<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/NCT03258424</url>
  </required_header>
  <id_info>
    <org_study_id>PTI-428-05</org_study_id>
    <nct_id>NCT03258424</nct_id>
  </id_info>
  <brief_title>Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis on KALYDECO® as Background Therapy</brief_title>
  <official_title>A Phase I, Randomized, Placebo-Controlled, Study Designed to Assess the Safety, Tolerability, and Pharmacokinetics of PTI-428 in Subjects With Cystic Fibrosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Proteostasis Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Proteostasis Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial will consist of a single treatment group enrolling adult subjects with CF on&#xD;
      background therapy with KALYDECO®. Approximately 16 subjects will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The single treatment group will enroll adult subjects with CF currently on stable KALYDECO®&#xD;
      background therapy for a minimum of 3 months at the time of randomization. Subjects will be&#xD;
      randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a&#xD;
      total of 14 Days. The subjects will continue treatment with KALYDECO® throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 28, 2017</start_date>
  <completion_date type="Actual">October 3, 2018</completion_date>
  <primary_completion_date type="Actual">October 3, 2018</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>Safety and tolerability as assessed by adverse events, safety labs, electrocardiograms (ECGs), physical examinations, and vital signs</measure>
    <time_frame>Baseline through Day 21</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>t1/2 of multiple oral doses</measure>
    <time_frame>Baseline through Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of multiple oral doses</measure>
    <time_frame>Baseline through Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of multiple oral doses</measure>
    <time_frame>Baseline through Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t of multiple oral doses</measure>
    <time_frame>Baseline through Day 14</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in nasal epithelial mRNA and protein expression over time</measure>
    <time_frame>Baseline through Day 21</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in sweat chloride over time</measure>
    <time_frame>Baseline through Day 21</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in FEV1 over time</measure>
    <time_frame>Baseline through Day 21</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in weight over time</measure>
    <time_frame>Baseline through Day 21</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>PTI-428</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will receive once daily dosing of PTI-428 or placebo for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive once daily dosing of PTI-428 or placebo for 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTI-428</intervention_name>
    <description>PTI-428 or placebo will be given QD for 14 days.</description>
    <arm_group_label>PTI-428</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>PTI-428 or placebo will be given QD for 14 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of CF.&#xD;
&#xD;
          -  Stable on Kalydeco dosing for both label indication and per label dosing for a minimum&#xD;
             of 3 months at the time of randomization&#xD;
&#xD;
          -  Forced expiratory volume in 1 second (FEV1) 40-90% predicted.&#xD;
&#xD;
          -  Non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for&#xD;
             the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in another clinical trial or treatment with an investigational agent&#xD;
             within 30 days or 5 half-lives, whichever is longer, prior to Study Day 1.&#xD;
&#xD;
          -  History of cancer within the past five years (excluding cervical CIS with curative&#xD;
             therapy for at least one year prior to screening and non-melanoma skin cancer).&#xD;
&#xD;
          -  History of organ transplantation.&#xD;
&#xD;
          -  Any sinopulmonary infection or CF exacerbation requiring a change or addition of&#xD;
             medication (including antibiotics) within 1 month of Study Day 1 or any other&#xD;
             clinically significant infection as determined by the investigator within 1 month of&#xD;
             Day 1.&#xD;
&#xD;
          -  History of alcohol or drug abuse or dependence within 12 months of screening as&#xD;
             determined by the Investigator.&#xD;
&#xD;
          -  Male and female of child-bearing potential, unless they are using highly effective&#xD;
             methods of contraception during participation in the clinical study and for 4 weeks&#xD;
             after termination from study.&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Celerion</name>
      <address>
        <city>Belfast</city>
        <zip>BT9 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medicines Evaluation Unit</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>March 24, 2020</last_update_submitted>
  <last_update_submitted_qc>March 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 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>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT03258424
org study id: PTI-428-05
nct id: NCT03258424
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The trial will consist of a single treatment group enrolling adult subjects with CF on
      background therapy with KALYDECO®. Approximately 16 subjects will be enrolled.
The single treatment group will enroll adult subjects with CF currently on stable KALYDECO®
      background therapy for a minimum of 3 months at the time of randomization. Subjects will be
      randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a
      total of 14 Days. The subjects will continue treatment with KALYDECO® throughout the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety and tolerability as assessed by adverse events, safety labs, electrocardiograms (ECGs), physical examinations, and vital signs
time frame: Baseline through Day 21
measure: t1/2 of multiple oral doses
time frame: Baseline through Day 14
measure: Tmax of multiple oral doses
time frame: Baseline through Day 14
measure: Cmax of multiple oral doses
time frame: Baseline through Day 14
measure: AUC0-t of multiple oral doses
time frame: Baseline through Day 14
measure: Change in nasal epithelial mRNA and protein expression over time
time frame: Baseline through Day 21
measure: Change in sweat chloride over time
time frame: Baseline through Day 21
measure: Change in FEV1 over time
time frame: Baseline through Day 21
measure: Change in weight over time
time frame: Baseline through Day 21
arm group label: PTI-428
arm group type: Active Comparator
description: Subjects will receive once daily dosing of PTI-428 or placebo for 14 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will receive once daily dosing of PTI-428 or placebo for 14 days.
intervention type: Drug
intervention name: PTI-428
description: PTI-428 or placebo will be given QD for 14 days.
arm group label: PTI-428
intervention type: Drug
intervention name: Placebo
description: PTI-428 or placebo will be given QD for 14 days.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
sharing ipd: Yes