<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/NCT03236233</url>
  </required_header>
  <id_info>
    <org_study_id>PC_RSV_001</org_study_id>
    <secondary_id>2016-000934-22</secondary_id>
    <nct_id>NCT03236233</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Safety and Tolerability of Single and Repeat Doses of PC786</brief_title>
  <official_title>A Randomised, Single-blind, Placebo-controlled, Dose-escalation Study to Assess the Safety and Tolerability of Single and Repeat, Inhaled Doses of PC786 in Healthy Subjects Combined With a Randomised, Single-blind, Placebo-controlled, Parallel Group to Assess the Safety and Tolerability of a Single Dose of Inhaled PC786 in Subjects With Mild Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pulmocide Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pulmocide Ltd</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>
      This study investigates the safety, tolerability and pharmacokinetics of single and repeat&#xD;
      doses of PC786.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 21, 2017</start_date>
  <completion_date type="Actual">December 15, 2017</completion_date>
  <primary_completion_date type="Actual">December 15, 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants reporting one or more treatment-emergent adverse events (TEAE)</measure>
    <time_frame>Baseline up to Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who discontinue due to an adverse event (AE)</measure>
    <time_frame>Baseline up to Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who meet the markedly abnormal criteria for safety 12-lead ECG assessment at least once post dose</measure>
    <time_frame>Baseline up to Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who meet the markedly abnormal criteria for vital signs assessment at least once post dose</measure>
    <time_frame>Baseline up to Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who meet the markedly abnormal criteria for safety laboratory assessments at least once once post dose</measure>
    <time_frame>Baseline up to Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who meet the markedly abnormal criteria for safety spirometry assessment (FEV1 &amp; FVC - measured together) at least once once post dose</measure>
    <time_frame>Baseline up to Week 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of PC786</measure>
    <time_frame>Day 1: Pre-dose and at multiple time points (up to 10 days) post final dose</time_frame>
    <description>Blood levels of PC786 measured after dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucosal lining fluid concentration of PC786</measure>
    <time_frame>Cohort 1 - Day 1 = 3 samples; Day 2 = 2 samples; Day 3 = 1 sample. Cohorts 2 &amp; 3 - Day 1 = 2 samples; Day 6 = 1 sample; Day 7 = 3 samples; Day 8 = 2 samples; Days 9 &amp; 10 - 1 sample</time_frame>
    <description>PC786 concentration data in mucosal lining fluid measured after dosing</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Respiratory Syncytial Virus (RSV)</condition>
  <arm_group>
    <arm_group_label>Single dose - healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Repeat dose - healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Single dose - subjects with asthma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PC786 - Single doses</intervention_name>
    <description>Safety and tolerability of single doses</description>
    <arm_group_label>Single dose - healthy subjects</arm_group_label>
    <arm_group_label>Single dose - subjects with asthma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Single doses</intervention_name>
    <description>Safety and tolerability of single doses</description>
    <arm_group_label>Single dose - healthy subjects</arm_group_label>
    <arm_group_label>Single dose - subjects with asthma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PC786 - Repeat doses</intervention_name>
    <description>Safety and tolerability of repeat doses</description>
    <arm_group_label>Repeat dose - healthy subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Repeat doses</intervention_name>
    <description>Safety and tolerability of repeat doses</description>
    <arm_group_label>Repeat dose - healthy subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All subjects (Cohorts 1, 2, 3 &amp; 4)&#xD;
&#xD;
          -  Must be male or female, aged between 18 and 65 years inclusive (at the time of&#xD;
             consent) who fit one of the following criteria: women of childbearing potential who&#xD;
             are willing and able to use contraception from screening until 30 days after receipt&#xD;
             of the final dose; Women of non-childbearing potential defined as being amenorrhoeic&#xD;
             or have been permanently sterilised; Men who are willing and able to use contraception&#xD;
             from the time of the first dose, until 90 days after receipt of the final dose of&#xD;
             study medication.&#xD;
&#xD;
          -  Females must have a negative serum β human chorionic gonadotropin (β-hCG) test at&#xD;
             screening and a negative urinary pregnancy test at Day -1.&#xD;
&#xD;
          -  Subject must be willing and able to adhere to the restrictions and prohibitions&#xD;
             required by this protocol.&#xD;
&#xD;
          -  Each subject must sign an informed consent form (ICF) indicating that he or she&#xD;
             understands the purpose and requirements of the study and that they are willing to&#xD;
             participate.&#xD;
&#xD;
          -  Body weight ≥ 50 kg and body mass index (BMI) within the range 18 - 30 kg/m2&#xD;
             (inclusive).&#xD;
&#xD;
          -  Average QTcF &lt;450 msec at screening and pre-dose.&#xD;
&#xD;
          -  Vital signs assessments within normal ranges at screening and pre-dose.&#xD;
&#xD;
        Healthy Subjects (Cohorts 1, 2 &amp; 3)&#xD;
&#xD;
          -  Healthy as determined by a physician based on a full medical examination including&#xD;
             medical history, physical examination and laboratory tests performed at screening and&#xD;
             pre-dose.&#xD;
&#xD;
          -  Spirometry readings (FEV1 and FVC) to be ≥ 80% of predicted value and FEV1/FVC ratio &gt;&#xD;
             0.7 at screening&#xD;
&#xD;
        Subjects with Asthma (Cohort 4)&#xD;
&#xD;
          -  Documented diagnosis of asthma, first diagnosed at least 12 months prior to the&#xD;
             screening visit.&#xD;
&#xD;
          -  Subject must demonstrate a PC20 methacholine ≤ 8 mg/mL at the screening visit.&#xD;
&#xD;
          -  Have an FEV1 &gt;60% of predicted normal value at least 6 h after the last use of a short&#xD;
             acting β-agonist (SABA).&#xD;
&#xD;
          -  Have stable asthma based on physician assessment at screening and prior to&#xD;
             randomisation&#xD;
&#xD;
          -  Subject must be otherwise healthy on the basis of a full medical examination including&#xD;
             medical history, physical examination and laboratory tests performed at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All subjects (Cohorts 1, 2, 3 &amp; 4)&#xD;
&#xD;
          -  Any acute illness.&#xD;
&#xD;
          -  Upper or lower respiratory tract infection within 4 weeks of the screening visit or&#xD;
             randomisation.&#xD;
&#xD;
          -  Use of prescription medications within 14 days of the Screening visit&#xD;
&#xD;
          -  Are taking over the counter medications other than vitamins or multivitamins and&#xD;
             herbal medication, within 14 days prior to Screening&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study of an average&#xD;
             weekly intake of &gt;21 units for males, or &gt;14 units for females&#xD;
&#xD;
          -  Definite or suspected history of drug or alcohol abuse within the previous 5 years.&#xD;
&#xD;
          -  A smoker (regular or irregular), or has smoked or used nicotine-containing products&#xD;
             (including e-cigarettes) within the 6 months prior to screening&#xD;
&#xD;
          -  A positive test for HIV-1 &amp; -2 antibodies at screening.&#xD;
&#xD;
          -  A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody&#xD;
             result at screening.&#xD;
&#xD;
          -  Positive test for alcohol, smoking or drugs of abuse, at screening or pre-dose&#xD;
&#xD;
          -  Received an experimental drug or used an experimental medical device within 3 months&#xD;
             before the first dose of the study drug is scheduled.&#xD;
&#xD;
          -  Allergy to any of the active or inactive ingredients in the study medication.&#xD;
&#xD;
          -  History of drug, or other allergy that would contraindicate participation.&#xD;
&#xD;
          -  Donation of blood in excess of 500 mL within a 3 month period prior to dosing&#xD;
&#xD;
          -  Mentally or legally incapacitated.&#xD;
&#xD;
          -  An employee of the Sponsor or contract research organisation (CRO), or a relative of&#xD;
             an employee of the Sponsor or CRO.&#xD;
&#xD;
          -  Unable or unwilling to undergo multiple venepuncture procedures&#xD;
&#xD;
          -  Pregnant or lactating female&#xD;
&#xD;
          -  Any other reason that the Investigator considers makes the subject unsuitable to&#xD;
             participate.&#xD;
&#xD;
        Healthy Subjects (Cohorts 1, 2 &amp; 3)&#xD;
&#xD;
          -  Any chronic illness or clinically relevant abnormality identified on the screening&#xD;
             medical assessment, laboratory tests or ECG&#xD;
&#xD;
        Subjects with Asthma (Cohort 4)&#xD;
&#xD;
          -  Has ever had an episode of life-threatening asthma defined as respiratory arrest,&#xD;
             intubation for asthma, or ICU admission for asthma.&#xD;
&#xD;
          -  Presence of clinically significant diseases other than asthma, hyper-responsive&#xD;
             airways, seasonal allergic rhinitis or atopic diseases&#xD;
&#xD;
          -  Has experienced an acute asthma exacerbation in the 12 months prior to screening&#xD;
             requiring hospitalisation or accident and emergency treatment or management with&#xD;
             systemic or injectable steroids.&#xD;
&#xD;
          -  Has uncontrolled, or moderate to severe asthma based on PI assessment and/or use of&#xD;
             prohibited medications, or has required treatment with these therapies in the previous&#xD;
             12 weeks.&#xD;
&#xD;
          -  History or presence of any known conditions contraindicated for methacholine challenge&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Malcolm J Boyce, MBChB, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>cro</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hammersmith Medicines Research</name>
      <address>
        <city>London</city>
        <zip>NW10 7EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>December 20, 2017</last_update_submitted>
  <last_update_submitted_qc>December 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>PC-786</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/NCT03236233
org study id: PC_RSV_001
secondary id: 2016-000934-22
nct id: NCT03236233
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study investigates the safety, tolerability and pharmacokinetics of single and repeat
      doses of PC786.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants reporting one or more treatment-emergent adverse events (TEAE)
time frame: Baseline up to Week 12
measure: Number of participants who discontinue due to an adverse event (AE)
time frame: Baseline up to Week 12
measure: Number of participants who meet the markedly abnormal criteria for safety 12-lead ECG assessment at least once post dose
time frame: Baseline up to Week 12
measure: Number of participants who meet the markedly abnormal criteria for vital signs assessment at least once post dose
time frame: Baseline up to Week 12
measure: Number of participants who meet the markedly abnormal criteria for safety laboratory assessments at least once once post dose
time frame: Baseline up to Week 12
measure: Number of participants who meet the markedly abnormal criteria for safety spirometry assessment (FEV1 & FVC - measured together) at least once once post dose
time frame: Baseline up to Week 12
measure: Plasma concentration of PC786
time frame: Day 1: Pre-dose and at multiple time points (up to 10 days) post final dose
description: Blood levels of PC786 measured after dosing
measure: Mucosal lining fluid concentration of PC786
time frame: Cohort 1 - Day 1 = 3 samples; Day 2 = 2 samples; Day 3 = 1 sample. Cohorts 2 & 3 - Day 1 = 2 samples; Day 6 = 1 sample; Day 7 = 3 samples; Day 8 = 2 samples; Days 9 & 10 - 1 sample
description: PC786 concentration data in mucosal lining fluid measured after dosing
arm group label: Single dose - healthy subjects
arm group type: Experimental
arm group label: Repeat dose - healthy subjects
arm group type: Experimental
arm group label: Single dose - subjects with asthma
arm group type: Experimental
intervention type: Drug
intervention name: PC786 - Single doses
description: Safety and tolerability of single doses
arm group label: Single dose - healthy subjects
arm group label: Single dose - subjects with asthma
intervention type: Drug
intervention name: Placebo - Single doses
description: Safety and tolerability of single doses
arm group label: Single dose - healthy subjects
arm group label: Single dose - subjects with asthma
intervention type: Drug
intervention name: PC786 - Repeat doses
description: Safety and tolerability of repeat doses
arm group label: Repeat dose - healthy subjects
intervention type: Drug
intervention name: Placebo - Repeat doses
description: Safety and tolerability of repeat doses
arm group label: Repeat dose - healthy subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Malcolm J Boyce, MBChB, MD
role: Principal Investigator
affiliation: cro
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: PC-786