<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/NCT03795350</url>
  </required_header>
  <id_info>
    <org_study_id>CLI-05993AA1-20</org_study_id>
    <secondary_id>2017-005030-29</secondary_id>
    <nct_id>NCT03795350</nct_id>
  </id_info>
  <brief_title>Lung Deposition of TRIMBOW® pMDI in Healthy Volunteers, Asthmatic and COPD Patients</brief_title>
  <acronym>STORM</acronym>
  <official_title>Open Label, Uncontrolled, Non-randomized, Single Dose, Scintigraphic Study to Investigate Lung Deposition of Inhaled 99mTc Radiolabelled TRIMBOW® 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>
    <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 investigate the lung deposition and distribution pattern of&#xD;
      TRIMBOW using a Gamma-scintigraphic technique after inhalation of a single dose of 99mTc&#xD;
      radiolabelled TRIMBOW administered via pMDI in healthy volunteers, asthmatic and COPD&#xD;
      patients&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    In light of the cessation of non-essential clinical activities at CPU due to the COVID-19&#xD;
    pandemic, the sponsor has determined to terminate the study early.&#xD;
  </why_stopped>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Actual">April 3, 2020</completion_date>
  <primary_completion_date type="Actual">April 3, 2020</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</measure>
    <time_frame>immediately after dosing</time_frame>
    <description>calculated using individual Gamma camera images</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intrapulmonary lung distribution of deposition: C/P ratio</measure>
    <time_frame>immediately after dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>extrathoracic deposition</measure>
    <time_frame>immediately after dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>amount of exhaled drug</measure>
    <time_frame>immediately after dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIMBOW pharmacokinetics - (AUC0-t)</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>Area Under plasma Concentration from 0 to last quantifiable concentration (AUC0-t) for BDP, B17MP, FF and GB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lung function assessment - FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75%</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIMBOW pharmacokinetics - (AUC0-30)</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>area under plasma concentration from 0 to 30 min (AUC0-30) for B17MP, FF and GB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIMBOW pharmacokinetics - (Cmax)</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>Maximum plasma concentration (Cmax) for BDP, B17MP, FF and GB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIMBOW - (tmax)</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>time of the maximum plasma concentration (tmax) for BDP, B17MP, FF and GB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIMBOW pharmacokinetics - (AUC0-∞)</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>area under curve extrapolated to infinity (AUC0-∞) for B17MP, FF and GB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TRIMBOW pharmacokinetics - (t1/2)</measure>
    <time_frame>up to 24 hours post dose</time_frame>
    <description>terminal half-life (t1/2) for B17MP, FF and GB</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>TRIMBOW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: BDP/FF/GB&#xD;
4 puffs of 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 Bromide</intervention_name>
    <description>single inhalation of 99mTc radiolabelled TRIMBOW pMDI (4 puffs for a total dose of 400mcg BDP, 24mcg FF, 50 mcg GB)</description>
    <arm_group_label>TRIMBOW</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria for all subjects:&#xD;
&#xD;
          1. Subject's written informed consent obtained prior to any study-related procedure;&#xD;
&#xD;
          2. Ability to understand the study procedures, the risks involved and ability to&#xD;
             demonstrate correct use of the inhaler using the AIM™ (Aerosol Inhalation Monitor)&#xD;
             Vitalograph®&#xD;
&#xD;
          3. Body Mass Index (BMI) between 18 and 32 kg/m2 extremes inclusive;&#xD;
&#xD;
          4. Good physical status, determined on the basis of the medical history and a general&#xD;
             clinical examination, at screening;&#xD;
&#xD;
          5. Vital signs within normal limits: Diastolic BP 40-90 mmHg, Systolic BP 90-140 mmHg or&#xD;
             90-160 mmHg if &gt;45 yrs&#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. Females of non-childbearing potential defined as physiologically incapable of becoming&#xD;
             pregnant (i.e. post-menopausal or permanently sterile). Tubal ligation or partial&#xD;
             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;
          9. 12 -lead digitised Electrocardiogram (12-lead ECG) considered as normal at screening&#xD;
             and at Day -1&#xD;
&#xD;
        Additional Criteria only for Healthy Volunteers and Asthmatic patients:&#xD;
&#xD;
          1. Male and female subjects aged 28-55 years inclusive;&#xD;
&#xD;
          2. Non- or ex-smokers who smoked &lt; 5 pack years (pack-years = the number of cigarette&#xD;
             packs per day times the number of years) and stopped smoking &gt; 6 months prior to&#xD;
             screening;&#xD;
&#xD;
        Additional Inclusion Criteria only for Healthy Volunteers:&#xD;
&#xD;
        1. Lung function measurements within normal limits at screening: FEV1 equal to or more than&#xD;
        80% of predicted&#xD;
&#xD;
        Additional Inclusion Criteria only for Asthmatic patients:&#xD;
&#xD;
          1. Diagnosis of asthma: Established diagnosis of permanent asthma for at least 12 months&#xD;
             according to GINA guidelines&#xD;
&#xD;
          2. Patients with a pre-bronchodilator 60%≤ FEV1 &lt; 80% of the predicted normal value&#xD;
&#xD;
          3. Patients with a documented reversibility defined as an increase ≥ 12% and 200mL over&#xD;
             baseline within 30 min after inhalation of 400µg salbutamol pMDI&#xD;
&#xD;
        Additional Inclusion Criteria only for COPD patients:&#xD;
&#xD;
          1. Male and female patients aged 40-80 years inclusive&#xD;
&#xD;
          2. A smoking history of at least 10 pack-years&#xD;
&#xD;
          3. Current or ex-smokers are eligible.&#xD;
&#xD;
          4. Established diagnosis of COPD&#xD;
&#xD;
          5. A post-bronchodilator FEV1 ≤ 50% of the predicted normal value and a&#xD;
             post-bronchodilator FEV1/FVC &lt; 0.7 10-15 minutes after 4 puffs (4x100 µg) of&#xD;
             Salbutamol pMDI.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Inclusion criteria for all subjects:&#xD;
&#xD;
          1. Pregnant or lactating women;&#xD;
&#xD;
          2. Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal,&#xD;
             renal, endocrine, metabolic, neurologic, or psychiatric disorders&#xD;
&#xD;
          3. Clinically relevant abnormal laboratory values at screening suggesting an unknown&#xD;
             disease and requiring further clinical investigation&#xD;
&#xD;
          4. Subjects with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or&#xD;
             bladder neck obstruction&#xD;
&#xD;
          5. Positive HIV1 or HIV2 serology at screening&#xD;
&#xD;
          6. Blood donation or blood loss less than 2 months prior screening&#xD;
&#xD;
          7. Participation to another clinical trial where investigational drug was received and&#xD;
             last investigations were performed less than 90 days prior to screening;&#xD;
&#xD;
          8. Documented history of alcohol abuse within 12 months prior to screening or a positive&#xD;
             alcohol breath test&#xD;
&#xD;
          9. Documented history of drug abuse within 12 months prior to screening&#xD;
&#xD;
         10. Positive results from the Hepatitis serology which indicates acute or chronic&#xD;
             Hepatitis B or Hepatitis C at screening&#xD;
&#xD;
         11. 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;
         12. Unsuitable veins for repeated venepuncture/cannulation&#xD;
&#xD;
         13. Intake of non-permitted concomitant medications in the predefined period prior to&#xD;
             screening&#xD;
&#xD;
         14. Radiation exposure, including that from the present study, in the last 12 months&#xD;
&#xD;
         15. Known intolerance/hypersensitivity or contra-indication to treatment&#xD;
&#xD;
        Additional exclusion Criteria only for Healthy volunteers and Asthmatic patients:&#xD;
&#xD;
          1. Positive urine test for cotinine at screening or prior Day 1&#xD;
&#xD;
          2. Current use of any nicotine or nicotine replacement product&#xD;
&#xD;
        Additional exclusion criteria only for Asthmatic and COPD patients:&#xD;
&#xD;
          1. Use of systemic corticosteroids medication within 4 weeks prior to the screening or&#xD;
             slow release corticosteroids within 12 weeks before the screening or prior Day 1&#xD;
&#xD;
          2. A diagnosis of lung cancer or a history of lung cancer&#xD;
&#xD;
          3. A history of lung volume reduction surgery&#xD;
&#xD;
          4. Lower respiratory tract infection that requires use of antibiotics&#xD;
&#xD;
        Additional exclusion Criteria only for Healthy volunteers:&#xD;
&#xD;
        1. Subjects with history of breathing problems&#xD;
&#xD;
        Additional exclusion Criteria only for Asthmatic patients:&#xD;
&#xD;
          1. History of near fatal asthma, hospitalization for asthma in intensive care unit&#xD;
&#xD;
          2. Any change in dose, schedule or formulation in the treatment of asthma in the 4 weeks&#xD;
             prior to the screening visit or prior Day 1&#xD;
&#xD;
          3. Non-persistent asthma:&#xD;
&#xD;
          4. Treatment with chronic systemic corticosteroids or anti IgE or other monoclonal&#xD;
             antibodies&#xD;
&#xD;
          5. Known respiratory disorders other than asthma&#xD;
&#xD;
        Additional exclusion Criteria only for COPD patients:&#xD;
&#xD;
          1. Any change in dose, schedule or formulation in the treatment for COPD in the 4 weeks&#xD;
             prior to the screening&#xD;
&#xD;
          2. A concurrent diagnosis of asthma, in the opinion of the investigator&#xD;
&#xD;
          3. Known respiratory disorder other than COPD that in the Investigator's opinion would&#xD;
             affect efficacy and safety evaluation or place the patient at risk.&#xD;
&#xD;
          4. Oxygen therapy: patients requiring long term (at least 12 hours daily) oxygen therapy&#xD;
             for chronic hypoxemia.&#xD;
&#xD;
          5. Change in dose or type of any medications for COPD within 4 weeks prior to the&#xD;
             screening visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Simbec Research Ltd</name>
      <address>
        <city>Merthyr Tydfil</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Usmani OS, Baldi S, Warren S, Panni I, Girardello L, Rony F, Taylor G, DeBacker W, Georges G. Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study. J Aerosol Med Pulm Drug Deliv. 2022 Aug;35(4):179-185. doi: 10.1089/jamp.2021.0046. Epub 2022 Feb 4.</citation>
    <PMID>35128939</PMID>
  </results_reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>May 2, 2022</last_update_submitted>
  <last_update_submitted_qc>May 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung deposition</keyword>
  <keyword>Gamma scintigraphy</keyword>
  <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>Bromides</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/NCT03795350
org study id: CLI-05993AA1-20
secondary id: 2017-005030-29
nct id: NCT03795350
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the lung deposition and distribution pattern of
      TRIMBOW using a Gamma-scintigraphic technique after inhalation of a single dose of 99mTc
      radiolabelled TRIMBOW 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
time frame: immediately after dosing
description: calculated using individual Gamma camera images
measure: Intrapulmonary lung distribution of deposition: C/P ratio
time frame: immediately after dosing
measure: extrathoracic deposition
time frame: immediately after dosing
measure: amount of exhaled drug
time frame: immediately after dosing
measure: TRIMBOW pharmacokinetics - (AUC0-t)
time frame: up to 24 hours post dose
description: Area Under plasma Concentration from 0 to last quantifiable concentration (AUC0-t) for BDP, B17MP, FF and GB
measure: lung function assessment - FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75%
time frame: up to 24 hours post dose
description: FEV1, FVC, FEV1/FVC, FEF25%, FEF50%, FEF75%
measure: TRIMBOW pharmacokinetics - (AUC0-30)
time frame: up to 24 hours post dose
description: area under plasma concentration from 0 to 30 min (AUC0-30) for B17MP, FF and GB
measure: TRIMBOW pharmacokinetics - (Cmax)
time frame: up to 24 hours post dose
description: Maximum plasma concentration (Cmax) for BDP, B17MP, FF and GB
measure: TRIMBOW - (tmax)
time frame: up to 24 hours post dose
description: time of the maximum plasma concentration (tmax) for BDP, B17MP, FF and GB
measure: TRIMBOW pharmacokinetics - (AUC0-∞)
time frame: up to 24 hours post dose
description: area under curve extrapolated to infinity (AUC0-∞) for B17MP, FF and GB
measure: TRIMBOW pharmacokinetics - (t1/2)
time frame: up to 24 hours post dose
description: terminal half-life (t1/2) for B17MP, FF and GB
arm group label: TRIMBOW
arm group type: Experimental
description: Experimental: BDP/FF/GB
4 puffs of 99mTc Radiolabelled Beclometasone dipropionate/Formoterol Fumarate/Glycopyrronium Bromide administered via pMDI
intervention type: Drug
intervention name: Beclometasone dipropionate Formoterol Fumarate Glycopyrronium Bromide
description: single inhalation of 99mTc radiolabelled TRIMBOW pMDI (4 puffs for a total dose of 400mcg BDP, 24mcg FF, 50 mcg GB)
arm group label: TRIMBOW
criteria: 
gender: All
minimum age: 28 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
citation: Usmani OS, Baldi S, Warren S, Panni I, Girardello L, Rony F, Taylor G, DeBacker W, Georges G. Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study. J Aerosol Med Pulm Drug Deliv. 2022 Aug;35(4):179-185. doi: 10.1089/jamp.2021.0046. Epub 2022 Feb 4.
PMID: 35128939
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Beclomethasone
mesh term: Glycopyrrolate
mesh term: Bromides
mesh term: Formoterol Fumarate
sharing ipd: No