<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/NCT02975843</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-05993AA1-15</org_study_id>
    <secondary_id>2016-001088-35</secondary_id>
    <nct_id>NCT02975843</nct_id>
  </id_info>
  <brief_title>Lung Deposition of Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide Administered Via pMDI in Healthy, Asthmatic and COPD Patients</brief_title>
  <official_title>Open Label, Uncontrolled, Non-randomized, Single Dose, Scintigraphic Study to Investigate Lung Deposition of Inhaled 99mTc Radiolabelled CHF5993 pMDI in Healthy Volunteers, Asthmatic and COPD Patients</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the lung deposition and distribution pattern of&#xD;
      Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide using a&#xD;
      Gamma-scintigraphic technique after inhalation of a single dose of 99mTc radiolabelled CHF&#xD;
      5993 Administered via pMDI in healthy volunteers, asthmatic and COPD patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2016</start_date>
  <completion_date type="Actual">April 11, 2017</completion_date>
  <primary_completion_date type="Actual">March 21, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intrapulmonary Lung deposition expressed as % of nominal dose</measure>
    <time_frame>Immediately after dosing</time_frame>
    <description>Calculated using the individual Gamma camera images</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Distribution of lung deposition</measure>
    <time_frame>Immediately after dosing</time_frame>
    <description>Calculated using the individual Gamma camera images</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extrathoracic deposition</measure>
    <time_frame>Immediately after dosing</time_frame>
    <description>Calculated using the individual Gamma camera images</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exhaled activity</measure>
    <time_frame>Immediately after dosing</time_frame>
    <description>Calculated using the individual Gamma camera images</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDP/B17MP, Formoterol, and GB Area under curve (AUC) 0-t</measure>
    <time_frame>the area under the plasma concentration-time curve from 0 to the last quantifiable concentration. Over 24h</time_frame>
    <description>Calculated through plasma samples for PK evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDP/B17MP, Formoterol, and GB Area under curve (AUC) 0-30min</measure>
    <time_frame>area under the plasma concentration-time curve from 0 to 30 min post-dose</time_frame>
    <description>Calculated through plasma samples for PK evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDP/B17MP, Formoterol, and GB area under the curve (AUC) 0-∞</measure>
    <time_frame>area under the curve extrapolated to infinity over 24h</time_frame>
    <description>Calculated through plasma samples for PK evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDP/B17MP, Formoterol, and GB Peak Plasma Concentration (Cmax)</measure>
    <time_frame>the value of the maximum plasma concentration will be obtained directly from the experimental data without interpolation. Over 24h</time_frame>
    <description>Calculated through plasma samples for PK evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDP/B17MP, Formoterol, and GB tmax</measure>
    <time_frame>time of the maximum plasma concentration will be obtained directly from the experimental data without interpolation. Over 24h</time_frame>
    <description>Calculated through plasma samples for PK evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDP/B17MP, Formoterol, and GB t½</measure>
    <time_frame>the terminal (apparent elimination) half-life over 24h</time_frame>
    <description>Calculated through plasma samples for PK evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lung function assessment</measure>
    <time_frame>Over 24 h post dose</time_frame>
    <description>Calculated using spirometry</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>CHF5993</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99mTc Radiolabelled 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>single inhalation of 99mTc radiolabelled CHF 5993 pMDI (4 puffs for a total dose of: Beclometasone diproprionate (BDP) 400 μg, Formoterol fumarate (FF) 24 μg, Glycopirronium bromide (GB) 50 μg)</description>
    <arm_group_label>CHF5993</arm_group_label>
    <other_name>CHF5993 pMDI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for all subjects:&#xD;
&#xD;
          1. Subject's written informed consent obtained prior to any study-related procedure&#xD;
&#xD;
          2. Body mass index (BMI) between 18 and 32 kg/m2&#xD;
&#xD;
          3. Ability to understand the study procedures and the risks involved and ability to be&#xD;
             trained to use the devices correctly at screening and pre-dose.&#xD;
&#xD;
          4. Normal vital signs (Diastolic BP 60-90 mmHg, Systolic BP 90-140 mmHg or 90-150 if &gt;45&#xD;
             yrs) at screening and pre-dose.&#xD;
&#xD;
          5. 12-lead digitalised ECG considered as normal: 60 ≤ heart rate ≤ 100 bpm, 120 ms ≤ PR&#xD;
             ≤210 ms, QRS ≤ 120 ms, QTcF ≤ 450 ms (male) and ≤ 470 ms (female) at screening and&#xD;
             pre-dose&#xD;
&#xD;
          6. Males fulfilling one of the following criteria:&#xD;
&#xD;
               1. Males with non-pregnant Women of childbearing potential (WOCBP) partners: they&#xD;
                  and/or their partner of childbearing potential must be willing to use a highly&#xD;
                  effective birth control method in addition to the male condom from the signature&#xD;
                  of the informed consent and until 90 days after the follow-up visit. Subjects&#xD;
                  must not donate sperm during the study and for 90 days after the follow-up visit&#xD;
                  or&#xD;
&#xD;
               2. Males with pregnant WOCBP partner: they must be willing to use male contraception&#xD;
                  (condom) from the signature of the informed consent and until 90 days after the&#xD;
                  follow-up visit. Subjects must not donate sperm during the study and for 90 days&#xD;
                  after the follow-up visit or&#xD;
&#xD;
               3. Non-fertile male subjects (contraception is not required in this case) or&#xD;
&#xD;
               4. Males with partner not of childbearing potential (contraception is not required&#xD;
                  in this case).&#xD;
&#xD;
          7. 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 with low user dependency from the&#xD;
                  signature of the informed consent and until 30 days after the follow-up visit or&#xD;
&#xD;
               2. WOCBP with non-fertile male partners (contraception is not required in this&#xD;
                  case).&#xD;
&#xD;
          8. Female patients of non-childbearing potential defined as physiologically incapable of&#xD;
             becoming pregnant (i.e. post-menopausal or permanently sterile). Tubal ligation or&#xD;
             partial surgical interventions are not acceptable. If indicated, as per investigator's&#xD;
             request, post-menopausal status may be confirmed by follicle-stimulating hormone&#xD;
             levels (according to local laboratory ranges)&#xD;
&#xD;
             Additional Inclusion criteria for Healthy /volunteers and Asthmatic patients:&#xD;
&#xD;
          9. Males and females aged 18-55&#xD;
&#xD;
         10. Non- or Ex-smokers who smoked &lt; 5 pack years (pack-years = number of cigarette packs&#xD;
             per day times the number of years) and stopped smoking &gt; 1 year&#xD;
&#xD;
             Additional Inclusion Criteria only for Healthy volunteers:&#xD;
&#xD;
         11. Lung function within normal limits: FEV1 ≥ 80% of predicted (according to the Global&#xD;
             Lung Function Initiative, ERS Task Force Lung Function Reference Vales) and FEV1/FVC&#xD;
             ratio &gt; 0.70 at screening&#xD;
&#xD;
             Additional Inclusion Criteria only for Asthmatic patients:&#xD;
&#xD;
         12. Pre-bronchodilator 60% ≤ FEV1 ≤ 80% of predicted (according to the Global Lung&#xD;
             Function Initiative, ERS Task Force Lung Function Reference Vales) and FEV1/FVC ratio&#xD;
             &gt; 0.70 at screening. If this criterion is not met at Screening, the test can be&#xD;
             repeated once before Day -1.&#xD;
&#xD;
         13. Positive reversibility test as defined by an increase in FEV1 ≥ 12% and at least 200&#xD;
             ml compared to the initial value 20-30 minutes after inhalation of 400 μg Salbutamol&#xD;
             at screening. If this criterion is not met at Screening, the test can be repeated once&#xD;
             before Day -1.&#xD;
&#xD;
             Additional Inclusion Criteria only for COPD patients:&#xD;
&#xD;
         14. Males and females aged 40-75&#xD;
&#xD;
         15. Current or ex- smokers (stopped smoking &gt; 1 year ) minimum smoking history of 10&#xD;
             pack-years (packyears = number of cigarette packs per day times the number of years)&#xD;
&#xD;
         16. 30% ≤ FEV1 &lt; 50% of predicted and FEV1/FVC &lt; 0.70 after inhalation of 400 μg&#xD;
             Salbutamol. If this criterion is not met at Screening, the test can be repeated once&#xD;
             before Day -1.&#xD;
&#xD;
        Exclusion Criteria for all subjects:&#xD;
&#xD;
          1. Pregnant or lactating women&#xD;
&#xD;
          2. Documented history of drug abuse (within 12 months before screening) and/or positive&#xD;
             urine drug test at screening and/or at treatment period&#xD;
&#xD;
          3. History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of&#xD;
             the excipients contained in any of the formulations used in the trial;&#xD;
&#xD;
          4. Any clinically relevant abnormal laboratory value at screening suggesting an unknown&#xD;
             disease and requiring further clinical investigation or which may impact the safety of&#xD;
             the subject or the evaluation of the result of the study according to the&#xD;
             investigator's judgment&#xD;
&#xD;
          5. Clinically relevant and uncontrolled hepatic, gastrointestinal, renal, genitourinary,&#xD;
             endocrine, metabolic neurologic, or psychiatric disorder that may interfere with&#xD;
             successful completion of this protocol&#xD;
&#xD;
          6. Serology at the screening positive to 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 (HCV antibody);&#xD;
&#xD;
          7. Subjects with history of sustained and non-sustained cardiac arrhythmias (ECG&#xD;
             demonstrated) and subjects with a family history of sudden cardiac death&#xD;
&#xD;
          8. Subjects who have 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&#xD;
&#xD;
          9. Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck&#xD;
             obstruction that in the opinion of the investigator would prevent use of&#xD;
             anticholinergic agents&quot;&#xD;
&#xD;
         10. Significant blood loss ≥ 400 ml within 3 months prior screening and between screening&#xD;
             and Day 1;&#xD;
&#xD;
         11. Participation in another clinical trial with an investigational drug in the previous 3&#xD;
             months before the administration of the study drug; a longer and more appropriate time&#xD;
             could be considered by the principal investigator based on the elimination of the&#xD;
             half-life and/or long term toxicity of the previous investigational drug;&#xD;
&#xD;
         12. Radiation exposure, including that from the present study, excluding background&#xD;
             radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv&#xD;
             in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker,&#xD;
             as defined in the Ionising Radiation Regulations 1999, shall participate in the study.&#xD;
&#xD;
         13. Unsuitable veins for repeated venipuncture&#xD;
&#xD;
         14. Any not allowed concomitant medication&#xD;
&#xD;
             Additional Exclusion criteria for Healthy volunteers and Asthmatic patients:&#xD;
&#xD;
         15. Current use of any nicotine or nicotine replacement product&#xD;
&#xD;
             Additional Exclusion criteria for Asthmatic and COPD patients:&#xD;
&#xD;
         16. Use of systemic steroids in the 4 weeks prior to screening and between screening and&#xD;
             Day 1 (injectable depot steroids 6 weeks)&#xD;
&#xD;
         17. Life-threatening/unstable respiratory status including upper or lower respiratory&#xD;
             tract infection, within the previous 30 days before screening and between screening&#xD;
             and Day 1&#xD;
&#xD;
         18. Requirement for continuous oxygen therapy (supplemental oxygen not exceeding 2 l/min,&#xD;
             at night only and/or during exercise is allowed)&#xD;
&#xD;
             Additional Exclusion criteria only for asthmatic patients:&#xD;
&#xD;
         19. Change in dose or type of any medications for asthma within 4 weeks prior to the&#xD;
             screening visit&#xD;
&#xD;
         20. Asthma exacerbation within the 4 weeks prior screening and between screening and Day 1&#xD;
&#xD;
         21. History of COPD or any chronic respiratory disease other than Asthma&#xD;
&#xD;
             Additional Exclusion criteria only for COPD patients:&#xD;
&#xD;
         22. Change in dose or type of any medications for COPD within 4 weeks prior to the&#xD;
             screening visit&#xD;
&#xD;
         23. COPD exacerbation within the 4 weeks prior screening and between screening and Day 1&#xD;
&#xD;
         24. History of asthma or any chronic respiratory disease other than COPD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>June 22, 2017</last_update_submitted>
  <last_update_submitted_qc>June 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>
  <!-- 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/NCT02975843
org study id: CCD-05993AA1-15
secondary id: 2016-001088-35
nct id: NCT02975843
lead sponsor: 
has dmc: No
The purpose of this study is to investigate the lung deposition and distribution pattern of
      Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide using a
      Gamma-scintigraphic technique after inhalation of a single dose of 99mTc radiolabelled CHF
      5993 Administered via pMDI in healthy volunteers, asthmatic and COPD patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intrapulmonary Lung deposition expressed as % of nominal dose
time frame: Immediately after dosing
description: Calculated using the individual Gamma camera images
measure: Distribution of lung deposition
time frame: Immediately after dosing
description: Calculated using the individual Gamma camera images
measure: Extrathoracic deposition
time frame: Immediately after dosing
description: Calculated using the individual Gamma camera images
measure: Exhaled activity
time frame: Immediately after dosing
description: Calculated using the individual Gamma camera images
measure: BDP/B17MP, Formoterol, and GB Area under curve (AUC) 0-t
time frame: the area under the plasma concentration-time curve from 0 to the last quantifiable concentration. Over 24h
description: Calculated through plasma samples for PK evaluation
measure: BDP/B17MP, Formoterol, and GB Area under curve (AUC) 0-30min
time frame: area under the plasma concentration-time curve from 0 to 30 min post-dose
description: Calculated through plasma samples for PK evaluation
measure: BDP/B17MP, Formoterol, and GB area under the curve (AUC) 0-∞
time frame: area under the curve extrapolated to infinity over 24h
description: Calculated through plasma samples for PK evaluation
measure: BDP/B17MP, Formoterol, and GB Peak Plasma Concentration (Cmax)
time frame: the value of the maximum plasma concentration will be obtained directly from the experimental data without interpolation. Over 24h
description: Calculated through plasma samples for PK evaluation
measure: BDP/B17MP, Formoterol, and GB tmax
time frame: time of the maximum plasma concentration will be obtained directly from the experimental data without interpolation. Over 24h
description: Calculated through plasma samples for PK evaluation
measure: BDP/B17MP, Formoterol, and GB t½
time frame: the terminal (apparent elimination) half-life over 24h
description: Calculated through plasma samples for PK evaluation
measure: lung function assessment
time frame: Over 24 h post dose
description: Calculated using spirometry
arm group label: CHF5993
arm group type: Experimental
description: 99mTc Radiolabelled Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide administered via pMDI
intervention type: Drug
intervention name: Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium
description: single inhalation of 99mTc radiolabelled CHF 5993 pMDI (4 puffs for a total dose of: Beclometasone diproprionate (BDP) 400 μg, Formoterol fumarate (FF) 24 μg, Glycopirronium bromide (GB) 50 μg)
arm group label: CHF5993
other name: CHF5993 pMDI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
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