<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/NCT03815695</url>
  </required_header>
  <id_info>
    <org_study_id>4202-HVS-101</org_study_id>
    <nct_id>NCT03815695</nct_id>
  </id_info>
  <brief_title>A SAD/MAD to Assess the Safety, PK/PD of FT-4202 in Healthy Volunteers and Sickle Cell Disease Patients</brief_title>
  <official_title>A Randomized, Placebo-controlled, Double Blind, Single Ascending and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of FT-4202 in Healthy Volunteers and Sickle Cell Disease Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medpace, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Novo Nordisk A/S</source>
  <oversight_info>
    <has_dmc>No</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>
      FT-4202 is an oral small-molecule agonist of pyruvate kinase red blood cell isozyme (PKR)&#xD;
      being developed for the treatment of hemolytic anemias. This initial study will characterize&#xD;
      the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of a single&#xD;
      ascending dose and multiple ascending doses of FT-4202 in the context of Phase 1 studies in&#xD;
      healthy volunteers and sickle cell disease patients. The effects of food on the absorption of&#xD;
      FT-4202 will also be evaluated in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a first-in-human (FIH), Phase 1 study of FT-4202 that will characterize the safety,&#xD;
      PK and PD of FT-4202 after a single dose and after repeated dosing first in healthy adult&#xD;
      volunteers and then in adolescents or adults with sickle cell disease (SCD). Initially, a&#xD;
      dose range of FT-4202 in single ascending dose (SAD) escalation cohorts will be explored in&#xD;
      healthy subjects. Enrollment of healthy subjects into 2-week multiple ascending dose (MAD)&#xD;
      escalation cohorts will be initiated once the safety and PK from at least two SAD cohorts is&#xD;
      available to inform the doses for the 2-week MAD portion of the study. The MAD cohorts will&#xD;
      then run in parallel to the single dose cohorts. A single dose cohort of healthy subjects is&#xD;
      planned to understand food effects (FE) on the PK of FT-4202. After the SAD and FE studies in&#xD;
      healthy subjects are completed, the safety, PK, and PD of a single dose of FT-4202 that was&#xD;
      found to be safe in healthy subjects will then be evaluated in SCD subjects. Multiple dose&#xD;
      studies in SCD subjects will then be initiated upon completion of MAD studies in healthy&#xD;
      volunteers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 11, 2018</start_date>
  <completion_date type="Actual">December 17, 2021</completion_date>
  <primary_completion_date type="Actual">December 17, 2021</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Single ascending dose escalation and multiple ascending dose escalation study followed by an evaluation of food effects on absorption</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>randomized double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence, frequency, and severity of adverse events (AEs) per CTCAE v5.0 of a single ascending dose and multiple ascending doses of FT-4202 in adult healthy volunteers and SCD patients.</measure>
    <time_frame>Up to 3 weeks of monitoring</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to maximum observed plasma concentration (Tmax)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero until the 24-hour time point (AUC0-24)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal elimination half-life (t1/2)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent clearance (CL/F)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution (Vd/F)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal disposition rate constant (Lz)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal clearance (ClR)</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in the levels of 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) in the red blood cells (RBCs) of healthy volunteers and SCD patients after single and multiple doses of FT-4202.</measure>
    <time_frame>Up to 3 weeks of testing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Model-based estimate of change from baseline QT interval corrected using Fridericia's correction formula (QTcF) and 90% confidence interval at the estimated Cmax after a single dose of FT-4202 in healthy volunteers</measure>
    <time_frame>up to 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline heart rate after a single dose of FT-4202 in healthy volunteers</measure>
    <time_frame>up to 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline PR after a single dose of FT-4202 in healthy volunteers</measure>
    <time_frame>up to 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline QRS after a single dose of FT-4202 in healthy volunteers</measure>
    <time_frame>up to 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline T-wave morphology after a single dose of FT-4202 in healthy volunteers</measure>
    <time_frame>up to 7 days</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">130</enrollment>
  <condition>Healthy Volunteers</condition>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Single ascending dose cohorts in healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of FT-4202 or placebo. The first cohort will receive 200 mg of FT-4202 or placebo. Dose escalation will occur if FT-4202 or placebo is tolerated. The maximum dose of FT-4202 or placebo will be 1500 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple ascending dose cohorts in healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy volunteer subject cohorts randomized 9:3 to receive FT-4202 or placebo for 14 days continuous dosing. The first cohort will receive 100 mg of FT-4202 or placebo daily X 14 days. The maximum dose of FT-4202/placebo will be 600 mg FT-4202/placebo daily for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Food Effect Cohort in healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Health Volunteer subject cohort of 10 subjects who will receive a single dose of FT-4202 with food and without food. Dose will be administered per the protocol defined dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single ascending dose cohorts in SCD subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sickle cell disease subject cohort randomized 6:2 receiving a single dose of FT-4202 or placebo. The dose of FT-4202/placebo administered will be a dose that was found to be safe in healthy subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple ascending dose cohorts in SCD subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sickle cell disease subject cohorts randomized 9:3 to receive FT-4202 or placebo for 14 days continuous dosing. The dose of FT-4202/placebo administered will be a dose less than the maximum tolerable dose evaluated in MAD healthy volunteers.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12-week dosing cohort in SCD subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sickle cell disease subjects cohort to receive up to 84 consecutive daily doses of open-label FT-4202. The dose of FT-4202 administered will not exceed the highest dose evaluated in the MAD SCD subject cohorts</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FT-4202/Placebo</intervention_name>
    <description>Healthy volunteer subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies</description>
    <arm_group_label>Multiple ascending dose cohorts in healthy subjects</arm_group_label>
    <arm_group_label>Single ascending dose cohorts in healthy subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FT-4202</intervention_name>
    <description>Healthy volunteer subjects will receive FT-4202 with or without food and undergo pharmacokinetic studies</description>
    <arm_group_label>Food Effect Cohort in healthy subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FT-4202/Placebo</intervention_name>
    <description>SCD subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies</description>
    <arm_group_label>Multiple ascending dose cohorts in SCD subjects</arm_group_label>
    <arm_group_label>Single ascending dose cohorts in SCD subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FT-4202</intervention_name>
    <description>SCD subjects will receive FT-4202 and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies</description>
    <arm_group_label>12-week dosing cohort in SCD subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        SCD Key Inclusion Criteria:&#xD;
&#xD;
          -  Must be between 12 and 65 years of age&#xD;
&#xD;
          -  Previously diagnosed sickle cell disease (hemoglobin electrophoresis or genotype)&#xD;
&#xD;
          -  Must have a minimum body weight of 40 kg (88 lbs) at the Screening Visit&#xD;
&#xD;
          -  Must have the ability to understand and sign written informed consent (and assent&#xD;
             where applicable), which must be obtained prior to any study-related procedures being&#xD;
             completed&#xD;
&#xD;
          -  All male and female patients of child bearing potential must agree to use medically&#xD;
             accepted contraceptive regimen during study participation and for 90 days after last&#xD;
             study drug administration&#xD;
&#xD;
          -  Must be willing to abide by all study requirements and restrictions&#xD;
&#xD;
        SCD Key Exclusion Criteria:&#xD;
&#xD;
          -  Had more than 6 episodes of vaso-occlusive crisis (VOC) within the past 12 months that&#xD;
             required a hospital, emergency room, or clinic visit&#xD;
&#xD;
          -  Had a least one episode of acute chest syndrome in the last 6 months&#xD;
&#xD;
          -  Received any of the following approved therapies for use in SCD:&#xD;
&#xD;
               -  Hydroxurea (HU): excluded if started HU &lt; 90 days prior to Day 1 of study&#xD;
                  treatment&#xD;
&#xD;
               -  Adakveo®: excluded if received an infusion within 14 days prior to Day 1 of study&#xD;
                  treatment&#xD;
&#xD;
               -  Oxbryta®: excluded if received a dose within 7 days prior to start of Day 1 of&#xD;
                  study treatment&#xD;
&#xD;
          -  Received a red blood cell transfusion within 30 days of starting the study drug&#xD;
&#xD;
          -  Hemoglobin &lt; 7.0 g/dL or &gt; 10.5 g/dL&#xD;
&#xD;
          -  Unable to take and absorb oral medications&#xD;
&#xD;
        HEALTHY VOLUNTEER Inclusion Criteria: [NOTE: no longer recruiting subjects for this portion&#xD;
        of the study]&#xD;
&#xD;
          -  Subjects must be between 18 and 60 years of age&#xD;
&#xD;
          -  Subjects must have the ability to understand and sign written informed consent, which&#xD;
             must be obtained prior to any study-related procedures being completed&#xD;
&#xD;
          -  Subjects must be in general good health, based upon the results of medical history, a&#xD;
             physical examination, vital signs, laboratory profile, and a 12-lead ECG&#xD;
&#xD;
          -  All males and females of child bearing potential must agree to use medically accepted&#xD;
             contraceptive regimen during study participation and up to 90 days after&#xD;
&#xD;
          -  Subjects must be willing to abide by all study requirements and restrictions&#xD;
&#xD;
        HEALTHY VOLUNTEER Exclusion Criteria: [NOTE: no longer recruiting subjects for this portion&#xD;
        of the study]&#xD;
&#xD;
          -  Evidence of clinically significant medical condition or other condition that might&#xD;
             significantly interfere with the absorption, distribution, metabolism, or excretion of&#xD;
             study drug, or place the subject at an unacceptable risk as a participant in this&#xD;
             study&#xD;
&#xD;
          -  History of clinically significant cardiac diseases including condition disturbances&#xD;
&#xD;
          -  Abnormal hematologic, renal and liver function studies&#xD;
&#xD;
          -  History of drug or alcohol abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick Kelly, MD</last_name>
    <role>Study Director</role>
    <affiliation>Novo Nordisk A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Woodland International Research Group (SCD subjects only)</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Research, LLC (SCD subjects only)</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Partners (SCD subjects only)</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital Oakland (SCD subjects only)</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Pharma CR, LLC (SCD subjects only)</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33147</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta (SCD subjects only)</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University Medical Center (SCD subjects only)</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago (SCD subjects only)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland, Greenebaum Comprehensive Cancer Center (SCD subjects only)</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center (SCD subjects only)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute (SCD subjects only)</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center (SCD subjects only)</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center (SCD subjects only)</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medpace Clinical Pharmacology Unit (Healthy Volunteers only)</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center (SCD subjects only)</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Institute of Tulsa (SCD subjects only)</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital (SCD subjects only)</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston (SCD subjects only)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>July 13, 2022</last_update_submitted>
  <last_update_submitted_qc>July 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2022</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>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 17, 2023</submitted>
    <submission_canceled>May 17, 2023</submission_canceled>
    <submitted>June 20, 2023</submitted>
    <submission_canceled>July 12, 2023</submission_canceled>
    <submitted>August 8, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03815695
org study id: 4202-HVS-101
nct id: NCT03815695
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
FT-4202 is an oral small-molecule agonist of pyruvate kinase red blood cell isozyme (PKR)
      being developed for the treatment of hemolytic anemias. This initial study will characterize
      the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of a single
      ascending dose and multiple ascending doses of FT-4202 in the context of Phase 1 studies in
      healthy volunteers and sickle cell disease patients. The effects of food on the absorption of
      FT-4202 will also be evaluated in healthy volunteers.
This is a first-in-human (FIH), Phase 1 study of FT-4202 that will characterize the safety,
      PK and PD of FT-4202 after a single dose and after repeated dosing first in healthy adult
      volunteers and then in adolescents or adults with sickle cell disease (SCD). Initially, a
      dose range of FT-4202 in single ascending dose (SAD) escalation cohorts will be explored in
      healthy subjects. Enrollment of healthy subjects into 2-week multiple ascending dose (MAD)
      escalation cohorts will be initiated once the safety and PK from at least two SAD cohorts is
      available to inform the doses for the 2-week MAD portion of the study. The MAD cohorts will
      then run in parallel to the single dose cohorts. A single dose cohort of healthy subjects is
      planned to understand food effects (FE) on the PK of FT-4202. After the SAD and FE studies in
      healthy subjects are completed, the safety, PK, and PD of a single dose of FT-4202 that was
      found to be safe in healthy subjects will then be evaluated in SCD subjects. Multiple dose
      studies in SCD subjects will then be initiated upon completion of MAD studies in healthy
      volunteers.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Single ascending dose escalation and multiple ascending dose escalation study followed by an evaluation of food effects on absorption
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: randomized double blind
measure: Incidence, frequency, and severity of adverse events (AEs) per CTCAE v5.0 of a single ascending dose and multiple ascending doses of FT-4202 in adult healthy volunteers and SCD patients.
time frame: Up to 3 weeks of monitoring
measure: Maximum observed plasma concentration (Cmax)
time frame: Up to 3 weeks of testing
measure: Time to maximum observed plasma concentration (Tmax)
time frame: Up to 3 weeks of testing
measure: Area under the plasma concentration-time curve from time zero until the 24-hour time point (AUC0-24)
time frame: Up to 3 weeks of testing
measure: Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last)
time frame: Up to 3 weeks of testing
measure: Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf)
time frame: Up to 3 weeks of testing
measure: Terminal elimination half-life (t1/2)
time frame: Up to 3 weeks of testing
measure: Apparent clearance (CL/F)
time frame: Up to 3 weeks of testing
measure: Apparent volume of distribution (Vd/F)
time frame: Up to 3 weeks of testing
measure: Terminal disposition rate constant (Lz)
time frame: Up to 3 weeks of testing
measure: Renal clearance (ClR)
time frame: Up to 3 weeks of testing
measure: Change from baseline in the levels of 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) in the red blood cells (RBCs) of healthy volunteers and SCD patients after single and multiple doses of FT-4202.
time frame: Up to 3 weeks of testing
measure: Model-based estimate of change from baseline QT interval corrected using Fridericia's correction formula (QTcF) and 90% confidence interval at the estimated Cmax after a single dose of FT-4202 in healthy volunteers
time frame: up to 7 days
measure: Change from baseline heart rate after a single dose of FT-4202 in healthy volunteers
time frame: up to 7 days
measure: Change from baseline PR after a single dose of FT-4202 in healthy volunteers
time frame: up to 7 days
measure: Change from baseline QRS after a single dose of FT-4202 in healthy volunteers
time frame: up to 7 days
measure: Change from baseline T-wave morphology after a single dose of FT-4202 in healthy volunteers
time frame: up to 7 days
arm group label: Single ascending dose cohorts in healthy subjects
arm group type: Experimental
description: Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of FT-4202 or placebo. The first cohort will receive 200 mg of FT-4202 or placebo. Dose escalation will occur if FT-4202 or placebo is tolerated. The maximum dose of FT-4202 or placebo will be 1500 mg.
arm group label: Multiple ascending dose cohorts in healthy subjects
arm group type: Experimental
description: Healthy volunteer subject cohorts randomized 9:3 to receive FT-4202 or placebo for 14 days continuous dosing. The first cohort will receive 100 mg of FT-4202 or placebo daily X 14 days. The maximum dose of FT-4202/placebo will be 600 mg FT-4202/placebo daily for 14 days.
arm group label: Food Effect Cohort in healthy subjects
arm group type: Experimental
description: Health Volunteer subject cohort of 10 subjects who will receive a single dose of FT-4202 with food and without food. Dose will be administered per the protocol defined dose.
arm group label: Single ascending dose cohorts in SCD subjects
arm group type: Experimental
description: Sickle cell disease subject cohort randomized 6:2 receiving a single dose of FT-4202 or placebo. The dose of FT-4202/placebo administered will be a dose that was found to be safe in healthy subjects.
arm group label: Multiple ascending dose cohorts in SCD subjects
arm group type: Experimental
description: Sickle cell disease subject cohorts randomized 9:3 to receive FT-4202 or placebo for 14 days continuous dosing. The dose of FT-4202/placebo administered will be a dose less than the maximum tolerable dose evaluated in MAD healthy volunteers.
arm group label: 12-week dosing cohort in SCD subjects
arm group type: Experimental
description: Sickle cell disease subjects cohort to receive up to 84 consecutive daily doses of open-label FT-4202. The dose of FT-4202 administered will not exceed the highest dose evaluated in the MAD SCD subject cohorts
intervention type: Drug
intervention name: FT-4202/Placebo
description: Healthy volunteer subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
arm group label: Multiple ascending dose cohorts in healthy subjects
arm group label: Single ascending dose cohorts in healthy subjects
intervention type: Drug
intervention name: FT-4202
description: Healthy volunteer subjects will receive FT-4202 with or without food and undergo pharmacokinetic studies
arm group label: Food Effect Cohort in healthy subjects
intervention type: Drug
intervention name: FT-4202/Placebo
description: SCD subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
arm group label: Multiple ascending dose cohorts in SCD subjects
arm group label: Single ascending dose cohorts in SCD subjects
intervention type: Drug
intervention name: FT-4202
description: SCD subjects will receive FT-4202 and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
arm group label: 12-week dosing cohort in SCD subjects
criteria: 
gender: All
minimum age: 12 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Patrick Kelly, MD
role: Study Director
affiliation: Novo Nordisk A/S
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country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: No
submitted: May 17, 2023
submission canceled: May 17, 2023
submitted: June 20, 2023
submission canceled: July 12, 2023
submitted: August 8, 2023