<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/NCT03756922</url>
  </required_header>
  <id_info>
    <org_study_id>FDL169-2018-10</org_study_id>
    <nct_id>NCT03756922</nct_id>
  </id_info>
  <brief_title>A DDI Study of FDL169 and FDL176 in Healthy Subjects</brief_title>
  <official_title>A Phase 1/2, Drug-Drug Interaction Study of FDL169 and FDL176 in Healthy Subjects and in Cystic Fibrosis Subjects Homozygous for the F508del-CFTR Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Flatley Discovery Lab LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Flatley Discovery Lab LLC</source>
  <oversight_info>
    <has_dmc>Yes</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>
      A DDI study to assess the safety, tolerability and pharmacokinetics of both; doses of FDL176&#xD;
      with and without co-administration of FDL169 and doses of FDL169 with and without&#xD;
      co-administration of FDL176.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, non-randomised study. Enrolment will be in two parallel and&#xD;
      independent parts. Part 1 will assess the safety, tolerability and pharmacokinetics of single&#xD;
      doses of FDL176 with and without co-administration of FDL169. Part 2 will assess the safety,&#xD;
      tolerability and pharmacokinetics of repeated doses of FDL169 with and without&#xD;
      co-administration of FDL176.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Business reasons&#xD;
  </why_stopped>
  <start_date type="Actual">November 27, 2018</start_date>
  <completion_date type="Anticipated">February 2020</completion_date>
  <primary_completion_date type="Anticipated">February 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Parallel for Part 1 and Part 2; Sequential for Part 3 and Part 4</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Parts 1, 2, and 3 are Open Label, while Part 4 is randomized and blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic parameters, Cmax</measure>
    <time_frame>Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks</time_frame>
    <description>Part 1: the pharmacokinetic parameters of FDL176 when co-administered with FDL169, compared to the pharmacokinetics of FDL176 alone. Part 2: the pharmacokinetics of FDL169 when co-administered with FDL176, compared to the pharmacokinetics of FDL169 alone. Part 3: PK when co-administered. Part 4: Safety and tolerability with multiple dose co-administration in CF subjects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks</time_frame>
    <description>Safety and tolerability when FDL176 and FDL169 are co-administrated,compared to FDL176 alone, and FDL169 alone, as determined by the incidence of adverse events (Aes) and serious adverse events (SAE)s. Part 4: Combination PK and CF transmembrane conductance regulator activity in CF subjects</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">78</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Part 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To receive a single dose of FDL176 on Day 1, followed by FDL169 TID for 28 days starting on Day 29; and another single dose of FDL176 on Day 42.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To receive FDL169 TID for 3 days from Day 1, followed by FDL176 QD for 19 days starting on Day 8; and FDL169 TID for 3 days from Day 24.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FDL169 and FDL176 for 28 days and 4 weeks of follow-up</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FDL169 and FDL176 for 28 days and 4 weeks of follow-up</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FDL169</intervention_name>
    <description>CFTR corrector</description>
    <arm_group_label>Part 1</arm_group_label>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_label>Part 3</arm_group_label>
    <arm_group_label>Part 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FDL176</intervention_name>
    <description>CFTR potentiator</description>
    <arm_group_label>Part 1</arm_group_label>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_label>Part 3</arm_group_label>
    <arm_group_label>Part 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males or non-pregnant, non-lactating healthy females&#xD;
&#xD;
          -  Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not&#xD;
             clinically significant by the investigator&#xD;
&#xD;
          -  Must agree to follow the study's contraception requirement&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior or ongoing medical condition, medical history, physical findings, ECG findings&#xD;
             or laboratory abnormality that, in the Investigator's (or delegate's) opinion, could&#xD;
             adversely affect the safety of the subject or would place the subject at increased&#xD;
             risk.&#xD;
&#xD;
          -  History of long QT syndrome and/or QT corrected according to Fridericia's formula&#xD;
             (QTcF) interval (&gt;450 msec) or QTcF &gt;450 msec at Screening or Day -1.&#xD;
&#xD;
          -  Presence or history of clinically significant allergy requiring treatment, as judged&#xD;
             by the investigator. Hayfever is allowed unless it is active.&#xD;
&#xD;
          -  Use of any prescription drugs within 14 days or 5 half-lives (whichever is longer)&#xD;
             before the first dose of IMP.&#xD;
&#xD;
          -  Use of any non-prescription drugs, including vitamins, herbal and dietary supplements&#xD;
             within 14 days or 5 half-lives (whichever is longer) before the first dose of IMP.&#xD;
&#xD;
          -  Use of any prescription and non-prescription medications that are strong inhibitors or&#xD;
             moderate inducers of cytochrome P450 3A, within 14 days or 5-half-lives (whichever is&#xD;
             longer) before the first dose of IMP. Use of any prescription and non-prescription&#xD;
             medications that are strong inducers of cytochrome P450 3A within 28 days before the&#xD;
             first dose of IMP.&#xD;
&#xD;
          -  Participation in another clinical trial involving receipt of an IMP within the past 90&#xD;
             days.&#xD;
&#xD;
          -  Prior exposure to FDL169 or FDL176&#xD;
&#xD;
          -  Alkaline phosphatase, aspartate aminotransferase and/or alanine aminotransferase &gt;1.5&#xD;
             x upper limit of normal (ULN) at screening.&#xD;
&#xD;
          -  Serum creatinine or total bilirubin &gt;1.5 x ULN (isolated bilirubin &gt;1.5 x ULN is&#xD;
             acceptable if bilirubin is fractionated and direct bilirubin is &lt;35%).&#xD;
&#xD;
          -  Abnormal renal function at screening, defined as estimated glomerular filtration rate&#xD;
             &lt;60 mL/min using the Modification of Diet in Renal Disease (MDRD) equation.&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV) or positive HIV, hepatitis B or&#xD;
             hepatitis C results at screening.&#xD;
&#xD;
          -  Positive urinary drugs of abuse screen at Screening or Day -1, or positive alcohol&#xD;
             breath test at Screening or Day -1. Consumption of alcohol within 24 h prior to&#xD;
             admission.&#xD;
&#xD;
          -  Consumption of any food or drink containing grapefruit, or Seville oranges (including&#xD;
             marmalade and fruit juices) for 14 days before the first dose of IMP.&#xD;
&#xD;
          -  Consumptions or foods containing poppy seeds or involvement in strenuous exercise for&#xD;
             3 days before admission.&#xD;
&#xD;
          -  Known hypersensitivity to any component of the formulation of FDL169 or FDL176.&#xD;
&#xD;
          -  Pregnant or nursing females.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study&#xD;
&#xD;
          -  Current smoking or use of tobacco products or substitutes.&#xD;
&#xD;
          -  Poor peripheral venous access.&#xD;
&#xD;
          -  Donation of ≥470 mL blood or loss of blood during surgery or due to trauma within 3&#xD;
             months prior to Day 1.&#xD;
&#xD;
          -  Plasma donation within 7 days prior to Day 1.&#xD;
&#xD;
          -  Failure to satisfy the Investigator of their fitness to participate for any other&#xD;
             reason.&#xD;
&#xD;
          -  Site staff, Sponsor staff or first degree family members of site or Sponsor.&#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>
  <location>
    <facility>
      <name>Celerion GB Ltd</name>
      <address>
        <city>Belfast</city>
        <zip>BT9 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>January 30, 2020</last_update_submitted>
  <last_update_submitted_qc>January 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <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>
  <!-- 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/NCT03756922
org study id: FDL169-2018-10
nct id: NCT03756922
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A DDI study to assess the safety, tolerability and pharmacokinetics of both; doses of FDL176
      with and without co-administration of FDL169 and doses of FDL169 with and without
      co-administration of FDL176.
This is an open-label, non-randomised study. Enrolment will be in two parallel and
      independent parts. Part 1 will assess the safety, tolerability and pharmacokinetics of single
      doses of FDL176 with and without co-administration of FDL169. Part 2 will assess the safety,
      tolerability and pharmacokinetics of repeated doses of FDL169 with and without
      co-administration of FDL176.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Parallel for Part 1 and Part 2; Sequential for Part 3 and Part 4
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Parts 1, 2, and 3 are Open Label, while Part 4 is randomized and blinded
measure: Pharmacokinetic parameters, Cmax
time frame: Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks
description: Part 1: the pharmacokinetic parameters of FDL176 when co-administered with FDL169, compared to the pharmacokinetics of FDL176 alone. Part 2: the pharmacokinetics of FDL169 when co-administered with FDL176, compared to the pharmacokinetics of FDL169 alone. Part 3: PK when co-administered. Part 4: Safety and tolerability with multiple dose co-administration in CF subjects
measure: Incidence of Treatment-Emergent Adverse Events
time frame: Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks
description: Safety and tolerability when FDL176 and FDL169 are co-administrated,compared to FDL176 alone, and FDL169 alone, as determined by the incidence of adverse events (Aes) and serious adverse events (SAE)s. Part 4: Combination PK and CF transmembrane conductance regulator activity in CF subjects
arm group label: Part 1
arm group type: Experimental
description: To receive a single dose of FDL176 on Day 1, followed by FDL169 TID for 28 days starting on Day 29; and another single dose of FDL176 on Day 42.
arm group label: Part 2
arm group type: Experimental
description: To receive FDL169 TID for 3 days from Day 1, followed by FDL176 QD for 19 days starting on Day 8; and FDL169 TID for 3 days from Day 24.
arm group label: Part 3
arm group type: Experimental
description: FDL169 and FDL176 for 28 days and 4 weeks of follow-up
arm group label: Part 4
arm group type: Experimental
description: FDL169 and FDL176 for 28 days and 4 weeks of follow-up
intervention type: Drug
intervention name: FDL169
description: CFTR corrector
arm group label: Part 1
arm group label: Part 2
arm group label: Part 3
arm group label: Part 4
intervention type: Drug
intervention name: FDL176
description: CFTR potentiator
arm group label: Part 1
arm group label: Part 2
arm group label: Part 3
arm group label: Part 4
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis