<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/NCT03795519</url>
  </required_header>
  <id_info>
    <org_study_id>OLI-103</org_study_id>
    <nct_id>NCT03795519</nct_id>
  </id_info>
  <brief_title>A Trial to Study the Absorption, Metabolism, and Excretion of [14C]-Olinciguat in Healthy Male Volunteers</brief_title>
  <official_title>A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Olinciguat ([14C]-IW-1701) 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective is to characterize the pharmacokinetics (PK) of olinciguat and total&#xD;
      radioactivity and to assess the elimination of total radioactivity from a single oral dose of&#xD;
      [14C]-olinciguat.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OLI-103 is a Phase 1 open-label, nonrandomized, single-dose study in up to 8 subjects that&#xD;
      will be conducted at a single center in the US. Safety assessments will be performed&#xD;
      throughout the clinic period and multiple PK samples will be collected. Subjects will be&#xD;
      confined to the clinical research center for at least 8 days.&#xD;
&#xD;
      The purpose of the study is to determine the absorption, metabolism, and excretion of&#xD;
      [14C]-olinciguat and to characterize and determine, where possible, the metabolites present&#xD;
      in plasma, urine, and feces after a single oral dose. The study will help identify and&#xD;
      characterize olinciguat metabolites, evaluate the likelihood of effects of liver or kidney&#xD;
      impairment on the disposition of olinciguat, and assess the likelihood of drug-drug&#xD;
      interactions with olinciguat.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Actual">February 27, 2019</completion_date>
  <primary_completion_date type="Actual">February 27, 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 olinciguat 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 olinciguat 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 olinciguat 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 olinciguat 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 olinciguat 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 olinciguat (CL/F)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution of olinciguat (Vz/F)</measure>
    <time_frame>up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-inf of plasma olinciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Olinciguat/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]-olinciguat</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C]-olinciguat</intervention_name>
    <description>oral capsule</description>
    <arm_group_label>Healthy Male Volunteers</arm_group_label>
    <other_name>14C-IW-1701</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>Bina Tejura, 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>April 2019</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>April 1, 2019</last_update_submitted>
  <last_update_submitted_qc>April 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT03795519
org study id: OLI-103
nct id: NCT03795519
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective is to characterize the pharmacokinetics (PK) of olinciguat and total
      radioactivity and to assess the elimination of total radioactivity from a single oral dose of
      [14C]-olinciguat.
OLI-103 is a Phase 1 open-label, nonrandomized, single-dose study in up to 8 subjects that
      will be conducted at a single center in the US. Safety assessments will be performed
      throughout the clinic period and multiple PK samples will be collected. Subjects will be
      confined to the clinical research center for at least 8 days.

      The purpose of the study is to determine the absorption, metabolism, and excretion of
      [14C]-olinciguat and to characterize and determine, where possible, the metabolites present
      in plasma, urine, and feces after a single oral dose. The study will help identify and
      characterize olinciguat metabolites, evaluate the likelihood of effects of liver or kidney
      impairment on the disposition of olinciguat, and assess the likelihood of drug-drug
      interactions with olinciguat.
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 olinciguat 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 olinciguat 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 olinciguat 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 olinciguat 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 olinciguat 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 olinciguat (CL/F)
time frame: up to Day 15
measure: Apparent volume of distribution of olinciguat (Vz/F)
time frame: up to Day 15
measure: AUC0-inf of plasma olinciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Olinciguat/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]-olinciguat
intervention type: Drug
intervention name: [14C]-olinciguat
description: oral capsule
arm group label: Healthy Male Volunteers
other name: 14C-IW-1701
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bina Tejura, MD
role: Study Director
affiliation: Ironwood Pharmaceuticals, Inc.
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No