<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/NCT02986321</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-06001AA1-01</org_study_id>
    <secondary_id>2015-005548-32</secondary_id>
    <nct_id>NCT02986321</nct_id>
  </id_info>
  <brief_title>A 24-wk Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of a New PDE4 Inhibitor in Patients With COPD</brief_title>
  <acronym>PIONEER</acronym>
  <official_title>A 24-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo and Active Controlled, Parallel Group, Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF6001 DPI in Patients With COPD on a Background Therapy</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 dose-response relationship of different doses of&#xD;
      CHF6001 and to identify the optimal dose (s) in terms of benefit/risk ratio for further&#xD;
      development in the target patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II, randomized, double-blind, double-dummy, placebo and active controlled&#xD;
      multinational, multicenter, dose ranging, 6-arm parallel-group study to identify the optimal&#xD;
      dose of CHF6001, PDE4 inhibitor under development, with respect to lung functions and&#xD;
      symptoms.&#xD;
&#xD;
      After a 2-wk run-in period under formoterol (Oxis Turbohaler®) and rescue salbutamol prn,&#xD;
      patients will be randomized to one of the 6 treatment groups. After the randomization,&#xD;
      patients will be assessed after 3, 6, 12, 18 and 24 weeks of treatment at clinic/hospital. A&#xD;
      follow-up visit will be performed 12 days after the last visit.&#xD;
&#xD;
      During the study, patients will report daily symptoms with the EXACT-PRO/E-RS questionnaire,&#xD;
      rescue/background medication use and compliance with the study medications. AEs, SAEs and&#xD;
      COPD exacerbations will be monitored throughout the study. At randomization and subsequent&#xD;
      visits, patients will undergo physical and vital signs examinations, spirometry measurement,&#xD;
      12-lead ECG. Symptoms and Health status will be assessed through validated questionnaires.&#xD;
      Routine lab analysis and blood biomarkers will be done.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 15, 2016</start_date>
  <completion_date type="Actual">January 9, 2018</completion_date>
  <primary_completion_date type="Actual">October 4, 2017</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in predose morning FEV1 at 12 weeks</measure>
    <time_frame>week 12</time_frame>
    <description>overall effect of CHF6001 on change from baseline in predose morning FEV1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in predose morning FEV1 at other timepoints</measure>
    <time_frame>weeks 3, 6, 18, 24</time_frame>
    <description>Change from Baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in pre-dose morning IC</measure>
    <time_frame>weeks 3, 6, 12, 18, 24</time_frame>
    <description>Change from Baseline for other lung function parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in pre-dose morning FVC</measure>
    <time_frame>weeks 3, 6, 12, 18, 24</time_frame>
    <description>Change from Baseline for other lung function parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in TDI focal score</measure>
    <time_frame>weeks 3, 6, 12, 18, 24</time_frame>
    <description>Change of TDI score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in SGRQ score</measure>
    <time_frame>weeks 3, 6, 12, 18, 24</time_frame>
    <description>Change of SGRQ score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in E-RS score</measure>
    <time_frame>weeks 3, 6, 12, 18, 24</time_frame>
    <description>Change of E-RSI score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>COPD exacerbation rate over 24 weeks of treatment</measure>
    <time_frame>24 weeks</time_frame>
    <description>exacerbation rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first COPD exacerbation</measure>
    <time_frame>24 weeks</time_frame>
    <description>Time to first COPD exacerbation</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">1130</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>CHF6001 DOSE1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DOSE1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF6001 DOSE2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DOSE2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF6001 DOSE3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DOSE3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF6001 DOSE4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DOSE4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Matched placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo control</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Budesonide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Budesonide DPI 800µg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF6001</intervention_name>
    <description>Dose response: Test one of 4 different doses of CHF6001</description>
    <arm_group_label>CHF6001 DOSE1</arm_group_label>
    <arm_group_label>CHF6001 DOSE2</arm_group_label>
    <arm_group_label>CHF6001 DOSE3</arm_group_label>
    <arm_group_label>CHF6001 DOSE4</arm_group_label>
    <other_name>Dose range finding</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Budesonide</intervention_name>
    <description>active control</description>
    <arm_group_label>Budesonide</arm_group_label>
    <other_name>Active comparator</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo control</description>
    <arm_group_label>Matched placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD patients&#xD;
&#xD;
          -  Non- childbearing potential or woman permanently sterilized or on one or more highly&#xD;
             effective contraception&#xD;
&#xD;
          -  Current/ex smokers (history &gt; 10 pack years)&#xD;
&#xD;
          -  Post bronchodilatator FEV1 &gt;=30% and &lt;=70% predicted normal value and FEV1/FVC ratio&#xD;
             &lt;0.7&#xD;
&#xD;
          -  Documented history of at least 1 moderate or severe exacerbation in the 12 months&#xD;
             prior to study entry&#xD;
&#xD;
          -  Symptomatic patients (MMRC score ≥2 and a CAT score ≥10)&#xD;
&#xD;
          -  Patients on daily maintenance therapy with an ICS/LABA .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of asthma or other respiratory disorders&#xD;
&#xD;
          -  Maintenance bronchodilators therapy only (eg LABA alone)&#xD;
&#xD;
          -  Maintenance triple therapy.&#xD;
&#xD;
          -  Occurrence of a moderate or severe COPD exacerbation within 6 weeks prior to study&#xD;
             entry or during the run-in period.&#xD;
&#xD;
          -  Patients requiring long term oxygen therapy.&#xD;
&#xD;
          -  Concomitant or recent pulmonary rehabilitation programme&#xD;
&#xD;
          -  Known respiratory disorders other than COPD&#xD;
&#xD;
          -  Lung cancer or a history of lung cancer, active or history of cancer with less than 5&#xD;
             years disease free survival time&#xD;
&#xD;
          -  Hypersensitivity to β2-agonist, corticosteroids, PDE4 inhibitors or any of the&#xD;
             excipients&#xD;
&#xD;
          -  Depression, generalised anxiety disorder, suicidal ideation&#xD;
&#xD;
          -  Any clinically significant cardiovascular disease (IM, CHF III/IV; AF not controlled&#xD;
             by therapy, etc) within 1 year of study entry&#xD;
&#xD;
          -  Any relevant clinically significant cardiovascular condition, clinically abnormal&#xD;
             significant 12-lead ECG (QTcF&gt;450 ms for male and &gt;470 for female) or clinically&#xD;
             significant laboratory abnormalities&#xD;
&#xD;
          -  Serum potassium value ≤3.5 mEq/L or &gt;5.5mEq/L and/or a fasting serum glucose value&#xD;
             ≥140 mg/dL.&#xD;
&#xD;
          -  History or symptoms of significant neurological disease&#xD;
&#xD;
          -  Unstable concurrent disease: eg uncontrolled Thyroid disease or other endocrine&#xD;
             diseases, gastrointestinal uncontrolled disease, uncontrolled immune diseases&#xD;
&#xD;
          -  Renal impairment.&#xD;
&#xD;
          -  Patients with abnormal alanine aminotransferase and/ or aspartate aminotransferase&#xD;
             and/or bilirubin&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             and patients receiving treatment with any drug known to have a well defined potential&#xD;
             for hepatotoxicity before Study entry&#xD;
&#xD;
          -  Severely obese (BMI ≥35 kg/m2) or have experienced excessive weight loss recently&#xD;
&#xD;
          -  History of alcohol abuse and/or substance/drug abuse within 12 months prior to&#xD;
             screening visit.&#xD;
&#xD;
          -  Any recent participation to a clinical Study with other investigational drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dave Singh</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medicines Evaluation Unit, Manchester, UK</affiliation>
  </overall_official>
  <link>
    <url>https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005548-32</url>
    <description>Study Record on EU Clinical Trials Register including results</description>
  </link>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 24, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>January 25, 2019</last_update_submitted>
  <last_update_submitted_qc>January 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anti-inflammatory respiratory drug</keyword>
  <keyword>PDE4 inhibitor</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>Budesonide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02986321
org study id: CCD-06001AA1-01
secondary id: 2015-005548-32
nct id: NCT02986321
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the dose-response relationship of different doses of
      CHF6001 and to identify the optimal dose (s) in terms of benefit/risk ratio for further
      development in the target patient population.
This is a phase II, randomized, double-blind, double-dummy, placebo and active controlled
      multinational, multicenter, dose ranging, 6-arm parallel-group study to identify the optimal
      dose of CHF6001, PDE4 inhibitor under development, with respect to lung functions and
      symptoms.

      After a 2-wk run-in period under formoterol (Oxis Turbohaler®) and rescue salbutamol prn,
      patients will be randomized to one of the 6 treatment groups. After the randomization,
      patients will be assessed after 3, 6, 12, 18 and 24 weeks of treatment at clinic/hospital. A
      follow-up visit will be performed 12 days after the last visit.

      During the study, patients will report daily symptoms with the EXACT-PRO/E-RS questionnaire,
      rescue/background medication use and compliance with the study medications. AEs, SAEs and
      COPD exacerbations will be monitored throughout the study. At randomization and subsequent
      visits, patients will undergo physical and vital signs examinations, spirometry measurement,
      12-lead ECG. Symptoms and Health status will be assessed through validated questionnaires.
      Routine lab analysis and blood biomarkers will be done.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in predose morning FEV1 at 12 weeks
time frame: week 12
description: overall effect of CHF6001 on change from baseline in predose morning FEV1
measure: Change from baseline in predose morning FEV1 at other timepoints
time frame: weeks 3, 6, 18, 24
description: Change from Baseline
measure: Change from baseline in pre-dose morning IC
time frame: weeks 3, 6, 12, 18, 24
description: Change from Baseline for other lung function parameters
measure: Change from baseline in pre-dose morning FVC
time frame: weeks 3, 6, 12, 18, 24
description: Change from Baseline for other lung function parameters
measure: Change from baseline in TDI focal score
time frame: weeks 3, 6, 12, 18, 24
description: Change of TDI score
measure: Change from baseline in SGRQ score
time frame: weeks 3, 6, 12, 18, 24
description: Change of SGRQ score
measure: Change from baseline in E-RS score
time frame: weeks 3, 6, 12, 18, 24
description: Change of E-RSI score
measure: COPD exacerbation rate over 24 weeks of treatment
time frame: 24 weeks
description: exacerbation rate
measure: Time to first COPD exacerbation
time frame: 24 weeks
description: Time to first COPD exacerbation
arm group label: CHF6001 DOSE1
arm group type: Experimental
description: DOSE1
arm group label: CHF6001 DOSE2
arm group type: Experimental
description: DOSE2
arm group label: CHF6001 DOSE3
arm group type: Experimental
description: DOSE3
arm group label: CHF6001 DOSE4
arm group type: Experimental
description: DOSE4
arm group label: Matched placebo
arm group type: Placebo Comparator
description: placebo control
arm group label: Budesonide
arm group type: Active Comparator
description: Budesonide DPI 800µg
intervention type: Drug
intervention name: CHF6001
description: Dose response: Test one of 4 different doses of CHF6001
arm group label: CHF6001 DOSE1
arm group label: CHF6001 DOSE2
arm group label: CHF6001 DOSE3
arm group label: CHF6001 DOSE4
other name: Dose range finding
intervention type: Drug
intervention name: Budesonide
description: active control
arm group label: Budesonide
other name: Active comparator
intervention type: Drug
intervention name: Placebo
description: placebo control
arm group label: Matched placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Dave Singh
role: Principal Investigator
affiliation: Medicines Evaluation Unit, Manchester, UK
url: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005548-32
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: Budesonide
sharing ipd: Undecided