<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/NCT03818295</url>
  </required_header>
  <id_info>
    <org_study_id>PRL-105</org_study_id>
    <nct_id>NCT03818295</nct_id>
  </id_info>
  <brief_title>A Trial to Study the Absorption, Metabolism, and Excretion of [14C]-Praliciguat in Healthy Male Volunteers</brief_title>
  <official_title>A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Praliciguat ([14C]-IW-1973) Following a Single Oral Dose in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cyclerion Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cyclerion Therapeutics</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective is to characterize the pharmacokinetics (PK) of praliciguat and total&#xD;
      radioactivity and to assess the elimination of total radioactivity from a single oral dose of&#xD;
      [14C]-praliciguat.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Actual">April 24, 2019</completion_date>
  <primary_completion_date type="Actual">April 24, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Amount of total radioactivity excreted in urine (Aeu) and feces (Aef)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Aeu and cumulative Aef</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of total radioactivity excreted in urine (feu) and feces (fef)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative feu and cumulative fef</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of total radioactivity in total excreta (feces + urine)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of praliciguat in plasma</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-inf of total radioactivity in plasma and whole blood</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC from time zero to the last quantifiable concentration (AUC0-last) of praliciguat in plasma</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-last of total radioactivity in plasma and whole blood</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed concentration (Cmax) of praliciguat in plasma</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of total radioactivity in plasma and whole blood</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of Cmax (Tmax) of praliciguat in plasma</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax of total radioactivity in plasma and whole blood</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent terminal elimination half-life (t1/2) of praliciguat in plasma</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2 total radioactivity in plasma and whole blood</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent total clearance of praliciguat (CL/F)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution of praliciguat (Vz/F)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-inf of plasma praliciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Praliciguat/Plasma Total Radioactivity)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-inf of whole blood total radioactivity to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Blood Total Radioactivity/Plasma Total Radioactivity)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Levels of metabolite radioactivity excreted in urine and feces</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf of metabolite radioactivity levels in plasma</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf of plasma metabolite radioactivity levels relative to AUC0-inf of plasma total radioactivity (Plasma AUC0-inf Ratio of Metabolite Radioactivity/Total Radioactivity)</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chromatographic retention time of metabolites</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular ion mass of metabolites</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristic mass spectrometry fragmentation ions of metabolites</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chemical structures (graphical representations showing atom connectivity) proposed for plasma, urine, and feces metabolites</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number(s) of participants with ≥1 treatment-emergent serious adverse event (SAE)</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number(s) of participants with ≥1 adverse event (AE) leading to study drug discontinuation</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number(s) of participants with ≥1 Grade ≥3 AE (per CTCAE v. 5.0)</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number(s) of participants with ≥1 clinically significant abnormal physical examination finding</measure>
    <time_frame>up to Day 15</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Healthy Male Volunteers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral dose of [14C]-praliciguat</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C]-praliciguat</intervention_name>
    <description>10 mg praliciguat containing approximately 500 μCi of [14C]-praliciguat</description>
    <arm_group_label>Healthy Male Volunteers</arm_group_label>
    <other_name>[14C]-IW-1973</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males of any race, between 18 and 55 years of age, inclusive&#xD;
&#xD;
          -  Body mass index between 18 and 32 kg/m2, inclusive&#xD;
&#xD;
          -  Subject is in good health and has no clinically significant findings on physical&#xD;
             examination&#xD;
&#xD;
          -  Men must agree to use protocol-specified contraception and also to not donate sperm&#xD;
             throughout the study and for at least 90 days after the final dose of study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any active or unstable clinically significant medical condition&#xD;
&#xD;
          -  Use of any prescribed or non-prescribed medication&#xD;
&#xD;
        Additional inclusion/exclusion criteria may apply per protocol&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Hanrahan, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ironwood Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Clinical Research Unit Inc.</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>June 18, 2019</last_update_submitted>
  <last_update_submitted_qc>June 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Praliciguat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03818295
org study id: PRL-105
nct id: NCT03818295
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary objective is to characterize the pharmacokinetics (PK) of praliciguat and total
      radioactivity and to assess the elimination of total radioactivity from a single oral dose of
      [14C]-praliciguat.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Amount of total radioactivity excreted in urine (Aeu) and feces (Aef)
time frame: up to Day 15
measure: Cumulative Aeu and cumulative Aef
time frame: up to Day 15
measure: Percentage of total radioactivity excreted in urine (feu) and feces (fef)
time frame: up to Day 15
measure: Cumulative feu and cumulative fef
time frame: up to Day 15
measure: Percentage of total radioactivity in total excreta (feces + urine)
time frame: up to Day 15
measure: Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of praliciguat in plasma
time frame: up to Day 15
measure: AUC0-inf of total radioactivity in plasma and whole blood
time frame: up to Day 15
measure: AUC from time zero to the last quantifiable concentration (AUC0-last) of praliciguat in plasma
time frame: up to Day 15
measure: AUC0-last of total radioactivity in plasma and whole blood
time frame: up to Day 15
measure: Maximum observed concentration (Cmax) of praliciguat in plasma
time frame: up to Day 15
measure: Cmax of total radioactivity in plasma and whole blood
time frame: up to Day 15
measure: Time of Cmax (Tmax) of praliciguat in plasma
time frame: up to Day 15
measure: Tmax of total radioactivity in plasma and whole blood
time frame: up to Day 15
measure: Apparent terminal elimination half-life (t1/2) of praliciguat in plasma
time frame: up to Day 15
measure: t1/2 total radioactivity in plasma and whole blood
time frame: up to Day 15
measure: Apparent total clearance of praliciguat (CL/F)
time frame: up to Day 15
measure: Apparent volume of distribution of praliciguat (Vz/F)
time frame: up to Day 15
measure: AUC0-inf of plasma praliciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Praliciguat/Plasma Total Radioactivity)
time frame: up to Day 15
measure: AUC0-inf of whole blood total radioactivity to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Blood Total Radioactivity/Plasma Total Radioactivity)
time frame: up to Day 15
measure: Levels of metabolite radioactivity excreted in urine and feces
time frame: up to Day 15
measure: AUC0-inf of metabolite radioactivity levels in plasma
time frame: up to Day 15
measure: AUC0-inf of plasma metabolite radioactivity levels relative to AUC0-inf of plasma total radioactivity (Plasma AUC0-inf Ratio of Metabolite Radioactivity/Total Radioactivity)
time frame: up to Day 15
measure: Chromatographic retention time of metabolites
time frame: up to Day 15
measure: Molecular ion mass of metabolites
time frame: up to Day 15
measure: Characteristic mass spectrometry fragmentation ions of metabolites
time frame: up to Day 15
measure: Chemical structures (graphical representations showing atom connectivity) proposed for plasma, urine, and feces metabolites
time frame: up to Day 15
measure: Number(s) of participants with ≥1 treatment-emergent serious adverse event (SAE)
time frame: up to Day 15
measure: Number(s) of participants with ≥1 adverse event (AE) leading to study drug discontinuation
time frame: up to Day 15
measure: Number(s) of participants with ≥1 Grade ≥3 AE (per CTCAE v. 5.0)
time frame: up to Day 15
measure: Number(s) of participants with ≥1 clinically significant abnormal physical examination finding
time frame: up to Day 15
arm group label: Healthy Male Volunteers
arm group type: Experimental
description: Single oral dose of [14C]-praliciguat
intervention type: Drug
intervention name: [14C]-praliciguat
description: 10 mg praliciguat containing approximately 500 μCi of [14C]-praliciguat
arm group label: Healthy Male Volunteers
other name: [14C]-IW-1973
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John Hanrahan, MD
role: Study Director
affiliation: Ironwood Pharmaceuticals, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Praliciguat
sharing ipd: No