<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/NCT02246920</url>
  </required_header>
  <id_info>
    <org_study_id>71336007</org_study_id>
    <nct_id>NCT02246920</nct_id>
  </id_info>
  <brief_title>Clinical Equivalence Study of Fluticasone Propionate Nasal Spray, 50 mcg/Actuation vs. Flonase in Allergic Rhinitis Patients</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multi-Site Study to Compare the Therapeutic Equivalence of Fluticasone Propionate Nasal Spray, 50 mcg With Flonase® Nasal Spray in the Relief of the Signs and Symptoms of Seasonal Allergic Rhinitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Teva Pharmaceuticals USA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teva Pharmaceuticals USA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This double-blind, randomized, placebo-controlled, parallel group, multi-site study has been&#xD;
      designed to compare the safety and efficacy of a generic Fluticasone propionate Nasal Spray,&#xD;
      50 mcg (Teva Pharmaceuticals USA) to the FDA Reference Listed Drug, Flonase® (fluticasone&#xD;
      propionate) 50 mcg nasal spray (GlaxoSmithKline), in the relief of the signs and symptoms of&#xD;
      Seasonal Allergic Rhinitis. Additionally, both the test and reference formulations will be&#xD;
      tested for superiority against a placebo nasal spray.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Development Halted&#xD;
  </why_stopped>
  <start_date type="Actual">March 1, 2014</start_date>
  <completion_date type="Actual">July 14, 2014</completion_date>
  <primary_completion_date type="Actual">July 14, 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Average AM/PM Reflective Total Nasal Symptom Score (rTNSS) Over Days 1 to 14.</measure>
    <time_frame>2 week treatment period: Day 0-14</time_frame>
    <description>Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.&#xD;
The primary analysis for determining the therapeutic equivalence of the Test and Reference treatments will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.&#xD;
The Per-Protocol Population (PPP) will be used for the primary analysis of bioequivalence.&#xD;
The Modified Intent to Treat Population (mITT) will be used for Superiority Analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Average Instantaneous Total Nasal Symptom Score (iTNSS) Over Days 1 to 14.</measure>
    <time_frame>2 week treatment period: Day 0 to Day 14</time_frame>
    <description>Secondary efficacy analysis will evaluate the mean change from baseline in average iTNSS over the 2 week randomization treatment period.&#xD;
The Per-Protocol Population (PPP) will be used for the analysis of bioequivalence.&#xD;
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Superiority to Placebo</measure>
    <time_frame>2 week treatment period: Day 0 to Day 14</time_frame>
    <description>The primary analysis for determining the superiority of each active treatment over placebo will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.&#xD;
The modified Intent-to-Treat Population (mITT) will be used for the primary analysis of superiority.&#xD;
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1474</enrollment>
  <condition>Seasonal Allergic Rhinitis</condition>
  <arm_group>
    <arm_group_label>Investigational Test Product</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference Listed Drug</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone propionate</intervention_name>
    <description>50 mcg/actuation Nasal Spray</description>
    <arm_group_label>Investigational Test Product</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Flonase®</intervention_name>
    <description>50 mcg/actuation Nasal Spray</description>
    <arm_group_label>Reference Listed Drug</arm_group_label>
    <other_name>Fluticasone propionate (generic name)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive Nasal Spray</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or non-pregnant, non-lactating female 12 years or age or older.&#xD;
&#xD;
          -  Signed informed consent form, which meets all criteria of current FDA regulations. For&#xD;
             patients under the age of majority in the state the study is being conducted (18 years&#xD;
             in most states) the parent or legal guardian should sign the consent form and the&#xD;
             child will be required to sign a patient &quot;assent&quot; form that will be written in such a&#xD;
             way as to be understandable to a child.&#xD;
&#xD;
          -  If female and of child-bearing potential, have a negative urine pregnancy test and is&#xD;
             prepared to abstain from sexual intercourse or use a reliable method of contraception&#xD;
             during the study. In order for hormonal birth control to be considered a reliable&#xD;
             method the patient must have been on their regimen for at least 28 days.&#xD;
&#xD;
          -  Documented positive allergic skin test, performed within the previous 12 months, to&#xD;
             one or more of the allergens in season at the time the study is being conducted.&#xD;
&#xD;
          -  A minimum of two consecutive years of previous history of seasonal allergic rhinitis&#xD;
             to the pollen/allergen in season at the time the study is being conducted.&#xD;
&#xD;
          -  A score of at least 6 on the reflective Total Nasal Symptom Score (rTNSS) and a&#xD;
             minimum score of at least 2 for &quot;nasal congestion&quot; and a minimum score of at least 2&#xD;
             for one of the remaining 3 symptoms representing the 12 hours prior to the screening&#xD;
             visit.&#xD;
&#xD;
          -  An average composite score of at least 6 on the reflective Total Nasal Symptom Score&#xD;
             (rTNSS) and a minimum score of at least 2 for &quot;nasal congestion&quot; and a minimum score&#xD;
             of at least 2 for one of the remaining 3 symptoms representing the last 3 days of the&#xD;
             7-day lead-in period before the randomization visit and the morning of the first day&#xD;
             of the randomization visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Under 12 years of age.&#xD;
&#xD;
          -  Females who are pregnant, lactating, or likely to become pregnant during the study.&#xD;
&#xD;
          -  Negative or lack of documented skin allergen test (performed within the previous 12&#xD;
             months) to at least one of the allergens in season at the time of the study is being&#xD;
             conducted. The results of all positive shin allergen tests should be reported.&#xD;
&#xD;
          -  Patients who suffer from chronic signs and symptoms of perennial allergic rhinitis&#xD;
             (PAR) should be excluded from the study unless the Investigator assesses that the&#xD;
             patient's current signs and symptoms are a clear exacerbation of Seasonal Allergic&#xD;
             Rhinitis (SAR) rather than chronic PAR.&#xD;
&#xD;
          -  Patients who suffer only from perennial allergic rhinitis or seasonal allergic&#xD;
             rhinitis to a different allergen that that in season at the time the study is&#xD;
             conducted.&#xD;
&#xD;
          -  Previous history of less than 2 years of seasonal allergic rhinitis to the&#xD;
             pollen/allergen in season at the time the study is being conducted.&#xD;
&#xD;
          -  A total score of less that 6 on the reflective Total Nasal Symptom Score (rTNSS) or a&#xD;
             score of less than 2 for &quot;nasal congestion&quot; or a score of less than 2 for all 3 of the&#xD;
             remaining symptoms.&#xD;
&#xD;
          -  History of asthma over the previous 2 years that required chronic therapy. Occasional&#xD;
             acute or mild exercise induced asthma will be allowable on the condition that the&#xD;
             treatment of the attacks is restricted to beta-agonists only.&#xD;
&#xD;
          -  Patients with nasal conditions, including infectious rhinitis, rhinitis medicamentosa,&#xD;
             or atrophic rhinitis.&#xD;
&#xD;
          -  Clinically significant nasal deformity (e.g. significantly deformed septum, nasal&#xD;
             polyps, or ulcers) or any recent nasal surgery or trauma that has not completely&#xD;
             healed.&#xD;
&#xD;
          -  Sinus infection within the previous 30 days or history of re-occuring sinus&#xD;
             infections.&#xD;
&#xD;
          -  Patient has started immunotherapy (including topical or desensitization therapy) or&#xD;
             changed their dose of immunotherapy within 30 days of the first dose, or is likely to&#xD;
             have to start immunotherapy, or change their current dose during the study.&#xD;
&#xD;
          -  Treatment for oral Candidiasis within 30 days of starting the study or a current&#xD;
             Candidiasis infection.&#xD;
&#xD;
          -  Upper respiratory tract infection within the previous 30 days.&#xD;
&#xD;
          -  Patients with a history of tuberculosis.&#xD;
&#xD;
          -  Patients with the presence of glaucoma, cataracts, ocular herpes simplex,&#xD;
             conjunctivitis, or other eye infection not related to the diagnosis of SAR within 14&#xD;
             days of enrollment.&#xD;
&#xD;
          -  The patient has had recent exposure (30 days) or was at risk of being exposed to&#xD;
             chicken pox or measles.&#xD;
&#xD;
          -  Patients with any untreated fungal, bacterial, or systemic viral infections within the&#xD;
             previous 30 days.&#xD;
&#xD;
          -  Use of any ophthalmic steroids within 14 days or nasal, inhaled, or systemic steroids&#xD;
             within 30 days of the study start.&#xD;
&#xD;
          -  Use of medications that significantly inhibit the cytochrome P450 subfamily enzyme&#xD;
             CYP3A4.&#xD;
&#xD;
          -  Use of intranasal or systemic second-generation anti-histamines within 10 days of&#xD;
             enrollment.&#xD;
&#xD;
          -  Use of intranasal cromolyn within 14 days of enrollment.&#xD;
&#xD;
          -  Use of intranasal or systemic first-generation anti-histamines, leukotriene receptor&#xD;
             antagonists or other nasal decongestants within 3 days of enrollment.&#xD;
&#xD;
          -  Use of any tricyclic anti-depressant within 30 days of enrollment.&#xD;
&#xD;
          -  Patients with attention-deficit disorder being treated with methylphenidate containing&#xD;
             products that have not been on a stable dosing regimen for at least the 30 previous&#xD;
             days and who cannot remain on the same dosing regimen throughout the study.&#xD;
&#xD;
          -  Desensitization therapy to the seasonal allergen that is causing the patients allergic&#xD;
             rhinitis within the previous 6 months.&#xD;
&#xD;
          -  Previous SAR and/or PAR that has proven unresponsive to steroid therapy.&#xD;
&#xD;
          -  Any known hypersensitivity to fluticasone, other steroids, or any of the components of&#xD;
             the study nasal sprays.&#xD;
&#xD;
          -  Significant history or current evidence of chronic infectious disease, system&#xD;
             disorder, organ disorder, or other medical condition that in the Investigator's&#xD;
             opinion would place the study patient at undue risk by participating, or could&#xD;
             jeopardize the integrity of the study evaluations.&#xD;
&#xD;
          -  Receipt of any drug as part of a research study within 30 days prior to the first&#xD;
             dose.&#xD;
&#xD;
          -  Planned travel outside of the local area for more than 2 consecutive days or 3 days in&#xD;
             total, during the patient's participation in the study.&#xD;
&#xD;
          -  Previous participation in this study.&#xD;
&#xD;
          -  The patient has a history or non-compliance with medical regimens or treatment&#xD;
             protocols in previous clinical studies.&#xD;
&#xD;
          -  The patient is a member of the investigational study staff or a member of the family&#xD;
             of the investigational study staff.&#xD;
&#xD;
          -  The patient currently smokes cigarettes, cigars, and/or pipes and is a heavy smoker&#xD;
             (for example, on average more than 10 cigarettes per day).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novum Pharmaceutical Research Services</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <results_first_submitted>October 6, 2020</results_first_submitted>
  <results_first_submitted_qc>May 11, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 8, 2023</results_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bioequivalence</keyword>
  <keyword>Allergic Rhinitis</keyword>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>1474 subjects with SAR were enrolled into placebo run-in for the study.</recruitment_details>
      <pre_assignment_details>Subjects were required to enter a 7 day placebo phase prior to randomization. 296 subjects were discovered to be placebo responders and were discontinued from the trial.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Investigational Test Product</title>
          <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
        </group>
        <group group_id="P2">
          <title>Reference Listed Drug</title>
          <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="484"/>
                <participants group_id="P2" count="460"/>
                <participants group_id="P3" count="234"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="477"/>
                <participants group_id="P2" count="453"/>
                <participants group_id="P3" count="231"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" 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 group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Population Randomized.</population>
      <group_list>
        <group group_id="B1">
          <title>Investigational Test Product</title>
          <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
        </group>
        <group group_id="B2">
          <title>Reference Listed Drug</title>
          <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="484"/>
            <count group_id="B2" value="460"/>
            <count group_id="B3" value="234"/>
            <count group_id="B4" value="1178"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.3" lower_limit="12" upper_limit="80"/>
                    <measurement group_id="B2" value="39.4" lower_limit="12" upper_limit="76"/>
                    <measurement group_id="B3" value="39.1" lower_limit="12" upper_limit="77"/>
                    <measurement group_id="B4" value="39.3" lower_limit="12" upper_limit="80"/>
                  </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="292"/>
                    <measurement group_id="B2" value="274"/>
                    <measurement group_id="B3" value="154"/>
                    <measurement group_id="B4" value="720"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="192"/>
                    <measurement group_id="B2" value="186"/>
                    <measurement group_id="B3" value="80"/>
                    <measurement group_id="B4" value="458"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="114"/>
                    <measurement group_id="B2" value="108"/>
                    <measurement group_id="B3" value="64"/>
                    <measurement group_id="B4" value="286"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="357"/>
                    <measurement group_id="B2" value="339"/>
                    <measurement group_id="B3" value="160"/>
                    <measurement group_id="B4" value="856"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Average AM/PM Reflective Total Nasal Symptom Score (rTNSS) Over Days 1 to 14.</title>
        <description>Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.&#xD;
The primary analysis for determining the therapeutic equivalence of the Test and Reference treatments will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.&#xD;
The Per-Protocol Population (PPP) will be used for the primary analysis of bioequivalence.&#xD;
The Modified Intent to Treat Population (mITT) will be used for Superiority Analysis.</description>
        <time_frame>2 week treatment period: Day 0-14</time_frame>
        <population>Per Protocol Population</population>
        <group_list>
          <group group_id="O1">
            <title>Investigational Test Product</title>
            <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Reference Listed Drug</title>
            <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Average AM/PM Reflective Total Nasal Symptom Score (rTNSS) Over Days 1 to 14.</title>
          <description>Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.&#xD;
The primary analysis for determining the therapeutic equivalence of the Test and Reference treatments will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.&#xD;
The Per-Protocol Population (PPP) will be used for the primary analysis of bioequivalence.&#xD;
The Modified Intent to Treat Population (mITT) will be used for Superiority Analysis.</description>
          <population>Per Protocol Population</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="479"/>
                <count group_id="O2" value="458"/>
                <count group_id="O3" value="233"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.77" spread="0.11"/>
                    <measurement group_id="O2" value="-1.57" spread="0.10"/>
                    <measurement group_id="O3" value="-1.26" spread="0.15"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Equivalence is established if the 90% confidence interval is contained within 80.00-125.00%.</non_inferiority_desc>
            <param_type>T/R Ls Mean Ratio</param_type>
            <param_value>108.09</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>94.09</ci_lower_limit>
            <ci_upper_limit>124.40</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Average Instantaneous Total Nasal Symptom Score (iTNSS) Over Days 1 to 14.</title>
        <description>Secondary efficacy analysis will evaluate the mean change from baseline in average iTNSS over the 2 week randomization treatment period.&#xD;
The Per-Protocol Population (PPP) will be used for the analysis of bioequivalence.&#xD;
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.</description>
        <time_frame>2 week treatment period: Day 0 to Day 14</time_frame>
        <population>Per Protocol Population</population>
        <group_list>
          <group group_id="O1">
            <title>Investigational Test Product</title>
            <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Reference Listed Drug</title>
            <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Average Instantaneous Total Nasal Symptom Score (iTNSS) Over Days 1 to 14.</title>
          <description>Secondary efficacy analysis will evaluate the mean change from baseline in average iTNSS over the 2 week randomization treatment period.&#xD;
The Per-Protocol Population (PPP) will be used for the analysis of bioequivalence.&#xD;
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.</description>
          <population>Per Protocol Population</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="479"/>
                <count group_id="O2" value="458"/>
                <count group_id="O3" value="233"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.70" spread="0.11"/>
                    <measurement group_id="O2" value="-1.53" spread="0.11"/>
                    <measurement group_id="O3" value="-1.15" spread="0.15"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Equivalence is demonstrated when the 90% confidence interval is contained within 80.00-125.00%.</non_inferiority_desc>
            <param_type>T/R LS Mean Ratio</param_type>
            <param_value>107.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>92.42</ci_lower_limit>
            <ci_upper_limit>124.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Superiority to Placebo</title>
        <description>The primary analysis for determining the superiority of each active treatment over placebo will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.&#xD;
The modified Intent-to-Treat Population (mITT) will be used for the primary analysis of superiority.&#xD;
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.</description>
        <time_frame>2 week treatment period: Day 0 to Day 14</time_frame>
        <population>Modified Intent to Treat</population>
        <group_list>
          <group group_id="O1">
            <title>Investigational Test Product</title>
            <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Reference Listed Drug</title>
            <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Superiority to Placebo</title>
          <description>The primary analysis for determining the superiority of each active treatment over placebo will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.&#xD;
The modified Intent-to-Treat Population (mITT) will be used for the primary analysis of superiority.&#xD;
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.</description>
          <population>Modified Intent to Treat</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="479"/>
                <count group_id="O2" value="458"/>
                <count group_id="O3" value="233"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.77" spread="0.11"/>
                    <measurement group_id="O2" value="-1.57" spread="0.10"/>
                    <measurement group_id="O3" value="-1.26" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0028</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0169</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected from the time of ICF signature through the end of the study. Total duration 4-6 weeks</time_frame>
      <desc>Subjects were queried on health status and any changes at each visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>Investigational Test Product</title>
          <description>Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
        </group>
        <group group_id="E2">
          <title>Reference Listed Drug</title>
          <description>Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Saline Placebo Nasal Spray; 4 total sprays/day for 14 days</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.0)</default_vocab>
        <default_assessment>Non-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="484"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="234"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="484"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="234"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="484"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="234"/>
              </event>
              <event>
                <sub_title>Rib Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="484"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="234"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Conversion disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="484"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="234"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="484"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="234"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="484"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="460"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="234"/>
              </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>PI may not publish the results of this generic (ANDA) trial without sponsor review and approval.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, PD/CE Studies</name_or_title>
      <organization>Teva Pharmaceuticals USA</organization>
      <phone>1-888-483-8279</phone>
      <email>usmedinfo@tevapharm.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/NCT02246920
org study id: 71336007
nct id: NCT02246920
lead sponsor: 
has dmc: No
This double-blind, randomized, placebo-controlled, parallel group, multi-site study has been
      designed to compare the safety and efficacy of a generic Fluticasone propionate Nasal Spray,
      50 mcg (Teva Pharmaceuticals USA) to the FDA Reference Listed Drug, Flonase® (fluticasone
      propionate) 50 mcg nasal spray (GlaxoSmithKline), in the relief of the signs and symptoms of
      Seasonal Allergic Rhinitis. Additionally, both the test and reference formulations will be
      tested for superiority against a placebo nasal spray.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Average AM/PM Reflective Total Nasal Symptom Score (rTNSS) Over Days 1 to 14.
time frame: 2 week treatment period: Day 0-14
description: Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.
The primary analysis for determining the therapeutic equivalence of the Test and Reference treatments will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.
The Per-Protocol Population (PPP) will be used for the primary analysis of bioequivalence.
The Modified Intent to Treat Population (mITT) will be used for Superiority Analysis.
measure: Change From Baseline in Average Instantaneous Total Nasal Symptom Score (iTNSS) Over Days 1 to 14.
time frame: 2 week treatment period: Day 0 to Day 14
description: Secondary efficacy analysis will evaluate the mean change from baseline in average iTNSS over the 2 week randomization treatment period.
The Per-Protocol Population (PPP) will be used for the analysis of bioequivalence.
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.
measure: Superiority to Placebo
time frame: 2 week treatment period: Day 0 to Day 14
description: The primary analysis for determining the superiority of each active treatment over placebo will be based on each treatment's mean change from baseline for average rTNSS over the 2 week randomization treatment period.
The modified Intent-to-Treat Population (mITT) will be used for the primary analysis of superiority.
Total Nasal Symptom Score (TNSS) is defined as the sum of the patient-rated nasal symptom severity scores for the following four allergy symptoms: Runny Nose, Nasal Congestion, Itchy Nose, and Sneezing. The severity score for each symptom will be based on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The higher the score, the worse the symptoms of the 4 allergy categories are (runny nose, nasal congestions, itchy nose, and sneezing.
arm group label: Investigational Test Product
arm group type: Experimental
description: Fluticasone propionate Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days
arm group label: Reference Listed Drug
arm group type: Active Comparator
description: Flonase® (fluticasone propionate) Nasal Spray, 50 mcg/actuation; 200 mcg/day for 14 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Saline Placebo Nasal Spray; 4 total sprays/day for 14 days
intervention type: Drug
intervention name: Fluticasone propionate
description: 50 mcg/actuation Nasal Spray
arm group label: Investigational Test Product
intervention type: Drug
intervention name: Flonase®
description: 50 mcg/actuation Nasal Spray
arm group label: Reference Listed Drug
other name: Fluticasone propionate (generic name)
intervention type: Drug
intervention name: Placebo
description: Inactive Nasal Spray
arm group label: Placebo
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
mesh term: Rhinitis, Allergic, Seasonal
mesh term: Fluticasone
mesh term: Xhance
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 