<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/NCT03004495</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-06302AA1-02</org_study_id>
    <nct_id>NCT03004495</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Interaction and the Safety of Inhaled CHF5259 and CHF6001</brief_title>
  <official_title>Open Label, Randomized, Repeated-dose, 3-way Crossover Study to Investigate Pharmacokinetic Interaction and the Safety of Inhaled CHF5259 and CHF6001 Administered in Healthy Subjects Via NEXThaler® Dry Powder Inhaler</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiesi Farmaceutici S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quintiles, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Chiesi Farmaceutici S.p.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate systemic pharmacokinetics of CHF6001 following concomitant administration of&#xD;
      CHF6001 and CHF5259, in comparison with the single components, administered in healthy&#xD;
      subjects via a multi-dose reservoir NEXThaler® DPI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is randomised open label, 3-way cross-over study. Each 14-day treatment period is&#xD;
      separated from the following one by a 21-day wash-out period. Subjects will reside at the&#xD;
      clinic facilities during the 14 days treatment period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">August 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma CHF 5259 and CHF 6001 AUC 0-12,ss (area under the plasma concentration-time curve from time 0 to 12h post dose at steady on Day 14)</measure>
    <time_frame>On Day 1 and Day 14 at pre-dose, within 15 minutes from dosing and at the following time points, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post morning dose. At Day 8, Day 12 and Day 13 at pre-dose</time_frame>
    <description>To evaluate the pharmacokinetic interaction between CHF 5259 and CHF 6001</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma CHF 5259 and CHF 6001 Cmax,ss (maximum plasma concentration at steady state on Day 14)</measure>
    <time_frame>On Day 1 and Day 14 at pre-dose, within 15 minutes from dosing and at the following time points, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post morning dose. At Day 8, Day 12 and Day 13 at pre-dose</time_frame>
    <description>To evaluate the pharmacokinetic interaction between CHF 5259 and CHF 6001</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma CHF 5259 and CHF 6001 and its metabolites (CHF 5956, CHF 6095) AUC0-12h, Cmax, tmax</measure>
    <time_frame>On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Holter extracted ECG parameters</measure>
    <time_frame>On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function</measure>
    <time_frame>On Day 1, Day 14: at pre-dose, 5, 15, 30, 45 min and 1, 2 hours post-morning dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital signs</measure>
    <time_frame>On Day 1, Day 8 and on Day 14 at the following time points: pre-dose, 15 min, 30 min, 1, 2, 4, 8, 12 h post morning dose. From Day 2 to Day 13 at pre-morning dose only, On Day 15 (24 h after last dose), Day 16 (48 h after last dose) and at follow-up. (BP</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma CHF 5259 and CHF 6001 and its metabolites (CHF 5956, CHF 6095) Cmax</measure>
    <time_frame>On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma CHF 5259 and CHF 6001 and its metabolites (CHF 5956, CHF 6095) tmax</measure>
    <time_frame>On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Copd</condition>
  <arm_group>
    <arm_group_label>CHF5259 and CHF6001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>(T): CHF6001 + CHF5259 b.i.d. for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF5259 + placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(R1): CHF5259 25µg b.i.d. for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF6001 + placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(R2): CHF6001 b.i.d. for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF5259 and CHF6001</intervention_name>
    <description>b.i.d. for 14 days</description>
    <arm_group_label>CHF5259 and CHF6001</arm_group_label>
    <other_name>Test Treatment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF5259 + placebo</intervention_name>
    <description>b.i.d. for 14 days</description>
    <arm_group_label>CHF5259 + placebo</arm_group_label>
    <other_name>Reference Treatment 1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF6001 + placebo</intervention_name>
    <description>b.i.d. for 14 days</description>
    <arm_group_label>CHF6001 + placebo</arm_group_label>
    <other_name>Reference Treatment 2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>b.i.d. for 14 days</description>
    <arm_group_label>CHF5259 + placebo</arm_group_label>
    <arm_group_label>CHF6001 + placebo</arm_group_label>
    <other_name>Matching number of inhalations</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject's written informed consent obtained prior to any study-related procedure;&#xD;
             Healthy males and females volunteers aged 18-55 years inclusive;&#xD;
&#xD;
          -  Ability to understand the study procedures and the involved risks, ability to be&#xD;
             trained to use the device correctly&#xD;
&#xD;
          -  Non smokers or ex-smokers are eligible.&#xD;
&#xD;
          -  Good physical and mental status, determined on the basis of the medical history and a&#xD;
             general clinical examination;&#xD;
&#xD;
          -  Vital signs checked at screening visit and Day -1: Subjects aged 18-45years: Diastolic&#xD;
             BP 40-90, Systolic BP 90-140; Subjects aged 46-55 years: Diastolic BP 40-90, Systolic&#xD;
             BP 90-150&#xD;
&#xD;
          -  12-lead digitised Electrocardiogram (12-lead ECG) considered as normal (40≤Heart&#xD;
             rate≤110bpm,120 ms ≤ PR ≤ 210 ms, QRS ≤ 120 ms, QTcF ≤ 450 ms for males and ≤ 470ms&#xD;
             for females) checked at screening;&#xD;
&#xD;
          -  Lung function measurements within normal limits: FEV1 &gt; 80% of predicted normal value&#xD;
             (according to the Global Lung Function Initiative, ERS Task Force Lung Function&#xD;
             Reference Values (1,2) ) and FEV1/FVC ratio &gt; 0.70;&#xD;
&#xD;
          -  Male subjects: they and/or their partner of childbearing potential must be willing to&#xD;
             use a double contraceptive methods;&#xD;
&#xD;
          -  Female subject of non-childbearing potential (WONCBP) Female subjects of childbearing&#xD;
             potential (WOCBP) fulfilling one of the following criteria: WOCBP with fertile male&#xD;
             partners: they and/or their partner of childbearing potential must be willing to use a&#xD;
             double contraceptive methods including one highly effective birth control method and&#xD;
             one acceptable birth control method, from the signature of the informed consent and&#xD;
             until three months following the last study drug intake; WOCBP with non-fertile male&#xD;
             partners: contraception is not required in this case.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women:&#xD;
&#xD;
          -  Blood donation (equal or more than 450 ml) or blood loss less than 12 weeks before&#xD;
             inhalation of the study medication;&#xD;
&#xD;
          -  Positive HIV1 or HIV2 serology; Positive results from the Hepatitis serology which&#xD;
             indicates acute or chronic Hepatitis B or Hepatitis C (positive HB surface antigen&#xD;
             (HBsAg),HB core antibody ( anti HBc), HC antibody);&#xD;
&#xD;
          -  History of substance abuse or drug abuse within 12 months prior to screening visit;&#xD;
&#xD;
          -  Clinically significant abnormal 24-h Holter ECG at screening as defined in the Holter&#xD;
             interpretative guidelines (Appendix V);&#xD;
&#xD;
          -  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;
          -  Clinically significant and uncontrolled respiratory, cardiac, hepatic, renal,&#xD;
             gastrointestinal, endocrine, metabolic, neurologic, respiratory or psychiatric&#xD;
             disorder that may interfere with successful completion of this protocol;&#xD;
&#xD;
          -  Subjects with medical diagnosis asthma including childhood asthma;&#xD;
&#xD;
          -  Subjects known to have intolerance/ hypersensitivity to M3 Antagonists, or any of the&#xD;
             excipients contained in any of the formulations used in the trial;&#xD;
&#xD;
          -  Any drug treatment, including prescribed or OTC medicines as well as vitamins,&#xD;
             homeopathic remedies etc, taken in the 14 days (3 months for any biologic drugs,&#xD;
             enzyme-inducing or enzyme-inhibiting drugs e.g., glucocorticoids, phenobarbital,&#xD;
             isoniazid) before the screening visit, with the exception of occasional paracetamol&#xD;
             (maximum 2 g per day with a maximum of 10 g per 14 days for mild non-excluding&#xD;
             conditions), hormonal contraceptives and hormonal replacement treatment for&#xD;
             post-menopausal women;&#xD;
&#xD;
          -  Treatment within the previous 3 months before the screening visit with any drug known&#xD;
             to have a well defined potential for hepatotoxicity (e.g. isoniazide, nimesulide,&#xD;
             ketoconazole);&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronnie Beboso, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quintiles, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quintiles CPU</name>
      <address>
        <city>London</city>
        <state>UK</state>
        <zip>SE1 1 YR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>October 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>December 22, 2016</last_update_submitted>
  <last_update_submitted_qc>December 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT03004495
org study id: CCD-06302AA1-02
nct id: NCT03004495
lead sponsor: 
collaborator: 
has dmc: No
To evaluate systemic pharmacokinetics of CHF6001 following concomitant administration of
      CHF6001 and CHF5259, in comparison with the single components, administered in healthy
      subjects via a multi-dose reservoir NEXThaler® DPI.
This is randomised open label, 3-way cross-over study. Each 14-day treatment period is
      separated from the following one by a 21-day wash-out period. Subjects will reside at the
      clinic facilities during the 14 days treatment period.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Plasma CHF 5259 and CHF 6001 AUC 0-12,ss (area under the plasma concentration-time curve from time 0 to 12h post dose at steady on Day 14)
time frame: On Day 1 and Day 14 at pre-dose, within 15 minutes from dosing and at the following time points, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post morning dose. At Day 8, Day 12 and Day 13 at pre-dose
description: To evaluate the pharmacokinetic interaction between CHF 5259 and CHF 6001
measure: Plasma CHF 5259 and CHF 6001 Cmax,ss (maximum plasma concentration at steady state on Day 14)
time frame: On Day 1 and Day 14 at pre-dose, within 15 minutes from dosing and at the following time points, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post morning dose. At Day 8, Day 12 and Day 13 at pre-dose
description: To evaluate the pharmacokinetic interaction between CHF 5259 and CHF 6001
measure: Plasma CHF 5259 and CHF 6001 and its metabolites (CHF 5956, CHF 6095) AUC0-12h, Cmax, tmax
time frame: On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.
measure: Holter extracted ECG parameters
time frame: On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.
measure: Lung function
time frame: On Day 1, Day 14: at pre-dose, 5, 15, 30, 45 min and 1, 2 hours post-morning dose
measure: Vital signs
time frame: On Day 1, Day 8 and on Day 14 at the following time points: pre-dose, 15 min, 30 min, 1, 2, 4, 8, 12 h post morning dose. From Day 2 to Day 13 at pre-morning dose only, On Day 15 (24 h after last dose), Day 16 (48 h after last dose) and at follow-up. (BP
measure: Plasma CHF 5259 and CHF 6001 and its metabolites (CHF 5956, CHF 6095) Cmax
time frame: On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.
measure: Plasma CHF 5259 and CHF 6001 and its metabolites (CHF 5956, CHF 6095) tmax
time frame: On Day 1, Day 14 at the following time points: pre-dose, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12 h post-morning dose.
arm group label: CHF5259 and CHF6001
arm group type: Experimental
description: (T): CHF6001 + CHF5259 b.i.d. for 14 days
arm group label: CHF5259 + placebo
arm group type: Active Comparator
description: (R1): CHF5259 25µg b.i.d. for 14 days
arm group label: CHF6001 + placebo
arm group type: Active Comparator
description: (R2): CHF6001 b.i.d. for 14 days
intervention type: Drug
intervention name: CHF5259 and CHF6001
description: b.i.d. for 14 days
arm group label: CHF5259 and CHF6001
other name: Test Treatment
intervention type: Drug
intervention name: CHF5259 + placebo
description: b.i.d. for 14 days
arm group label: CHF5259 + placebo
other name: Reference Treatment 1
intervention type: Drug
intervention name: CHF6001 + placebo
description: b.i.d. for 14 days
arm group label: CHF6001 + placebo
other name: Reference Treatment 2
intervention type: Other
intervention name: Placebo
description: b.i.d. for 14 days
arm group label: CHF5259 + placebo
arm group label: CHF6001 + placebo
other name: Matching number of inhalations
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ronnie Beboso, MD
role: Principal Investigator
affiliation: Quintiles, Inc.
facility: 
country: United Kingdom
responsible party type: Sponsor
sharing ipd: No