<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/NCT01703052</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-1006-PR-0048</org_study_id>
    <nct_id>NCT01703052</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of Inhaled CHF 6001 in Healthy Volunteers (HV)</brief_title>
  <official_title>A Placebo-controlled Double-blind Single and Repeated Ascending Dose Study to Investigate the Safety and Tolerability of Inhaled CHF 6001 in Healthy Volunteers</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to investigate the safety, tolerability and pharmacokinetics of&#xD;
      inhaled CHF 6001 after single and multiple doses in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted in a single centre and will consist of a single dose part and a&#xD;
      multiple dose part.&#xD;
&#xD;
      Seven single doses of CHF 6001 will be administered according to an escalation, alternate&#xD;
      cross over scheme. Five multiple doses of CHF 6001 will be administered for 7 days according&#xD;
      to a sequential escalation scheme.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2011</start_date>
  <completion_date type="Actual">May 2012</completion_date>
  <primary_completion_date type="Actual">May 2012</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events, adverse drug reactions, serious adverse events.</measure>
    <time_frame>After 7 days of treatment</time_frame>
    <description>The number and percentage of subjects with adverse events, adverse drug reactions, serious adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs</measure>
    <time_frame>After 7 days of treatment</time_frame>
    <description>Blood pressure and Heart rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>12-lead ECG</measure>
    <time_frame>After 7 days of treatment</time_frame>
    <description>Heart rate, RR, PR, QRS, QT, QTcB, QTcF</description>
  </primary_outcome>
  <primary_outcome>
    <measure>24h ECG Holter</measure>
    <time_frame>After 7 days of treatment</time_frame>
    <description>Number and percentages of subjects with arrhythmias ( e.g ventricular tachycardia, supra ventricular tachycardia,..)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FEV1</measure>
    <time_frame>After 7 days of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood and urine Laboratory tests</measure>
    <time_frame>After 7 days of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Body weight</measure>
    <time_frame>After 7 days of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of CHF 6001 and its metabolite</measure>
    <time_frame>After 7 days of treatment</time_frame>
    <description>AUC; Cmax and tmax; t½</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>CHF 6001 SD or placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single administration of CHF 6001 dose levels 1 to 7 or placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF 6001 MD or placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple administration of CHF 6001 dose levels 1 to 5 or placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF 6001 SD or placebo</intervention_name>
    <description>Dry Powder Inhaler</description>
    <arm_group_label>CHF 6001 SD or placebo</arm_group_label>
    <other_name>CHF 6001 DPI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF 6001 MD or placebo</intervention_name>
    <description>Dry Powder Inhaler</description>
    <arm_group_label>CHF 6001 MD or placebo</arm_group_label>
    <other_name>CHF 6001 DPI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject's written informed consent obtained prior to any study-related procedure&#xD;
&#xD;
          -  Male healthy volunteers aged 18-55 years;&#xD;
&#xD;
          -  Able to understand the study procedures, the risks involved and ability to be trained&#xD;
             to use the devices correctly.&#xD;
&#xD;
          -  Body Mass Index (BMI) between 18.0 and 28.0 kg/m2;&#xD;
&#xD;
          -  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; 1 year;&#xD;
&#xD;
          -  Results of laboratory tests within the normal ranges. Minor deviations are acceptable&#xD;
             provided that they are not judged clinically significant by the investigator.&#xD;
&#xD;
          -  A reliable method of contraception for the subjects and their partner.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Blood donation or blood loss less than 8 weeks before inhalation of the study&#xD;
             medication;&#xD;
&#xD;
          -  Positive HIV1 or HIV2 serology;&#xD;
&#xD;
          -  Positive results from the Hepatitis serology which indicates acute or chronic&#xD;
             Hepatitis B or Hepatitis C;&#xD;
&#xD;
          -  History of substance abuse or drug abuse within 12 months prior to screening visit or&#xD;
             with a positive urine drug screen at screening;&#xD;
&#xD;
          -  Clinically relevant abnormal laboratory values suggesting an unknown disease and&#xD;
             requiring further clinical investigation;&#xD;
&#xD;
          -  Clinically significant and uncontrolled cardiac, hepatic, renal, gastrointestinal,&#xD;
             endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with&#xD;
             successful completion of this protocol;&#xD;
&#xD;
          -  Treatment within the previous 3 months with any drug known to have a well defined&#xD;
             potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole).&#xD;
&#xD;
          -  Subjects who refuse to abstain from alcohol or caffeine containing foods or beverages&#xD;
             or grapefruit containing foods or beverages from 48 hour prior to each intake of study&#xD;
             medication until the end of confinement at the clinical centre.&#xD;
&#xD;
          -  Heavy caffeine drinker (&gt; 5 cups or glasses of caffeinated beverages e.g., coffee,&#xD;
             tea, cola per day).&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>Stuart Mair, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quotient Clinical</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quotient Clinical</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Ferrari A, Compagnoni A, Nandeuil A, Maison-Blanche P. Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers. J Cardiovasc Pharmacol. 2016 Jul;68(1):41-8. doi: 10.1097/FJC.0000000000000384.</citation>
    <PMID>26945156</PMID>
  </reference>
  <reference>
    <citation>Jolling K, Abelo A, Luyckx N, Nandeuil MA, Govoni M, Cella M, Lindauer A. Concentration-QT Modeling Following Inhalation of the Novel Inhaled Phosphodiesterase-4 Inhibitor CHF6001 in Healthy Volunteers Shows an Absence of QT Prolongation. CPT Pharmacometrics Syst Pharmacol. 2019 Jul;8(7):460-468. doi: 10.1002/psp4.12405. Epub 2019 May 11.</citation>
    <PMID>31077576</PMID>
  </reference>
  <results_reference>
    <citation>Mariotti F, Govoni M, Lucci G, Santoro D, Nandeuil MA. Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers. Int J Chron Obstruct Pulmon Dis. 2018 Oct 18;13:3399-3410. doi: 10.2147/COPD.S174156. eCollection 2018.</citation>
    <PMID>30425469</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>April 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 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>
  <!-- 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/NCT01703052
org study id: CCD-1006-PR-0048
nct id: NCT01703052
lead sponsor: 
has dmc: Yes
This study is designed to investigate the safety, tolerability and pharmacokinetics of
      inhaled CHF 6001 after single and multiple doses in healthy volunteers.
The study will be conducted in a single centre and will consist of a single dose part and a
      multiple dose part.

      Seven single doses of CHF 6001 will be administered according to an escalation, alternate
      cross over scheme. Five multiple doses of CHF 6001 will be administered for 7 days according
      to a sequential escalation scheme.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Adverse events, adverse drug reactions, serious adverse events.
time frame: After 7 days of treatment
description: The number and percentage of subjects with adverse events, adverse drug reactions, serious adverse events
measure: Vital signs
time frame: After 7 days of treatment
description: Blood pressure and Heart rate
measure: 12-lead ECG
time frame: After 7 days of treatment
description: Heart rate, RR, PR, QRS, QT, QTcB, QTcF
measure: 24h ECG Holter
time frame: After 7 days of treatment
description: Number and percentages of subjects with arrhythmias ( e.g ventricular tachycardia, supra ventricular tachycardia,..)
measure: FEV1
time frame: After 7 days of treatment
measure: Blood and urine Laboratory tests
time frame: After 7 days of treatment
measure: Body weight
time frame: After 7 days of treatment
measure: Pharmacokinetics of CHF 6001 and its metabolite
time frame: After 7 days of treatment
description: AUC; Cmax and tmax; t½
arm group label: CHF 6001 SD or placebo
arm group type: Experimental
description: Single administration of CHF 6001 dose levels 1 to 7 or placebo
arm group label: CHF 6001 MD or placebo
arm group type: Experimental
description: Multiple administration of CHF 6001 dose levels 1 to 5 or placebo
intervention type: Drug
intervention name: CHF 6001 SD or placebo
description: Dry Powder Inhaler
arm group label: CHF 6001 SD or placebo
other name: CHF 6001 DPI
intervention type: Drug
intervention name: CHF 6001 MD or placebo
description: Dry Powder Inhaler
arm group label: CHF 6001 MD or placebo
other name: CHF 6001 DPI
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stuart Mair, MD
role: Principal Investigator
affiliation: Quotient Clinical
facility: 
country: United Kingdom
citation: Ferrari A, Compagnoni A, Nandeuil A, Maison-Blanche P. Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers. J Cardiovasc Pharmacol. 2016 Jul;68(1):41-8. doi: 10.1097/FJC.0000000000000384.
PMID: 26945156
citation: Jolling K, Abelo A, Luyckx N, Nandeuil MA, Govoni M, Cella M, Lindauer A. Concentration-QT Modeling Following Inhalation of the Novel Inhaled Phosphodiesterase-4 Inhibitor CHF6001 in Healthy Volunteers Shows an Absence of QT Prolongation. CPT Pharmacometrics Syst Pharmacol. 2019 Jul;8(7):460-468. doi: 10.1002/psp4.12405. Epub 2019 May 11.
PMID: 31077576
citation: Mariotti F, Govoni M, Lucci G, Santoro D, Nandeuil MA. Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers. Int J Chron Obstruct Pulmon Dis. 2018 Oct 18;13:3399-3410. doi: 10.2147/COPD.S174156. eCollection 2018.
PMID: 30425469
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive