#xD;
          -  Previously exposed to MK-3641 (RAGWITEK®) or other sublingual ragweed immunotherapy&#xD;
&#xD;
          -  Previously exposed to MK-7243 (GRASTEK®) or other sublingual grass immunotherapy&#xD;
&#xD;
          -  Known history of allergy, hypersensitivity, or intolerance to the excipient&#xD;
             ingredients of the study drug (except for Ambrosia artemisiifolia and/or Phleum&#xD;
             pratense), or self-injectable epinephrine&#xD;
&#xD;
          -  Unable to or will not comply with the use of self-injectable epinephrine&#xD;
&#xD;
          -  Used an investigational drug within 30 days prior to Screening Visit, or plans to&#xD;
             participate in another interventional clinical trial during the duration of this trial&#xD;
&#xD;
          -  Family member of the investigational or sponsor staff involved in this trial&#xD;
&#xD;
          -  Participating in this same trial at another investigational site.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Canada</country>
    <country>United States</country>
  </removed_countries>
  <results_reference>
    <citation>Maloney J, Berman G, Gagnon R, Bernstein DI, Nelson HS, Kleine-Tebbe J, Kaur A, Li Q, Nolte H. Sequential Treatment Initiation with Timothy Grass and Ragweed Sublingual Immunotherapy Tablets Followed by Simultaneous Treatment Is Well Tolerated. J Allergy Clin Immunol Pract. 2016 Mar-Apr;4(2):301-9.e2. doi: 10.1016/j.jaip.2015.11.004. Epub 2016 Jan 2.</citation>
    <PMID>26755098</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <results_first_submitted>December 7, 2015</results_first_submitted>
  <results_first_submitted_qc>December 7, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 18, 2016</results_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhinitis</mesh_term>
    <mesh_term>Rhinitis, Allergic</mesh_term>
    <mesh_term>Rhinitis, Allergic, Seasonal</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>MK-3641+MK-7243</title>
          <description>Participants receive one MK-7243 tablet, sublingually (SL) once a day (QD) in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period I</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="102"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period II</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="94"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject Moved</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period III</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="94"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="91"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>MK-3641+MK-7243</title>
          <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="102"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.0" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Experienced at Least One Event of Local Swelling</title>
        <description>Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
        <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
        <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-3641+MK-7243</title>
            <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced at Least One Event of Local Swelling</title>
          <description>Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
          <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Period I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.7" lower_limit="7.7" upper_limit="22.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.6" lower_limit="14.0" upper_limit="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.7" lower_limit="8.5" upper_limit="23.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction</title>
        <description>Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
        <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
        <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-3641+MK-7243</title>
            <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction</title>
          <description>Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
          <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Period I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.6" lower_limit="60.7" upper_limit="79.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.6" lower_limit="58.7" upper_limit="77.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.9" lower_limit="45.7" upper_limit="65.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)</title>
        <description>An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE.</description>
        <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
        <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-3641+MK-7243</title>
            <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)</title>
          <description>An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE.</description>
          <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Period I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" lower_limit="1.6" upper_limit="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.0" upper_limit="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" lower_limit="0.6" upper_limit="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment</title>
        <description>Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
        <time_frame>During Period I, Period II and Period III (Up to 6 weeks)</time_frame>
        <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>MK-3641+MK-7243</title>
            <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment</title>
          <description>Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.</description>
          <population>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Period I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" lower_limit="1.6" upper_limit="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" lower_limit="1.1" upper_limit="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Period III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.0" upper_limit="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 8 weeks</time_frame>
      <desc>All Treated Participants population consisted of all participants who received ≥1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Period I: MK-7243</title>
          <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
        </group>
        <group group_id="E2">
          <title>Period II: MK-3641+MK-7243</title>
          <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
        </group>
        <group group_id="E3">
          <title>Period III: MK-3641+MK-7243</title>
          <description>Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="94"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="102"/>
                <counts group_id="E2" subjects_affected="68" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="55" subjects_at_risk="94"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pruritus</sub_title>
                <counts group_id="E1" events="66" subjects_affected="34" subjects_at_risk="102"/>
                <counts group_id="E2" events="68" subjects_affected="33" subjects_at_risk="96"/>
                <counts group_id="E3" events="38" subjects_affected="20" subjects_at_risk="94"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="102"/>
                <counts group_id="E2" events="21" subjects_affected="11" subjects_at_risk="96"/>
                <counts group_id="E3" events="10" subjects_affected="6" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Glossodynia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="102"/>
                <counts group_id="E2" events="13" subjects_affected="9" subjects_at_risk="96"/>
                <counts group_id="E3" events="13" subjects_affected="7" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Lip swelling</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="102"/>
                <counts group_id="E2" events="19" subjects_affected="14" subjects_at_risk="96"/>
                <counts group_id="E3" events="13" subjects_affected="10" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="102"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" events="19" subjects_affected="8" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Oedema mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" events="11" subjects_affected="6" subjects_at_risk="96"/>
                <counts group_id="E3" events="15" subjects_affected="9" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Oral pruritus</sub_title>
                <counts group_id="E1" events="95" subjects_affected="51" subjects_at_risk="102"/>
                <counts group_id="E2" events="109" subjects_affected="46" subjects_at_risk="96"/>
                <counts group_id="E3" events="54" subjects_affected="33" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Palatal oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Paraesthesia oral</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="102"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Swollen tongue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" events="13" subjects_affected="10" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Tongue ulceration</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="102"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pharyngeal oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E2" events="12" subjects_affected="9" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="102"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="94"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" events="93" subjects_affected="54" subjects_at_risk="102"/>
                <counts group_id="E2" events="99" subjects_affected="45" subjects_at_risk="96"/>
                <counts group_id="E3" events="46" subjects_affected="29" subjects_at_risk="94"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 45 days prior to submission for publication/presentation.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02256553
org study id: P08607
nct id: NCT02256553
lead sponsor: 
has dmc: No
The purpose of this study is to assess the safety and tolerability of MK-3641 (short ragweed
      [Ambrosia artemisiifolia] extract, SCH 039641, RAGWITEK®) sublingual tablets and MK-7243
      (Timothy grass [Phleum pratense] extract, SCH 697243, GRASTEK®) sublingual tablets
      co-administered in participants 18 through 65 years of age with both ragweed- and grass
      polled-induced allergic rhinitis, with or without conjunctivitis and with or without asthma.
      The primary endpoint is the percentage of participants who experience at least one event of
      local swelling after co-administration of MK-3641 and MK-7243 sublingual tablets.
Events of local swelling include pharyngeal edema, laryngeal edema, mouth edema,
      oropharyngeal swelling, palatal edema, tongue swelling/edema or throat tightness.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Who Experienced at Least One Event of Local Swelling
time frame: During Period I, Period II and Period III (Up to 6 weeks)
description: Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.
measure: Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction
time frame: During Period I, Period II and Period III (Up to 6 weeks)
description: Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
time frame: During Period I, Period II and Period III (Up to 6 weeks)
description: An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE.
measure: Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment
time frame: During Period I, Period II and Period III (Up to 6 weeks)
description: Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.
arm group label: MK-3641+ MK-7243
arm group type: Experimental
description: Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
intervention type: Biological
intervention name: MK-3641 12 Amb a 1-U (short ragweed extract)
description: 12 units of Ambrosia artemisiifolia major allergen number 1 (Amb a 1-U) extract sublingual tablets
arm group label: MK-3641+ MK-7243
other name: SCH 039641
other name: RAGWITEK®
intervention type: Biological
intervention name: MK-7243 2800 BAU (Timothy grass extract)
description: 2800 bioequivalent allergen units (BAU) of Phleum pratense extract sublingual tablets
arm group label: MK-3641+ MK-7243
other name: SCH 697243
other name: GRASTEK®
intervention type: Drug
intervention name: Rescue Medication
description: Self-injectable epinephrine, to be administered for an anaphylactic reaction, including symptoms/signs of upper airway obstruction.
arm group label: MK-3641+ MK-7243
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Canada
country: United States
citation: Maloney J, Berman G, Gagnon R, Bernstein DI, Nelson HS, Kleine-Tebbe J, Kaur A, Li Q, Nolte H. Sequential Treatment Initiation with Timothy Grass and Ragweed Sublingual Immunotherapy Tablets Followed by Simultaneous Treatment Is Well Tolerated. J Allergy Clin Immunol Pract. 2016 Mar-Apr;4(2):301-9.e2. doi: 10.1016/j.jaip.2015.11.004. Epub 2016 Jan 2.
PMID: 26755098
responsible party type: Sponsor
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
mesh term: Rhinitis, Allergic, Seasonal
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 