<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/NCT01706484</url>
  </required_header>
  <id_info>
    <org_study_id>CRS-02</org_study_id>
    <secondary_id>2011-003623-35</secondary_id>
    <nct_id>NCT01706484</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Two Dosages of a Herbal Medicinal Product (Dry Extract BNO 1016) in Chronic Rhinosinusitis</brief_title>
  <official_title>A Multicentre, Randomised, Double-blind, Placebo-controlled, Parallel Group Trial to Assess Efficacy and Safety of Two Dosages of a Herbal Medicinal Product (Dry Extract BNO 1016) in Patients With Chronic Rhinosinusitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bionorica SE</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bionorica SE</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to determine whether 2 different dosages of a herbal extract&#xD;
      (240 and 480 mg/day) are more effective than placebo in the treatment of patients with&#xD;
      chronic rhinosinusitis (average reduction of investigator's Major Symptom Score over Visit 5&#xD;
      and Visit 6.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The clinical trial population consists of patients presenting with two or more typical&#xD;
      symptoms of CRS and duration of symptoms of at least ≥12 weeks. The diagnosis should have&#xD;
      been confirmed with the initial diagnosis of CRS by nasal endoscopy and/or computer&#xD;
      tomography (CT) and by obligatory nasal endoscopy including exclusion of nasal polyps during&#xD;
      screening phase.&#xD;
&#xD;
      A total of 885 patients will be included in this clinical trial, which will last for&#xD;
      approximately 12 months, including screening, treatment and medication-free follow-up period&#xD;
      as well as final reporting. The duration for the individual patient is approximately 22 weeks&#xD;
      (Visit 1 - Visit 7). After a 2-week screening phase, treatment will be started by application&#xD;
      of either 240 mg or 480 mg daily dose (t.i.d.) or placebo for 12 weeks followed by a&#xD;
      medication-free follow-up period.&#xD;
&#xD;
      Symptoms often do not correlate to the findings in nasal endoscopy or CT. Therefore, efficacy&#xD;
      in this clinical trial is defined as per clinical definition using five individual&#xD;
      rhinosinusitis symptoms (MSS)graded by the investigator using increasing severity grading(0 =&#xD;
      absent [none / not present], 1 = mild, 2 = moderate, 3 = severe).&#xD;
&#xD;
      Secondary outcome measures include&#xD;
&#xD;
        -  single rhinosinusitis symptoms of CRS (MSSINV and MSSPAT),&#xD;
&#xD;
        -  Work Productivity and Activity Impairment patient questionnaire related to General&#xD;
           Health [WPAI:GH],&#xD;
&#xD;
        -  total symptom severity by Visual Analogue Scale&#xD;
&#xD;
        -  response to treatment rated by investigator and patient&#xD;
&#xD;
        -  20-Question Sino-Nasal Outcome Test [SNOT-20, only Germany]&#xD;
&#xD;
        -  percentage of patients with permitted concomitant medication for the treatment of CRS&#xD;
&#xD;
        -  premature termination due to exacerbations of symptoms&#xD;
&#xD;
        -  post treatment course of CRS will&#xD;
&#xD;
        -  pharmacoeconomic assessments&#xD;
&#xD;
        -  safety and tolerability of trial treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">April 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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Average of investigator's Major Symptom Score ratings [score points] at V5 and V6</measure>
    <time_frame>4 weeks</time_frame>
    <description>The primary efficacy endpoint is defined as the average of investigator's Major Symptom Score ratings [score points] at V5 and V6 (arithmetic mean of 2 ratings).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient´s MSS ratings [score points] from V5 to V6</measure>
    <time_frame>4 weeks</time_frame>
    <description>Arithmetic mean of approximately 28 ratings, Diary data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigtor´s MSS ratings [score points] at V3</measure>
    <time_frame>Day 8</time_frame>
    <description>CRF data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator´s MSS ratings [score points] at V4</measure>
    <time_frame>Day 29</time_frame>
    <description>CRF data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigtor´s MSS ratings [score points] at V5</measure>
    <time_frame>Day 57</time_frame>
    <description>CRF data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigtor´s MSS ratings [score points] at V6</measure>
    <time_frame>Day 85</time_frame>
    <description>CRF data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigtor´s MSS ratings [score points] at V7</measure>
    <time_frame>Day 141</time_frame>
    <description>CRF data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responders based on investigators´ ratings at V2, V3, V4, V5, V6 and V7</measure>
    <time_frame>20 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responders based on patients´ ratings at V2, V3, V4, V5, V6 and V7</measure>
    <time_frame>20 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>CRS-related absenteeism from work</measure>
    <time_frame>20 weeks</time_frame>
    <description>CRF data</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">927</enrollment>
  <condition>Chronic Sinusitis</condition>
  <arm_group>
    <arm_group_label>80 mg BNO 1016 und placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 tablets (one containing 80 mg BNO 1016 and one placebo) by mouth 3 times daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>160 mg BNO 1016</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 tablets (each containing 80 mg BNO 1016) by mouth 3 times daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>2 tablets (each without BNO 1016) by mouth 3 times daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BNO 1016</intervention_name>
    <description>comparison of different dosages of drug and placebo</description>
    <arm_group_label>160 mg BNO 1016</arm_group_label>
    <arm_group_label>80 mg BNO 1016 und placebo</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
    <other_name>herbal plant extract,</other_name>
    <other_name>sinupret extract mite</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent including data protection declaration&#xD;
&#xD;
          -  Male and female outpatients aged ≥18 and ≤75 years&#xD;
&#xD;
          -  Diagnosis of bilateral chronic rhinosinusitis without nasal polyps confirmed by:&#xD;
&#xD;
               -  nasal endoscopy during the screening period (nasal endoscopy results not older&#xD;
                  than 2 month will be accepted) to confirm inflammation, mucopurulent discharge&#xD;
                  and/or oedema/mucosal obstruction primarily in middle meatus without nasal polyps&#xD;
                  being present&#xD;
&#xD;
               -  at the discretion of the investigator a historic CT (before screening and not&#xD;
                  older than 24 months) will be considered additionally for confirmation of&#xD;
                  bilateral involvement of middle meatus and paranasal sinuses without resolution&#xD;
                  of symptoms (mucosal changes within the ostiomeatal complex and/or sinuses)&#xD;
&#xD;
          -  Bilateral chronic rhinosinusitis characterized by (V1 and V2):&#xD;
&#xD;
               -  presence of chronic rhinosinusitis symptoms for at least 12 weeks without&#xD;
                  complete resolution of symptoms prior to enrolment (V1)&#xD;
&#xD;
               -  a MSS ≥6 points and ≤12 points for each of the screening days observed by diary&#xD;
                  entries (MSSPAT)and on the days of Visit 1 and 2 (MSSINV)&#xD;
&#xD;
               -  on 5 random days of the screening period (or at least at days -5 to -1) assessed&#xD;
                  by MSSPAT and on the day of Visit 1 and 2 assessed by MSSINV: rhinorrhoea&#xD;
                  (anterior or posterior) and pain (facial pain or headache) of at least moderate&#xD;
                  intensity (score ≥2).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Sinus surgery within the last 2 years (solitary sinus puncture is allowed)&#xD;
&#xD;
          -  Nasal concha surgery within the last 3 months&#xD;
&#xD;
          -  Presence or history of uni- or bilateral nasal polyps&#xD;
&#xD;
          -  Presence of moderate to severe co-morbid asthma, including allergic asthma&#xD;
&#xD;
          -  Patients with mild asthma having exacerbations within 30 days prior to trial inclusion&#xD;
&#xD;
          -  Patients with cystic fibrosis&#xD;
&#xD;
          -  Patients with a positive skin prick test at V1 against allergens to which the patient&#xD;
             might be exposed to during the expected individual trial duration, if clinically&#xD;
             relevant (results not older than 12 months will be accepted)&#xD;
&#xD;
          -  Clinically relevant perennial (e.g. patients with actual clinical symptoms of allergic&#xD;
             rhinitis against house dust/-mite antigen) or actual seasonal allergic rhinitis&#xD;
&#xD;
          -  Rhinitis medicamentosa (drug induced rhinitis)&#xD;
&#xD;
          -  Aspirin-Exacerbated Respiratory Disease [AERD] (Aspirin sensitivity)&#xD;
&#xD;
          -  Dentogenic sinusitis or otherwise unilateral sinusitis&#xD;
&#xD;
          -  Presence of anatomical deviations of the nasal septum that significantly impair nasal&#xD;
             and paranasal ventilation / airflow&#xD;
&#xD;
          -  Known hypersensitivity to trial medication or excipients&#xD;
&#xD;
          -  Patients with rare hereditary problems of fructose intolerance, galactose intolerance,&#xD;
             lactase deficiency or glucose-galactose malabsorption or sucrase-isomaltase&#xD;
             insufficiency&#xD;
&#xD;
          -  Signs or symptoms of acute bacterial sinusitis (e.g. fever &gt; 38.5°C, orbital&#xD;
             complications,severe unilateral frontal headache or toothache)&#xD;
&#xD;
          -  Treatment with systemic or nasal antibiotics or corticosteroids within the last 4&#xD;
             weeks prior to V1&#xD;
&#xD;
          -  Treatment with decongestant preparations (α-sympathomimetics), analgesics (including&#xD;
             systemic Non-Steroidal Inflammatory Drugs [NSAIDs], except paracetamol), mucolytics /&#xD;
             secretolytics, antihistamines, or alternative medicine preparations for treatment of&#xD;
             common cold like symptoms or with immunomodulating properties within the last 7 days&#xD;
             prior to V1&#xD;
&#xD;
          -  Patients with gastric or duodenal ulcer&#xD;
&#xD;
          -  Other diseases within 5 years prior to V1, which in the opinion of the investigator&#xD;
             disqualifies the patient for trial enrolment (e.g. liver or kidney disease, severe&#xD;
             somatopathic, neurological and /or psychiatric diseases, history of malignancy or&#xD;
             alcohol or drug abuse or immunodeficiency).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claus Bachert, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ghent University Hospital; Ear, Nose, Throat Medicine, Head &amp; Neck Surgery; Upper Airway Research Laboratory - UZ Gent; De Pintelaan 185 / 1P1; 9000 Gent; Belgium.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Claus Bachert, Prof. Dr.</name>
      <address>
        <city>Ghent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <last_update_submitted>July 7, 2014</last_update_submitted>
  <last_update_submitted_qc>July 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>randomized clinical trial</keyword>
  <keyword>chronic rhinosinusitis</keyword>
  <keyword>herbal extract BNO 1016</keyword>
  <keyword>exacerbation</keyword>
  <keyword>pharmacoeconomic</keyword>
  <keyword>quality of life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sinusitis</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>August 21, 2023</submitted>
  </pending_results>
  <!-- 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/NCT01706484
org study id: CRS-02
secondary id: 2011-003623-35
nct id: NCT01706484
lead sponsor: 
has dmc: No
The purpose of this trial is to determine whether 2 different dosages of a herbal extract
      (240 and 480 mg/day) are more effective than placebo in the treatment of patients with
      chronic rhinosinusitis (average reduction of investigator's Major Symptom Score over Visit 5
      and Visit 6.
The clinical trial population consists of patients presenting with two or more typical
      symptoms of CRS and duration of symptoms of at least ≥12 weeks. The diagnosis should have
      been confirmed with the initial diagnosis of CRS by nasal endoscopy and/or computer
      tomography (CT) and by obligatory nasal endoscopy including exclusion of nasal polyps during
      screening phase.

      A total of 885 patients will be included in this clinical trial, which will last for
      approximately 12 months, including screening, treatment and medication-free follow-up period
      as well as final reporting. The duration for the individual patient is approximately 22 weeks
      (Visit 1 - Visit 7). After a 2-week screening phase, treatment will be started by application
      of either 240 mg or 480 mg daily dose (t.i.d.) or placebo for 12 weeks followed by a
      medication-free follow-up period.

      Symptoms often do not correlate to the findings in nasal endoscopy or CT. Therefore, efficacy
      in this clinical trial is defined as per clinical definition using five individual
      rhinosinusitis symptoms (MSS)graded by the investigator using increasing severity grading(0 =
      absent [none / not present], 1 = mild, 2 = moderate, 3 = severe).

      Secondary outcome measures include

        -  single rhinosinusitis symptoms of CRS (MSSINV and MSSPAT),

        -  Work Productivity and Activity Impairment patient questionnaire related to General
           Health [WPAI:GH],

        -  total symptom severity by Visual Analogue Scale

        -  response to treatment rated by investigator and patient

        -  20-Question Sino-Nasal Outcome Test [SNOT-20, only Germany]

        -  percentage of patients with permitted concomitant medication for the treatment of CRS

        -  premature termination due to exacerbations of symptoms

        -  post treatment course of CRS will

        -  pharmacoeconomic assessments

        -  safety and tolerability of trial treatment
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Average of investigator's Major Symptom Score ratings [score points] at V5 and V6
time frame: 4 weeks
description: The primary efficacy endpoint is defined as the average of investigator's Major Symptom Score ratings [score points] at V5 and V6 (arithmetic mean of 2 ratings).
measure: Patient´s MSS ratings [score points] from V5 to V6
time frame: 4 weeks
description: Arithmetic mean of approximately 28 ratings, Diary data
measure: Investigtor´s MSS ratings [score points] at V3
time frame: Day 8
description: CRF data
measure: Investigator´s MSS ratings [score points] at V4
time frame: Day 29
description: CRF data
measure: Investigtor´s MSS ratings [score points] at V5
time frame: Day 57
description: CRF data
measure: Investigtor´s MSS ratings [score points] at V6
time frame: Day 85
description: CRF data
measure: Investigtor´s MSS ratings [score points] at V7
time frame: Day 141
description: CRF data
measure: Responders based on investigators´ ratings at V2, V3, V4, V5, V6 and V7
time frame: 20 weeks
measure: Responders based on patients´ ratings at V2, V3, V4, V5, V6 and V7
time frame: 20 weeks
measure: CRS-related absenteeism from work
time frame: 20 weeks
description: CRF data
arm group label: 80 mg BNO 1016 und placebo
arm group type: Experimental
description: 2 tablets (one containing 80 mg BNO 1016 and one placebo) by mouth 3 times daily
arm group label: 160 mg BNO 1016
arm group type: Experimental
description: 2 tablets (each containing 80 mg BNO 1016) by mouth 3 times daily
arm group label: placebo
arm group type: Placebo Comparator
description: 2 tablets (each without BNO 1016) by mouth 3 times daily
intervention type: Drug
intervention name: BNO 1016
description: comparison of different dosages of drug and placebo
arm group label: 160 mg BNO 1016
arm group label: 80 mg BNO 1016 und placebo
arm group label: placebo
other name: herbal plant extract,
other name: sinupret extract mite
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Claus Bachert, Prof. Dr.
role: Principal Investigator
affiliation: Ghent University Hospital; Ear, Nose, Throat Medicine, Head & Neck Surgery; Upper Airway Research Laboratory - UZ Gent; De Pintelaan 185 / 1P1; 9000 Gent; Belgium.
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Sinusitis
submitted: August 21, 2023