<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/NCT03251092</url>
  </required_header>
  <id_info>
    <org_study_id>PTI-808-01</org_study_id>
    <nct_id>NCT03251092</nct_id>
  </id_info>
  <brief_title>Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis</brief_title>
  <official_title>A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808 in Healthy Adult Subjects and in Adults 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>
      Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),&#xD;
      multiple ascending dose (MAD), and Food Effect (FE) treatment groups.&#xD;
&#xD;
      The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy&#xD;
      adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and&#xD;
      will be followed for 7 days post dose. A safety review committee (SRC) will convene after the&#xD;
      completion of each cohort to evaluate safety and pharmacokinetic (PK) data.&#xD;
&#xD;
      Following the conclusion of the respective SAD level dose groups and after sufficient review&#xD;
      of study data and approval by the SRC, a second set of healthy adult subjects will&#xD;
      participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3&#xD;
      ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or&#xD;
      placebo daily for 7 days and will be followed for 7 days after receiving the last dose.&#xD;
&#xD;
      Also following the conclusion of the respective SAD level dose groups, healthy adult subjects&#xD;
      will participate in the FE treatment group.&#xD;
&#xD;
      Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of&#xD;
      PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive&#xD;
      days.&#xD;
&#xD;
      Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group&#xD;
      consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and&#xD;
      PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 +&#xD;
      PTI-801 + PTI-428 administered daily for 14 consecutive days.&#xD;
&#xD;
      Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects&#xD;
      will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching&#xD;
      placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),&#xD;
      multiple ascending dose (MAD), and Food Effect (FE) treatment groups.&#xD;
&#xD;
      The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy&#xD;
      adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and&#xD;
      will be followed for 7 days post dose.&#xD;
&#xD;
      The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be&#xD;
      randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7&#xD;
      days after receiving the last dose.&#xD;
&#xD;
      Following the conclusion of the respective SAD level dose groups the food effect portion of&#xD;
      the study will be initiated and subjects will be randomized to receive an initial single dose&#xD;
      of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an&#xD;
      overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal&#xD;
      (fed group). After a 10 day washout period, subjects will cross over to the opposite group&#xD;
      and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following&#xD;
      dosing.&#xD;
&#xD;
      Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of&#xD;
      PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive&#xD;
      days.&#xD;
&#xD;
      Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK&#xD;
      of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects&#xD;
      will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo&#xD;
      co-administered with PTI-801+PTI-428 or matching placebos.&#xD;
&#xD;
      Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808&#xD;
      co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF&#xD;
      subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the&#xD;
      F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808&#xD;
      co-administered with PTI-801 with or without PTI-428 versus matching placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2017</start_date>
  <completion_date type="Actual">December 23, 2019</completion_date>
  <primary_completion_date type="Actual">December 23, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1 SAD and MAD: Adverse Events</measure>
    <time_frame>Baseline to up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and MAD: Physical Exams</measure>
    <time_frame>Baseline to up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs</measure>
    <time_frame>Baseline to up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and MAD: ECGs</measure>
    <time_frame>Baseline to up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs</measure>
    <time_frame>Baseline to up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and FE: terminal half life</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>Apparent terminal half-life (t1/2) of single oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and FE : Tmax</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>Time to reach maximum plasma concentration (Tmax) of single oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and FE: Cmax</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>Maximum plasma concentration (Cmax) of single oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD : AUC</measure>
    <time_frame>Through 24 hours post dose</time_frame>
    <description>Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and FE: AUC0</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 SAD and FE: AUC0-inf</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>AUC from time 0 to infinity (AUC0-inf) of single dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: t1/2</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>t1/2 of multiple oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: Tmax</measure>
    <time_frame>Through 72 hours post dose</time_frame>
    <description>Tmax of multiple oral doses</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: Cmax</measure>
    <time_frame>Through 72 hours post last dose</time_frame>
    <description>Cmax of multiple oral doses</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: AUC0-24</measure>
    <time_frame>Through 24 hours post last dose</time_frame>
    <description>AUC0-24 of multiple oral dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: AUC0-last</measure>
    <time_frame>Through 72 hours post last dose</time_frame>
    <description>AUC0-last of multiple oral doses</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: Urine</measure>
    <time_frame>Through 24 hours post last dose</time_frame>
    <description>Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 MAD: CLR</measure>
    <time_frame>Through 24 hours post dose</time_frame>
    <description>Renal clearance (CLR) of multiple oral doses</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Physical Exams</measure>
    <time_frame>Baseline up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: ECGs</measure>
    <time_frame>Baseline up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Safety Labs</measure>
    <time_frame>Baseline up to 14 days</time_frame>
    <description>Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Vitals Signs</measure>
    <time_frame>Baseline up to 14 days</time_frame>
    <description>Measure by number of subjects who experience potential clinically significant changes in vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3 CF: Physical Exams</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3 CF: ECGs</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3 CF: Safety Labs</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3 CF: Vital Signs</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>Measured by number of subjects who experience potential clinically significant changes in vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 4 CF: Physical Exams</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 4 CF: ECGs</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 4 CF: Safety Labs</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 4 CF: Vital Signs</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 22</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 22</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428</measure>
    <time_frame>Day 1 through Day 22</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3 CF: FEV1</measure>
    <time_frame>Baseline through Day 28</time_frame>
    <description>Change in forced expiratory volume in one second (FEV1) over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 4 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428</measure>
    <time_frame>Day 1 through Day 28</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428</measure>
    <time_frame>Day 1 through 28</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 4 CF: AUC0-last of multiple oral doses when PTI 808 + PTI 801 is coadministered with or without PTI 428 in adults with CF</measure>
    <time_frame>Day 1 through 28</time_frame>
    <description>Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or without PTI 428 in adults with CF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 4 CF: FEV1</measure>
    <time_frame>Baseline through Day 42</time_frame>
    <description>Change in forced expiratory volume in one second (FEV1) over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 4 CF Sweat Chloride</measure>
    <time_frame>Baseline through Day 42</time_frame>
    <description>Change in sweat chloride concentrations over time</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Part 2 Nasal biomarker</measure>
    <time_frame>Baseline up to 14 days</time_frame>
    <description>change in nasal epithelial mRNA and protein over time</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 3 CF Sweat Chloride</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>Change in sweat chloride concentrations over time</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 3 CF Nasal biomarker</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>Change in nasal epithelial mRNA and protein expression over time</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 4 CF Weight and BMI</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Change in weight and BMI over time</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 4 CF Blood Glucose</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Change in blood glucose over time</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 4 CF disease-specific health related quality of life</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Change in disease-specific health related quality of life over time</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 4 CF Nasal biomarker</measure>
    <time_frame>Baseline up to 42 days</time_frame>
    <description>Change in nasal epithelial mRNA and protein expression over time</description>
  </other_outcome>
  <number_of_arms>15</number_of_arms>
  <enrollment type="Actual">179</enrollment>
  <condition>Healthy Volunteer - Complete</condition>
  <condition>Cystic Fibrosis - Complete</condition>
  <arm_group>
    <arm_group_label>SAD PTI-808 Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD PTI-808 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD PTI-808 Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD PTI-808 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FE PTI-808 Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FE PTI-808 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 PTI-808 + PTI-801 + PTI-428 Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 matching Placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In all three cohorts in part 2, subjects will be randomized to active drug or placebo. The placebo arm for all cohorts consists of placebo capsules matching PTI-808+PTI-801+PTI-428.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 CF MAD PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In all cohorts in Part 3, subjects will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In cohorts 3 &amp; 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In cohorts 3 &amp; 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In cohorts 3 &amp; 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTI-808</intervention_name>
    <description>Active</description>
    <arm_group_label>FE PTI-808 Active</arm_group_label>
    <arm_group_label>MAD PTI-808 Active</arm_group_label>
    <arm_group_label>Part 2 PTI-808 + PTI-801 + PTI-428 Active</arm_group_label>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo</arm_group_label>
    <arm_group_label>Part 3 CF MAD PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo</arm_group_label>
    <arm_group_label>SAD PTI-808 Active</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>FE PTI-808 Placebo</arm_group_label>
    <arm_group_label>MAD PTI-808 Placebo</arm_group_label>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo</arm_group_label>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo</arm_group_label>
    <arm_group_label>Part 2 matching Placebos</arm_group_label>
    <arm_group_label>Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo</arm_group_label>
    <arm_group_label>Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo</arm_group_label>
    <arm_group_label>SAD PTI-808 Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTI-428</intervention_name>
    <description>Active</description>
    <arm_group_label>Part 2 PTI-808 + PTI-801 + PTI-428 Active</arm_group_label>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo</arm_group_label>
    <arm_group_label>Part 3 CF MAD PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTI-801</intervention_name>
    <description>Active</description>
    <arm_group_label>Part 2 PTI-808 + PTI-801 + PTI-428 Active</arm_group_label>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo</arm_group_label>
    <arm_group_label>Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo</arm_group_label>
    <arm_group_label>Part 3 CF MAD PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428</arm_group_label>
    <arm_group_label>Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Part 1 and Part 2 Inclusion Criteria:&#xD;
&#xD;
          1. Adults aged 18 to 55 years old, inclusive, at the time of informed consent&#xD;
&#xD;
          2. Body mass index ≥18 and &lt;30 kg/m2&#xD;
&#xD;
          3. Subject must be a non-smoker and non-tobacco user for a minimum of 30 days prior to&#xD;
             screening and for the duration of the study.&#xD;
&#xD;
          4. Subject understands the full nature and purpose of the study, including possible risks&#xD;
             and side effects, and is willing and able to comply with all compulsory study&#xD;
             procedures and provides informed consent/permission prior to any study procedures&#xD;
             being performed.&#xD;
&#xD;
          5. Females of childbearing potential and males capable of fathering a child must meet the&#xD;
             contraception requirements&#xD;
&#xD;
        Part 1 &amp; Part 2 Exclusion Criteria:&#xD;
&#xD;
          1. History or current evidence of any clinically significant cardiac, endocrinologic,&#xD;
             hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic,&#xD;
             dermatologic, psychiatric, renal, or other major disease, as determined by the&#xD;
             investigator&#xD;
&#xD;
          2. Prolonged QT interval with Fridericia's correction &gt;450 msec at screening&#xD;
&#xD;
          3. Abnormal liver function as defined by aspartate transaminase (AST), alanine&#xD;
             transaminase (ALT), or bilirubin &gt;1.5× the upper limit of the normal range&#xD;
&#xD;
          4. Abnormal renal function at screening defined as creatinine clearance &lt;90 mL/min using&#xD;
             the Cockroft-Gault equation&#xD;
&#xD;
          5. Clinically significant screening results that would exclude subject from the study&#xD;
             (e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by&#xD;
             the investigator&#xD;
&#xD;
          6. Participation in another clinical study or treatment with an investigational agent&#xD;
             within 30 days or five half-lives, whichever is longer, prior to Study Day 1&#xD;
&#xD;
          7. History of cancer within the past 5 years (excluding non-melanoma skin cancer)&#xD;
&#xD;
          8. History or current evidence of alcohol or drug abuse or dependence within 12 months of&#xD;
             screening as determined by the investigator&#xD;
&#xD;
          9. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine&#xD;
             cotinine is the detection mechanism for nicotine], opiates, barbiturates,&#xD;
             amphetamines, and benzodiazepines) or positive alcohol test at screening&#xD;
&#xD;
         10. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface&#xD;
             antigen (HBsAg), or hepatitis C virus antibody (HCVAb)&#xD;
&#xD;
         11. Clinically significant infection within 3 months of screening as determined by the&#xD;
             investigator&#xD;
&#xD;
         12. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or&#xD;
             any components thereof&#xD;
&#xD;
         13. Has donated blood within 3 months of screening or plans to donate blood within 3&#xD;
             months of study completion&#xD;
&#xD;
         14. Pregnant or nursing women&#xD;
&#xD;
         15. Any conditions that, in the opinion of the investigator, would make the subject&#xD;
             unsuitable for enrollment or could interfere with the subject's participation in or&#xD;
             completion of the study&#xD;
&#xD;
         16. Use of prohibited medications within 14 days prior to dosing of study drug&#xD;
&#xD;
        Part 3 CF Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed diagnosis of CF with the F508del/F508del genotype&#xD;
&#xD;
          2. Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive&#xD;
&#xD;
          3. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening&#xD;
&#xD;
        Part 3 CF Exclusion Criteria:&#xD;
&#xD;
          1. Participation in another clinical trial or treatment with an investigational agent&#xD;
             within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1&#xD;
&#xD;
          2. History of cancer within the past 5 years (excluding cervical cancer in situ with&#xD;
             curative therapy for at least one year prior to screening and non-melanoma skin&#xD;
             cancer)&#xD;
&#xD;
          3. History of organ transplantation&#xD;
&#xD;
          4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically&#xD;
             significant infection or illness (as determined by the investigator) requiring an&#xD;
             increase or addition of medication, such as antibiotics or corticosteroids, within 14&#xD;
             days of Day 1&#xD;
&#xD;
          5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,&#xD;
             azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy&#xD;
             (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1&#xD;
&#xD;
          6. History or current evidence of alcohol or drug abuse or dependence within 12 months of&#xD;
             screening as determined by the investigator&#xD;
&#xD;
          7. Pregnant or nursing women&#xD;
&#xD;
          8. Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of&#xD;
             study drugs&#xD;
&#xD;
        Part 4 CF Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed diagnosis of CF with either the F508del CFTR homozygous genotype on record&#xD;
             or for heterozygote subjects, only one copy of the F508del CFTR mutation on record&#xD;
&#xD;
          2. Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive&#xD;
&#xD;
          3. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening&#xD;
&#xD;
        Part 4 CF Exclusion Criteria:&#xD;
&#xD;
          1. Participation in another clinical trial or treatment with an investigational agent&#xD;
             within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1&#xD;
&#xD;
          2. History of cancer within the past 5 years (excluding cervical cancer in situ with&#xD;
             curative therapy for at least one year prior to screening and non-melanoma skin&#xD;
             cancer)&#xD;
&#xD;
          3. History of organ transplantation&#xD;
&#xD;
          4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically&#xD;
             significant infection or illness (as determined by the investigator) requiring an&#xD;
             increase or addition of medication, such as antibiotics or corticosteroids, within 28&#xD;
             days of Day 1&#xD;
&#xD;
          5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,&#xD;
             azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy&#xD;
             (excluding pancreatic enzyme replacement therapy) within 28 days of Day 1&#xD;
&#xD;
          6. History or current evidence of alcohol or drug abuse or dependence within 12 months of&#xD;
             screening as determined by the investigator&#xD;
&#xD;
          7. Pregnant or nursing women&#xD;
&#xD;
          8. Currently taking or has taken a CFTR modulator within 14 days prior to the screening&#xD;
             visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cassandra Key, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ICON Early Phase Services (Parts 1 &amp; 2)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Patrick Flume, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina (Parts 3 &amp; 4)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner University of Arizona Medical Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Florida Pulmonary Group</name>
      <address>
        <city>Altamonte Springs</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Children's Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Medicine, University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harper University Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Billings Clinic</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27517</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICON Early Phase Services</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>Lambton</city>
        <state>New South Wales</state>
        <zip>2305</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair ziekenhuis Brussel</name>
      <address>
        <city>Brussels</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z1Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval</name>
      <address>
        <city>Québec</city>
        <zip>G1V4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Copenhagen Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pasteur</name>
      <address>
        <city>Nice</city>
        <state>Alpes-Maritimes</state>
        <zip>06001</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Haut Lévêque</name>
      <address>
        <city>Pessac</city>
        <state>Gironde</state>
        <zip>33600</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Guillaume-et-René-Laennec</name>
      <address>
        <city>Nantes</city>
        <state>Loire-Atlantique</state>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Maison Blanche Maladies respiratoires et allergologie</name>
      <address>
        <city>Reims</city>
        <state>Marne</state>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Cologne</name>
      <address>
        <city>Cologne</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <zip>45239</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der J.W. Goethe Universität</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum des Universität München</name>
      <address>
        <city>München</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland Clinical Studies Ltd.</name>
      <address>
        <city>Grafton</city>
        <state>Auckland</state>
        <zip>1010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Devon and Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <state>Devon</state>
        <zip>EX2 5DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <state>Scotland</state>
        <zip>EH42XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Heartlands Hospital</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B9 5SS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Belfast City Hospital</name>
      <address>
        <city>Belfast</city>
        <zip>BT9 7AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <zip>SE59RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>New Zealand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>April 20, 2020</last_update_submitted>
  <last_update_submitted_qc>April 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 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>
  <!-- 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/NCT03251092
org study id: PTI-808-01
nct id: NCT03251092
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),
      multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

      The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy
      adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and
      will be followed for 7 days post dose. A safety review committee (SRC) will convene after the
      completion of each cohort to evaluate safety and pharmacokinetic (PK) data.

      Following the conclusion of the respective SAD level dose groups and after sufficient review
      of study data and approval by the SRC, a second set of healthy adult subjects will
      participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3
      ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or
      placebo daily for 7 days and will be followed for 7 days after receiving the last dose.

      Also following the conclusion of the respective SAD level dose groups, healthy adult subjects
      will participate in the FE treatment group.

      Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of
      PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive
      days.

      Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group
      consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and
      PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 +
      PTI-801 + PTI-428 administered daily for 14 consecutive days.

      Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects
      will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching
      placebo.
Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),
      multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

      The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy
      adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and
      will be followed for 7 days post dose.

      The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be
      randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7
      days after receiving the last dose.

      Following the conclusion of the respective SAD level dose groups the food effect portion of
      the study will be initiated and subjects will be randomized to receive an initial single dose
      of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an
      overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal
      (fed group). After a 10 day washout period, subjects will cross over to the opposite group
      and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following
      dosing.

      Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of
      PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive
      days.

      Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK
      of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects
      will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo
      co-administered with PTI-801+PTI-428 or matching placebos.

      Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808
      co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF
      subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the
      F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808
      co-administered with PTI-801 with or without PTI-428 versus matching placebo.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Part 1 SAD and MAD: Adverse Events
time frame: Baseline to up to 14 days
description: Safety and tolerability measure by number of subjects who experience adverse events
measure: Part 1 SAD and MAD: Physical Exams
time frame: Baseline to up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
measure: Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in vital signs
time frame: Baseline to up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
measure: Part 1 SAD and MAD: ECGs
time frame: Baseline to up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
measure: Part 1 SAD and MAD: The number of subjects who experience potential clinically significant changes in safety labs
time frame: Baseline to up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
measure: Part 1 SAD and FE: terminal half life
time frame: Through 72 hours post dose
description: Apparent terminal half-life (t1/2) of single oral dose
measure: Part 1 SAD and FE : Tmax
time frame: Through 72 hours post dose
description: Time to reach maximum plasma concentration (Tmax) of single oral dose
measure: Part 1 SAD and FE: Cmax
time frame: Through 72 hours post dose
description: Maximum plasma concentration (Cmax) of single oral dose
measure: Part 1 SAD : AUC
time frame: Through 24 hours post dose
description: Area under the concentration-time curve from time 0 to 24 hours post dose (AUC 0-24) of single oral dose
measure: Part 1 SAD and FE: AUC0
time frame: Through 72 hours post dose
description: AUC from time 0 to time of last measurable concentration (AUC0-last) of single oral dose
measure: Part 1 SAD and FE: AUC0-inf
time frame: Through 72 hours post dose
description: AUC from time 0 to infinity (AUC0-inf) of single dose
measure: Part 1 MAD: t1/2
time frame: Through 72 hours post dose
description: t1/2 of multiple oral dose
measure: Part 1 MAD: Tmax
time frame: Through 72 hours post dose
description: Tmax of multiple oral doses
measure: Part 1 MAD: Cmax
time frame: Through 72 hours post last dose
description: Cmax of multiple oral doses
measure: Part 1 MAD: AUC0-24
time frame: Through 24 hours post last dose
description: AUC0-24 of multiple oral dose
measure: Part 1 MAD: AUC0-last
time frame: Through 72 hours post last dose
description: AUC0-last of multiple oral doses
measure: Part 1 MAD: Urine
time frame: Through 24 hours post last dose
description: Cumulative amount of PTI-808 excreted unchanged in urine (Ae) as appropriate of multiple oral doses
measure: Part 1 MAD: CLR
time frame: Through 24 hours post dose
description: Renal clearance (CLR) of multiple oral doses
measure: Part 2: Physical Exams
time frame: Baseline up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical examinations
measure: Part 2: ECGs
time frame: Baseline up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
measure: Part 2: Safety Labs
time frame: Baseline up to 14 days
description: Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
measure: Part 2: Vitals Signs
time frame: Baseline up to 14 days
description: Measure by number of subjects who experience potential clinically significant changes in vital signs
measure: Part 3 CF: Physical Exams
time frame: Baseline up to 28 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
measure: Part 3 CF: ECGs
time frame: Baseline up to 28 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
measure: Part 3 CF: Safety Labs
time frame: Baseline up to 28 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
measure: Part 3 CF: Vital Signs
time frame: Baseline up to 28 days
description: Measured by number of subjects who experience potential clinically significant changes in vital signs
measure: Part 4 CF: Physical Exams
time frame: Baseline up to 42 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
measure: Part 4 CF: ECGs
time frame: Baseline up to 42 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in ECGs
measure: Part 4 CF: Safety Labs
time frame: Baseline up to 42 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in safety labs
measure: Part 4 CF: Vital Signs
time frame: Baseline up to 42 days
description: Safety and tolerability measured by number of subjects who experience potential clinically significant changes in physical examinations
measure: Part 2: Apparent terminal half life (t1/2) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 10
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
measure: Part 2: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 10
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
measure: Part 2: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 10
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
measure: Part 2: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 10
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
measure: Part 2: AUC from time 0 to infinity (AUC0-inf) of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 10
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in healthy adults
measure: Part 3 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 22
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
measure: Part 3 CF: Maximum plasma concentration (Cmax) of multiple oral doses PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 22
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
measure: Part 3 CF: AUC0-last of multiple oral doses when PTI 808 is co administered with PTI 801 and PTI 428
time frame: Day 1 through Day 22
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 is co administered with PTI 801 and PTI 428 in adults with CF
measure: Part 3 CF: FEV1
time frame: Baseline through Day 28
description: Change in forced expiratory volume in one second (FEV1) over time
measure: Part 4 CF: Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
time frame: Day 1 through Day 28
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF
measure: Part 4 CF: Maximum plasma concentration (Cmax) of multiple oral doses of PTI 808 + PTI 801 co-administered with or without PTI 428
time frame: Day 1 through 28
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or with out PTI 428 in adults with CF
measure: Part 4 CF: AUC0-last of multiple oral doses when PTI 808 + PTI 801 is coadministered with or without PTI 428 in adults with CF
time frame: Day 1 through 28
description: Evaluate the PK profile of PTI 808, PTI 801, and PTI 428 when PTI 808 + PTI 801 is co administered with or without PTI 428 in adults with CF
measure: Part 4 CF: FEV1
time frame: Baseline through Day 42
description: Change in forced expiratory volume in one second (FEV1) over time
measure: Part 4 CF Sweat Chloride
time frame: Baseline through Day 42
description: Change in sweat chloride concentrations over time
measure: Part 2 Nasal biomarker
time frame: Baseline up to 14 days
description: change in nasal epithelial mRNA and protein over time
measure: Part 3 CF Sweat Chloride
time frame: Baseline up to 28 days
description: Change in sweat chloride concentrations over time
measure: Part 3 CF Nasal biomarker
time frame: Baseline up to 28 days
description: Change in nasal epithelial mRNA and protein expression over time
measure: Part 4 CF Weight and BMI
time frame: Baseline up to 42 days
description: Change in weight and BMI over time
measure: Part 4 CF Blood Glucose
time frame: Baseline up to 42 days
description: Change in blood glucose over time
measure: Part 4 CF disease-specific health related quality of life
time frame: Baseline up to 42 days
description: Change in disease-specific health related quality of life over time
measure: Part 4 CF Nasal biomarker
time frame: Baseline up to 42 days
description: Change in nasal epithelial mRNA and protein expression over time
arm group label: SAD PTI-808 Active
arm group type: Active Comparator
description: Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
arm group label: SAD PTI-808 Placebo
arm group type: Placebo Comparator
description: Three cohorts of SAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
arm group label: MAD PTI-808 Active
arm group type: Active Comparator
description: Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
arm group label: MAD PTI-808 Placebo
arm group type: Placebo Comparator
description: Three cohorts of MAD are planned for evaluation where subjects will be randomized to PTI-808 or placebo.
arm group label: FE PTI-808 Active
arm group type: Active Comparator
description: Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.
arm group label: FE PTI-808 Placebo
arm group type: Placebo Comparator
description: Subjects will be randomized to Fed or Fasted on Days 1 and 12. Follow up visits will occur 7 days post Day 12 dose.
arm group label: Part 2 PTI-808 + PTI-801 + PTI-428 Active
arm group type: Experimental
description: One cohort is planned where subjects will be randomized to either the triple active arm (dosed with PTI 808+PTI 801+PTI 428) OR placebo arm.
arm group label: Part 2 matching Placebos
arm group type: Placebo Comparator
description: In all three cohorts in part 2, subjects will be randomized to active drug or placebo. The placebo arm for all cohorts consists of placebo capsules matching PTI-808+PTI-801+PTI-428.
arm group label: Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo
arm group type: Experimental
description: One cohort is planned where subjects are randomized to either 808 placebo + dual active arm (dosed with placebo matching PTI 808 plus PTI 801 + PTI 428) OR placebo arm.
arm group label: Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo
arm group type: Active Comparator
description: One cohort is planned where subjects are randomized to either 428 placebo + dual active arm (dosed with placebo matching PTI 428 plus PTI 808 and PTI 801) OR placebo arm.
arm group label: Part 3 CF MAD PTI-808 + PTI-801 + PTI-428
arm group type: Active Comparator
description: In all cohorts in Part 3, subjects will be will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28.
arm group label: Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo
arm group type: Placebo Comparator
description: In all cohorts in Part 3, subjects will be randomized to receive 7 days of PTI-808 or placebo followed by 14 days of co-administration of PTI-808+PTI-801+PTI-428 or matching placebos. A follow-up will occur on Day 28.
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428
arm group type: Active Comparator
description: In cohorts 3 & 4 subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo
arm group type: Active Comparator
description: In cohorts 3 & 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.
arm group label: Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo
arm group type: Placebo Comparator
description: In cohorts 3 & 4, subjects will be randomized to receive PTI-808 + PTI-801 with or without PTI-428 or matching placebos. A follow-up will occur on Day 42.
intervention type: Drug
intervention name: PTI-808
description: Active
arm group label: FE PTI-808 Active
arm group label: MAD PTI-808 Active
arm group label: Part 2 PTI-808 + PTI-801 + PTI-428 Active
arm group label: Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo
arm group label: Part 3 CF MAD PTI-808 + PTI-801 + PTI-428
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo
arm group label: SAD PTI-808 Active
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: FE PTI-808 Placebo
arm group label: MAD PTI-808 Placebo
arm group label: Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo
arm group label: Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo
arm group label: Part 2 matching Placebos
arm group label: Part 3 CF MAD PTI-808 placebo+PTI-801 placebo+PTI-428 placebo
arm group label: Part 4 CF PTI-808 placebo + PTI-801 placebo + PTI-428 placebo
arm group label: SAD PTI-808 Placebo
intervention type: Drug
intervention name: PTI-428
description: Active
arm group label: Part 2 PTI-808 + PTI-801 + PTI-428 Active
arm group label: Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo
arm group label: Part 3 CF MAD PTI-808 + PTI-801 + PTI-428
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428
intervention type: Drug
intervention name: PTI-801
description: Active
arm group label: Part 2 PTI-808 + PTI-801 + PTI-428 Active
arm group label: Part 2 dual active arm PTI-801+PTI-428+ PTI-808 placebo
arm group label: Part 2 dual active arm PTI-801+PTI-808+PTI-428 placebo
arm group label: Part 3 CF MAD PTI-808 + PTI-801 + PTI-428
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428
arm group label: Part 4 CF PTI-808 + PTI-801 + PTI-428 placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cassandra Key, MD
role: Principal Investigator
affiliation: ICON Early Phase Services (Parts 1 & 2)
last name: Patrick Flume, MD
role: Principal Investigator
affiliation: Medical University of South Carolina (Parts 3 & 4)
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country: Australia
country: Belgium
country: Canada
country: Denmark
country: France
country: Germany
country: New Zealand
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis