<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/NCT02238353</url>
  </required_header>
  <id_info>
    <org_study_id>azelastine/fluticasone AZE/FLU</org_study_id>
    <nct_id>NCT02238353</nct_id>
  </id_info>
  <brief_title>AZELASTINE/FLUTICASONE (AZE/FLU) Nasal Spray on Symptom Control, Nasal Mediators and Nasal Hyperresponsiveness in Allergic Rhinitis (AR)</brief_title>
  <official_title>AZE/FLU Nasal Spray on Symptom Control, Nasal Mediators and Nasal Hyperresponsiveness in Allergic Rhinitis (AR)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Comparative analysis of the efficacy of intranasal MP29-02 (a novel formulation of azelastine&#xD;
      and FP) has already been conducted in patients with moderate-to-severe seasonal AR. The&#xD;
      combination formulation appeared to be superior in these patients with better symptomatic&#xD;
      relief. However, objective analysis of the effect of this treatment on nasal mediators and/or&#xD;
      nasal hyperreactivity has not yet been performed and would help in understanding the&#xD;
      additional benefit of the combination treatment over monotherapy with nasal corticosteroids.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Comparative analysis of the efficacy of intranasal MP29-02 (a novel formulation of azelastine&#xD;
      and FP) has already been conducted in patients with moderate-to-severe seasonal AR. The&#xD;
      combination formulation appeared to be superior in these patients with better symptomatic&#xD;
      relief. However, objective analysis of the effect of this treatment on nasal mediators and/or&#xD;
      nasal hyperreactivity has not yet been performed and would help in understanding the&#xD;
      additional benefit of the combination treatment over monotherapy with nasal corticosteroids.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in expression of inflammatory mediators (Histamine / Substance P / IL-5 / EPO)</measure>
    <time_frame>4 weeks after treatment</time_frame>
    <description>Change in expression of inflammatory mediators (Histamine / Substance P / interleukin 5 (IL-5) / EPO) at after 4 weeks of therapy with AZE/FP or placebo nasal spray.&#xD;
Unit of measurement: µg/ml</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in PNIF values upon CDA exposure</measure>
    <time_frame>4 weeks treatment</time_frame>
    <description>Nasal hyperreactivity (NHR) can be assessed with peak nasal inspiratory flow (PNIF) measurement before and after cold dry air (CDA) provocation.&#xD;
Peak nasal inspiratory flow (PNIF) Peak nasal inspiratory flow evaluation is a physiologic measure of air flow through both nasal cavities during forced inspiration. The PNIF can be measured using a portable nasal inspiratory ﬂow meter and is expressed in liters per minute.&#xD;
Cold dry air (CDA) provocation CDA nasal provocation can be performed by delivering compressed dry air through a mask placed over nose and mouth of the patient, while breathing only through the nose. Patients will be exposed during 15 minutes. NHR is defined as a drop in PNIF larger than 20 % from baseline upon CDA challenge.&#xD;
The efficacy of MP29-02 treatment will be evaluated by measuring the change in PNIF values upon CDA exposure in both treatment arms.&#xD;
Unit of measurement of PNIF: L/min</description>
  </secondary_outcome>
  <other_outcome>
    <measure>change in assessment of visual analogue scale (VAS) for total nasal symptom (TNS) and individual nasal symptoms, reflective total of 5 symptom scores (rT5SS) and Allergic Rhinitis Control Test (ARCT)</measure>
    <time_frame>1 week after treatment</time_frame>
    <description>A Visual Analogue Scale (VAS) is a measurement of patient's subjective evaluation of symptom severity. Patients will score the severity of their total nasal symptoms (TNS) on a scale, as well as each individual nasal symptom (rhinorrhea, pruritis, sneezing, nasal obstruction), with 0 meaning no symptoms and 10 meaning the worst symptoms. The cut off value of 5/10 is to distinguish between controlled and uncontrolled AR.&#xD;
Patients will score their reflective nasal and ocular symptoms on a 4-point scale from absent (0), mild (1), moderate (2) to severe (3)). Minimum score: 0/15 as having no trouble with any of the symptoms; and maximum score: 15/15 as having maximum trouble with all the symptoms&#xD;
The Allergic Rhinitis Control Test (ARCT): Patients score the five questions from 1 (always troublesome) to 5 (never troublesome). Minimum score: 5/25 ; maximum score: 25/25. A score from 5/25 to 20/25 is assumed not controlled AR; a score higher then 20/25 is assumed controlled.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effects of therapy with AZE/FP or placebo on nasal inflammatory mediators (Histamine / Substance P (SP) / IL-5 / EPO)</measure>
    <time_frame>one week after treatment</time_frame>
    <description>Change in expression of inflammatory mediators (Histamine / Substance P / IL-5 / EPO) at after 1 week of therapy with AZE/FP or placebo nasal spray.&#xD;
Unit of measurement: µg/ml</description>
  </other_outcome>
  <other_outcome>
    <measure>change in PNIF values upon CDA exposure</measure>
    <time_frame>1 week of treatment</time_frame>
    <description>Nasal hyperreactivity (NHR) can be assessed with peak nasal inspiratory flow (PNIF) measurement before and after cold dry air (CDA) provocation.&#xD;
Peak nasal inspiratory flow (PNIF) Peak nasal inspiratory flow evaluation is a physiologic measure of air flow through both nasal cavities during forced inspiration. The PNIF can be measured using a portable nasal inspiratory ﬂow meter and is expressed in liters per minute.&#xD;
Cold dry air (CDA) provocation CDA nasal provocation can be performed by delivering compressed dry air through a mask placed over nose and mouth of the patient, while breathing only through the nose. Patients will be exposed during 15 minutes. NHR is defined as a drop in PNIF larger than 20 % from baseline upon CDA challenge.&#xD;
The efficacy of MP29-02 treatment will be evaluated by measuring the change in PNIF values upon CDA exposure in both treatment arms.&#xD;
Unit of measurement of PNIF: L/min</description>
  </other_outcome>
  <other_outcome>
    <measure>change in assessment of visual analogue scale (VAS) for total nasal symptom (TNS) and individual nasal symptoms, rT5SS and Allergic Rhinitis Control Test (ARCT)</measure>
    <time_frame>4 weeks after treatment</time_frame>
    <description>A Visual Analogue Scale (VAS) is a measurement of patient's subjective evaluation of symptom severity. Patients will score the severity of their total nasal symptoms (TNS) on a scale, as well as each individual nasal symptom (rhinorrhea, pruritis, sneezing, nasal obstruction), with 0 meaning no symptoms and 10 meaning the worst symptoms. The cut off value of 5/10 is to distinguish between controlled and uncontrolled AR.&#xD;
Patients will score their reflective nasal and ocular symptoms on a 4-point scale from absent (0), mild (1), moderate (2) to severe (3)). Minimum score: 0/15 as having no trouble with any of the symptoms; and maximum score: 15/15 as having maximum trouble with all the symptoms&#xD;
The Allergic Rhinitis Control Test (ARCT): Patients score the five questions from 1 (always troublesome) to 5 (never troublesome). Minimum score: 5/25 ; maximum score: 25/25. A score from 5/25 to 20/25 is assumed not controlled AR; a score higher then 20/25 is assumed controlled.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Allergic Rhinitis</condition>
  <condition>House Dust Mite Allergy</condition>
  <arm_group>
    <arm_group_label>azelastine + fluticasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>azelastine 137 µg + fluticasone 50 µg combined applied twice daily one puff in each nostril duration: 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>twice daily one puff in each nostril duration: 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>azelastine + fluticasone</intervention_name>
    <arm_group_label>azelastine + fluticasone</arm_group_label>
    <other_name>dymista</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with an ARIA-based diagnosis of persistent moderate/severe AR (≥ 2 nasal&#xD;
             symptoms suggestive of allergic rhinitis and positive skin prick tests to house dust&#xD;
             mite (HDM) (HAL Allergy, Leiden, The Netherlands) at screening. Patients with&#xD;
             additional seasonal pollen allergies may be included providing that they are included&#xD;
             outside their individual pollen season, and with VAS score for total nasal symptoms of&#xD;
             more than 5&#xD;
&#xD;
          2. VAS for TNS of more than 5, and rT5SS of more than 8 at both screening and&#xD;
             randomization&#xD;
&#xD;
          3. Age &gt; 18 and &lt; 60 years&#xD;
&#xD;
          4. Eosinophilia of more than 5% in nasal secretions at screening&#xD;
&#xD;
          5. Nasal hyperreactivity (drop of PNIF &gt;20 %) at randomization&#xD;
&#xD;
          6. Possibility to give reliable information and written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any evidence of clinically relevant acute or chronic cardiovascular, pulmonary,&#xD;
             hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental,&#xD;
             neurological, or other disease at screening&#xD;
&#xD;
          2. History of allergic reaction to fluticasone propionate, azelastine hydrochloride or&#xD;
             one of the excipients (e.g. benzalkonium chloride, phenylethyl alcohol,&#xD;
             microcrystalline cellulose)&#xD;
&#xD;
          3. Patients with a change in vision or with a history of increased ocular pressure,&#xD;
             glaucoma and/or cataracts&#xD;
&#xD;
          4. Patients with tuberculosis, any type of untreated infection, or recent surgical&#xD;
             operation or injury to the nose or mouth&#xD;
&#xD;
          5. Patients on prolonged use of decongestive nose sprays, suffering from so-called&#xD;
             rhinitis medicamentosa&#xD;
&#xD;
          6. Patients using other nasal or oral medication affecting nasal function, like nasal&#xD;
             corticosteroids, anticholinergics, cromoglycates, leukotriene antagonists, ACE&#xD;
             inhibitors during the study or within the last 14 days before randomization; patients&#xD;
             using oral corticosteroids during the last 30 days&#xD;
&#xD;
          7. Patients using cytochrome P450 inhibitors (e.g. ritonavir)&#xD;
&#xD;
          8. Nasal endoscopic evidence of rhinosinusitis with or without nasal polyposis (NP) or&#xD;
             structural abnormalities such as clinically relevant septal deviation (septum reaching&#xD;
             concha inferior or lateral nasal wall) or septal perforation at screening&#xD;
&#xD;
          9. Patients on immunotherapy (IT) for HDM or with history of IT for HDM&#xD;
&#xD;
         10. Patients with a psychiatric, addictive, or any disorder of which the investigators&#xD;
             feel that this may compromise the ability to give truly informed consent for&#xD;
             participation in this study or provide reliable information on the questionnaire&#xD;
&#xD;
         11. Patients being enrolled in other clinical trials within the last 3 months&#xD;
&#xD;
         12. Pregnancy or breastfeeding&#xD;
&#xD;
         13. Malignancies or severe comorbidity&#xD;
&#xD;
         14. Smoking&#xD;
&#xD;
         15. Use of anticoagulation medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>peter hellings, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UZ Leuven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Uz Leuven Dienst Nko</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams Brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>emily dekimpe, Msc</last_name>
      <email>emily.dekimpe@uzleuven.be</email>
    </contact>
    <investigator>
      <last_name>peters hellings, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>August 22, 2013</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>December 2, 2015</last_update_submitted>
  <last_update_submitted_qc>December 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2015</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>Dust Mite Allergy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Azelastine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02238353
org study id: azelastine/fluticasone AZE/FLU
nct id: NCT02238353
lead sponsor: 
has dmc: No
Comparative analysis of the efficacy of intranasal MP29-02 (a novel formulation of azelastine
      and FP) has already been conducted in patients with moderate-to-severe seasonal AR. The
      combination formulation appeared to be superior in these patients with better symptomatic
      relief. However, objective analysis of the effect of this treatment on nasal mediators and/or
      nasal hyperreactivity has not yet been performed and would help in understanding the
      additional benefit of the combination treatment over monotherapy with nasal corticosteroids.
Comparative analysis of the efficacy of intranasal MP29-02 (a novel formulation of azelastine
      and FP) has already been conducted in patients with moderate-to-severe seasonal AR. The
      combination formulation appeared to be superior in these patients with better symptomatic
      relief. However, objective analysis of the effect of this treatment on nasal mediators and/or
      nasal hyperreactivity has not yet been performed and would help in understanding the
      additional benefit of the combination treatment over monotherapy with nasal corticosteroids.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: change in expression of inflammatory mediators (Histamine / Substance P / IL-5 / EPO)
time frame: 4 weeks after treatment
description: Change in expression of inflammatory mediators (Histamine / Substance P / interleukin 5 (IL-5) / EPO) at after 4 weeks of therapy with AZE/FP or placebo nasal spray.
Unit of measurement: µg/ml
measure: change in PNIF values upon CDA exposure
time frame: 4 weeks treatment
description: Nasal hyperreactivity (NHR) can be assessed with peak nasal inspiratory flow (PNIF) measurement before and after cold dry air (CDA) provocation.
Peak nasal inspiratory flow (PNIF) Peak nasal inspiratory flow evaluation is a physiologic measure of air flow through both nasal cavities during forced inspiration. The PNIF can be measured using a portable nasal inspiratory ﬂow meter and is expressed in liters per minute.
Cold dry air (CDA) provocation CDA nasal provocation can be performed by delivering compressed dry air through a mask placed over nose and mouth of the patient, while breathing only through the nose. Patients will be exposed during 15 minutes. NHR is defined as a drop in PNIF larger than 20 % from baseline upon CDA challenge.
The efficacy of MP29-02 treatment will be evaluated by measuring the change in PNIF values upon CDA exposure in both treatment arms.
Unit of measurement of PNIF: L/min
measure: change in assessment of visual analogue scale (VAS) for total nasal symptom (TNS) and individual nasal symptoms, reflective total of 5 symptom scores (rT5SS) and Allergic Rhinitis Control Test (ARCT)
time frame: 1 week after treatment
description: A Visual Analogue Scale (VAS) is a measurement of patient's subjective evaluation of symptom severity. Patients will score the severity of their total nasal symptoms (TNS) on a scale, as well as each individual nasal symptom (rhinorrhea, pruritis, sneezing, nasal obstruction), with 0 meaning no symptoms and 10 meaning the worst symptoms. The cut off value of 5/10 is to distinguish between controlled and uncontrolled AR.
Patients will score their reflective nasal and ocular symptoms on a 4-point scale from absent (0), mild (1), moderate (2) to severe (3)). Minimum score: 0/15 as having no trouble with any of the symptoms; and maximum score: 15/15 as having maximum trouble with all the symptoms
The Allergic Rhinitis Control Test (ARCT): Patients score the five questions from 1 (always troublesome) to 5 (never troublesome). Minimum score: 5/25 ; maximum score: 25/25. A score from 5/25 to 20/25 is assumed not controlled AR; a score higher then 20/25 is assumed controlled.
measure: Effects of therapy with AZE/FP or placebo on nasal inflammatory mediators (Histamine / Substance P (SP) / IL-5 / EPO)
time frame: one week after treatment
description: Change in expression of inflammatory mediators (Histamine / Substance P / IL-5 / EPO) at after 1 week of therapy with AZE/FP or placebo nasal spray.
Unit of measurement: µg/ml
measure: change in PNIF values upon CDA exposure
time frame: 1 week of treatment
description: Nasal hyperreactivity (NHR) can be assessed with peak nasal inspiratory flow (PNIF) measurement before and after cold dry air (CDA) provocation.
Peak nasal inspiratory flow (PNIF) Peak nasal inspiratory flow evaluation is a physiologic measure of air flow through both nasal cavities during forced inspiration. The PNIF can be measured using a portable nasal inspiratory ﬂow meter and is expressed in liters per minute.
Cold dry air (CDA) provocation CDA nasal provocation can be performed by delivering compressed dry air through a mask placed over nose and mouth of the patient, while breathing only through the nose. Patients will be exposed during 15 minutes. NHR is defined as a drop in PNIF larger than 20 % from baseline upon CDA challenge.
The efficacy of MP29-02 treatment will be evaluated by measuring the change in PNIF values upon CDA exposure in both treatment arms.
Unit of measurement of PNIF: L/min
measure: change in assessment of visual analogue scale (VAS) for total nasal symptom (TNS) and individual nasal symptoms, rT5SS and Allergic Rhinitis Control Test (ARCT)
time frame: 4 weeks after treatment
description: A Visual Analogue Scale (VAS) is a measurement of patient's subjective evaluation of symptom severity. Patients will score the severity of their total nasal symptoms (TNS) on a scale, as well as each individual nasal symptom (rhinorrhea, pruritis, sneezing, nasal obstruction), with 0 meaning no symptoms and 10 meaning the worst symptoms. The cut off value of 5/10 is to distinguish between controlled and uncontrolled AR.
Patients will score their reflective nasal and ocular symptoms on a 4-point scale from absent (0), mild (1), moderate (2) to severe (3)). Minimum score: 0/15 as having no trouble with any of the symptoms; and maximum score: 15/15 as having maximum trouble with all the symptoms
The Allergic Rhinitis Control Test (ARCT): Patients score the five questions from 1 (always troublesome) to 5 (never troublesome). Minimum score: 5/25 ; maximum score: 25/25. A score from 5/25 to 20/25 is assumed not controlled AR; a score higher then 20/25 is assumed controlled.
arm group label: azelastine + fluticasone
arm group type: Experimental
description: azelastine 137 µg + fluticasone 50 µg combined applied twice daily one puff in each nostril duration: 4 weeks
arm group label: placebo
arm group type: Placebo Comparator
description: twice daily one puff in each nostril duration: 4 weeks
intervention type: Drug
intervention name: azelastine + fluticasone
arm group label: azelastine + fluticasone
other name: dymista
intervention type: Drug
intervention name: Placebo
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: peter hellings, MD
role: Principal Investigator
affiliation: UZ Leuven
facility: 
status: Recruiting
contact: 
investigator: 
country: Belgium
responsible party type: Sponsor
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
mesh term: Dust Mite Allergy
mesh term: Fluticasone
mesh term: Azelastine