<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/NCT03268226</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-05993AA1-16</org_study_id>
    <secondary_id>2017-000438-79</secondary_id>
    <nct_id>NCT03268226</nct_id>
  </id_info>
  <brief_title>Functional Respiratory Imaging Study (FRI)</brief_title>
  <acronym>FRI</acronym>
  <official_title>Open Label, Prospective, Exploratory Study to Investigate the Effect of Inhaled CHF5993 pMDI on Central and Peripheral Airway Dimensions in COPD Patients by Functional Respiratory Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiesi Farmaceutici S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chiesi Farmaceutici S.p.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of inhaled extrafine CHF5993 pMDI on&#xD;
      airway volumes, and resistance, by Functional Respiratory Imaging (FRI), in COPD patients&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 20, 2017</start_date>
  <completion_date type="Actual">January 30, 2019</completion_date>
  <primary_completion_date type="Actual">January 30, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single Group Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Specific image-based airway volumes (siVaw)</measure>
    <time_frame>Change from baseline at 24 Weeks.</time_frame>
    <description>CT-based airway volumes normalized by the lung volume</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specific image-based airway resistance (siRaw)</measure>
    <time_frame>Change from baseline at 24 Weeks.</time_frame>
    <description>CFD-based airway resistance normalized by the lung volume</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Internal Airflow Distribution</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Air Trapping</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emphysema</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Airway Wall Volume</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood vessel density</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilation/perfusion matching</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aerosol Deposition</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using thorax HRCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Dyspnea</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>mMRC dyspnea scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>Saint George Respiratory Questionnaire (SGRQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CAT score</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>8-items unidimensional questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspnea</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>Borg CR10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dynamic lung volumes</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using spirometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Static lung volumes</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using body plethysmography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>airway resistances</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>calculated using body plethysmography</description>
  </secondary_outcome>
  <other_outcome>
    <measure>exercise tolerance</measure>
    <time_frame>On Week 0, Week 12, and on Week 24</time_frame>
    <description>cycling endurance test (CET)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>CHF5993</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide administered via pMDI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium</intervention_name>
    <description>An inhaled dose of CHF 5993 pMDI 100+6+12.5 μg twice a day (Total daily dose: BDP 400 μg / FF 24 μg / GB 50 μg)</description>
    <arm_group_label>CHF5993</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject's written informed consent obtained prior to any study-related procedure.&#xD;
&#xD;
          2. Male or Female COPD patients aged ≥ 40 years.&#xD;
&#xD;
          3. Smoking history: of at least 10 pack-years (pack-year= number of cigarettes per day x&#xD;
             number of years/20).&#xD;
&#xD;
          4. Smoking status: current or ex-smokers. Previous smokers are defined as those who have&#xD;
             stopped smoking for at least 24 weeks prior to screening visit. (Pipe and/or cigar&#xD;
             and/or e-cigarettes smoking cannot be used to calculate pack-year history). If the&#xD;
             subjects undergo smoking cessation therapy, it must be completed 3 months prior to&#xD;
             study entry.&#xD;
&#xD;
          5. Patients with documented COPD at least 12 months according to GOLD 2017.&#xD;
&#xD;
          6. Post-bronchodilator (BD) decreased Tiffeneau index: FEV1/FVC &lt; 0.70.&#xD;
&#xD;
          7. Patients who present post- BD FEV1 less than 50 % of predicted.&#xD;
&#xD;
          8. Patients who present (Functional residual capacity) FRC ≥120% predicted.&#xD;
&#xD;
          9. Patients who present CAT assessment ≥10.&#xD;
&#xD;
         10. Patients on stable respiratory medications for at least 3 months prior to screening&#xD;
             with non extrafine extemporary triple combination. The possible combination therapies&#xD;
             prior to screening are:&#xD;
&#xD;
               -  fluticasone plus salmeterol plus tiotropium&#xD;
&#xD;
               -  fluticasone plus salmeterol plus glycopyrronium&#xD;
&#xD;
               -  fluticasone plus salmeterol plus umeclidinium&#xD;
&#xD;
               -  fluticasone plus vilanterol plus tiotropium&#xD;
&#xD;
               -  fluticasone plus vilanterol plus glycopyrronium&#xD;
&#xD;
               -  fluticasone plus vilanterol plus umeclidinium;&#xD;
&#xD;
         11. Body Mass Index (BMI) between 18.0 and 32.0 kg/m2 (extremes included) at the screening&#xD;
             visit..&#xD;
&#xD;
         12. Ability to understand the study procedures and the risks involved and ability to be&#xD;
             trained with pMDI training inhalers to use the devices correctly.&#xD;
&#xD;
         13. WOCBP fulfilling one of the following criteria:&#xD;
&#xD;
               1. WOCBP with fertile male partners: they and/or their partner must be willing to&#xD;
                  use a highly effective birth control method from the signature of the informed&#xD;
                  consent and until the follow-up visit or&#xD;
&#xD;
               2. WOCBP with non-fertile male partners (contraception is not required in this&#xD;
                  case).&#xD;
&#xD;
             For the definition of WOCBP and of fertile men and the list of highly effective birth&#xD;
             control methods, refer the CTFG guidance for more detailed information&#xD;
&#xD;
         14. Female patients of non-childbearing potential defined as physiologically incapable of&#xD;
             becoming pregnant (i.e. post-menopausal or permanently sterile; e.g. amenorrehic for&#xD;
             ≥12 consecutive months without alternative medical cause). Permanent sterilisation&#xD;
             methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy (40).&#xD;
             If indicated, as per investigator's request, post-menopausal status may be confirmed&#xD;
             by follicle-stimulating hormone levels (according to local laboratory ranges).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating women.&#xD;
&#xD;
          2. Patients with history or current diagnosis of asthma.&#xD;
&#xD;
          3. Medical history or current diagnosis of allergic rhinitis or atopy (atopy which may&#xD;
             have risen contra-indications or impacted the efficacy of the study treatment&#xD;
             according to Investigator's judgment).&#xD;
&#xD;
          4. Patients requiring use of the following medications:&#xD;
&#xD;
               1. Systemic steroids for COPD exacerbation in the 4 weeks prior to screening;&#xD;
&#xD;
               2. Patients with a moderate or severe COPD exacerbation [i.e. resulting in the use&#xD;
                  of systemic corticosteroids (oral/IV/IM) and/or or antibiotics or need for&#xD;
                  hospitalisation within 6 weeks prior to screening];&#xD;
&#xD;
               3. A course of antibiotics for COPD exacerbation longer than 7 days in the 4 weeks&#xD;
                  prior to screening;&#xD;
&#xD;
               4. c-Phosphodiesterase-4 (PDE-4) inhibitors in the 4 weeks prior to screening;&#xD;
&#xD;
               5. Use of antibiotics for a lower respiratory tract infection (e.g. pneumonia) in&#xD;
                  the 4 weeks prior to screening;&#xD;
&#xD;
          5. Patients treated with non-cardio-selective β-blockers in the week prior to screening.&#xD;
&#xD;
          6. Patients treated with long-acting anti-histamines unless taken at stable regimen at&#xD;
             least 2 months prior to screening and to be maintained constant during the study.&#xD;
&#xD;
          7. Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic&#xD;
             hypoxemia.&#xD;
&#xD;
          8. Known respiratory disorders other than COPD which may impact the efficacy of the study&#xD;
             treatment according the Investigator's judgment. (This could include but is not&#xD;
             limited to α-1 antitrypsin deficiency, active tuberculosis, bronchiectasis,&#xD;
             sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease).&#xD;
&#xD;
          9. Lung cancer or history of lung cancer: patients with a diagnosis of lung cancer or a&#xD;
             history of lung cancer.&#xD;
&#xD;
         10. Lung resection: subjects with a history of lung volume resection.&#xD;
&#xD;
         11. Subjects who have a cardiovascular condition such as, but not limited to unstable&#xD;
             ischemic heart disease, NYHA Class III/IV left ventricular failure, acute ischemic&#xD;
             heart disease in the last year prior to study screening, which may impact the safety&#xD;
             of the subject or the evaluation of the result of the study according to the&#xD;
             Investigator's judgment; history of atrial fibrillation, history of sustained and non&#xD;
             sustained cardiac arrhythmias diagnosed within 24 weeks prior to study entry not&#xD;
             controlled with therapy.&#xD;
&#xD;
         12. ECG criteria: any clinically significant abnormal 12-lead ECG that in the&#xD;
             Investigator's opinion would affect the efficacy or safety evaluation or place the&#xD;
             patients at risk. Male patients with a QTcF &gt;450ms and female patients with a QTcF&#xD;
             &gt;470ms at screening and/or baseline visits are not eligible.&#xD;
&#xD;
         13. Medical history or current diagnosis of narrow-angle glaucoma, clinically relevant&#xD;
             prostatic hypertrophy or bladder neck obstruction that in the opinion of the&#xD;
             Investigator would have prevented use of anticholinergic agents.&#xD;
&#xD;
         14. History of hypersensitivity to M3 antagonists, β2-agonist, corticosteroids or any of&#xD;
             the excipients contained in any of the formulations used in the study which may raise&#xD;
             contra-indications or impacted the efficacy of the study treatment according to the&#xD;
             Investigator's judgment.&#xD;
&#xD;
         15. Clinically significant laboratory abnormalities indicating a significant or unstable&#xD;
             concomitant disease which may have impacted the efficacy or the safety of the study&#xD;
             treatment according to Investigator's judgment.&#xD;
&#xD;
         16. Patients with serum potassium levels &lt; 3.5 mEq/L (or 3.5 mmol/L).&#xD;
&#xD;
         17. Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes&#xD;
             mellitus or other endocrine disease; uncontrolled gastrointestinal disease (e.g.&#xD;
             active peptic ulcer); uncontrolled neurological disease; uncontrolled hematological&#xD;
             disease; uncontrolled autoimmune disorders, or other which may impact the feasibility&#xD;
             of the results of the study according to Investigator's judgment.&#xD;
&#xD;
         18. History of alcohol abuse and/or substance/drug abuse within 12 months prior to&#xD;
             screening.&#xD;
&#xD;
         19. Drugs with hepatoxic potential: Patients receiving treatment with any drug known to&#xD;
             have a well defined potential for hepatotoxicity (e.g. isoniazide, nimesulide,&#xD;
             ketoconazole) within the previous 3 months before the screening visit.&#xD;
&#xD;
         20. Changes in dose, schedule, formulation or product of oral xanthine derivatives (e.g.&#xD;
             Theophylline) in the month prior screening visit.&#xD;
&#xD;
         21. Participation in an investigational trial: patients who have received any&#xD;
             investigational drug within the 30 days (60 days for biologics) before the screening&#xD;
             visit or a more appropriate time as determined by the investigator (e.g. approximately&#xD;
             5 half-lives of the investigational drug whatever is longer).&#xD;
&#xD;
         22. Treatment with strong CYP3A inhibitors (e.g. erythromycin, itraconazole) within 4&#xD;
             weeks prior to study entry.&#xD;
&#xD;
         23. Serology at the screening positive for HIV1 or HIV2 and positive results for Hepatitis&#xD;
             which indicates acute or chronic Hepatitis B (i.e. positive HB surface antigen HBsAg,&#xD;
             positive and/or positive HB core antibody anti-HBc) or Hepatitis C (positive HCV&#xD;
             antibody).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>SGS CPU Antwerpen</name>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Saint-Maarten</name>
      <address>
        <city>Duffel</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre medical Erpent - Residence</name>
      <address>
        <city>Erpent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heilige Familie AZ</name>
      <address>
        <city>Reet</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Koranyi Institute for TB and Pulmonology</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Hungary</country>
  </location_countries>
  <link>
    <url>https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-000438-79/results</url>
    <description>Study Record on EU Clinical Trials Register including results.</description>
  </link>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</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>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Beclomethasone</mesh_term>
    <mesh_term>Glycopyrrolate</mesh_term>
    <mesh_term>Formoterol Fumarate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03268226
org study id: CCD-05993AA1-16
secondary id: 2017-000438-79
nct id: NCT03268226
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the effect of inhaled extrafine CHF5993 pMDI on
      airway volumes, and resistance, by Functional Respiratory Imaging (FRI), in COPD patients
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Specific image-based airway volumes (siVaw)
time frame: Change from baseline at 24 Weeks.
description: CT-based airway volumes normalized by the lung volume
measure: Specific image-based airway resistance (siRaw)
time frame: Change from baseline at 24 Weeks.
description: CFD-based airway resistance normalized by the lung volume
measure: Internal Airflow Distribution
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Air Trapping
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Emphysema
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Airway Wall Volume
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Blood vessel density
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Ventilation/perfusion matching
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Aerosol Deposition
time frame: On Week 0, Week 12, and on Week 24
description: calculated using thorax HRCT
measure: Functional Dyspnea
time frame: On Week 0, Week 12, and on Week 24
description: mMRC dyspnea scale
measure: Quality of life
time frame: On Week 0, Week 12, and on Week 24
description: Saint George Respiratory Questionnaire (SGRQ)
measure: CAT score
time frame: On Week 0, Week 12, and on Week 24
description: 8-items unidimensional questionnaire
measure: Dyspnea
time frame: On Week 0, Week 12, and on Week 24
description: Borg CR10
measure: Dynamic lung volumes
time frame: On Week 0, Week 12, and on Week 24
description: calculated using spirometry
measure: Static lung volumes
time frame: On Week 0, Week 12, and on Week 24
description: calculated using body plethysmography
measure: airway resistances
time frame: On Week 0, Week 12, and on Week 24
description: calculated using body plethysmography
measure: exercise tolerance
time frame: On Week 0, Week 12, and on Week 24
description: cycling endurance test (CET)
arm group label: CHF5993
arm group type: Experimental
description: Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide administered via pMDI
intervention type: Drug
intervention name: Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium
description: An inhaled dose of CHF 5993 pMDI 100+6+12.5 μg twice a day (Total daily dose: BDP 400 μg / FF 24 μg / GB 50 μg)
arm group label: CHF5993
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Hungary
url: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-000438-79/results
description: Study Record on EU Clinical Trials Register including results.
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Beclomethasone
mesh term: Glycopyrrolate
mesh term: Formoterol Fumarate
sharing ipd: No