<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/NCT03294707</url>
  </required_header>
  <id_info>
    <org_study_id>AG10-001</org_study_id>
    <nct_id>NCT03294707</nct_id>
  </id_info>
  <brief_title>Single and Multiple Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of AG10</brief_title>
  <official_title>A Phase 1 Randomized, Placebo-controlled, Single and Multiple Ascending Dose Study of the Tolerability, Pharmacokinetics and Pharmacodynamics of AG10 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eidos Therapeutics, a BridgeBio company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celerion</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Eidos Therapeutics, a BridgeBio company</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>
      This is a single center, prospective, randomized, placebo-controlled study of AG10 in healthy&#xD;
      adult subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 48 healthy volunteers will be given a single dose of AG10 or placebo and be monitored&#xD;
      for safety and tolerability over a 5-day period. Up to 48 healthy volunteers will be given&#xD;
      multiple doses of AG10 or placebo and be monitored for safety and tolerability over a 15-day&#xD;
      period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Actual">May 18, 2018</completion_date>
  <primary_completion_date type="Actual">February 5, 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Subjects will be randomized with an overall ratio of 3:1 to AG10: placebo within each cohort</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safety &amp; tolerability: individual and summary blood pressures, heart rate, ECG and lab data presented in tabular form with descriptive statistics. Adverse events will be tabulated and summarized by Part A (SAD) vs. B (MAD), and treatment.</measure>
    <time_frame>30 days</time_frame>
    <description>To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: T1/2</measure>
    <time_frame>30 days</time_frame>
    <description>Plasma half-life (t1/2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: Tmax</measure>
    <time_frame>30 days</time_frame>
    <description>Time to maximum concentration (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: Cmax</measure>
    <time_frame>30 days</time_frame>
    <description>Maximum concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: Cmin</measure>
    <time_frame>30 days</time_frame>
    <description>Cmin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: AUC</measure>
    <time_frame>30 days</time_frame>
    <description>Area under the plasma concentration-time curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: Clearance</measure>
    <time_frame>30 days</time_frame>
    <description>Apparent clearance (CL/F)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessments: volume of distribution</measure>
    <time_frame>30 days</time_frame>
    <description>Apparent volume of distribution (Vss/F)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessments: Assessments of TTR stabilization will be listed and summarized by part, treatment, and time point using appropriate descriptive statistics.</measure>
    <time_frame>30 days</time_frame>
    <description>AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays, including Fluorescent Polarization Exclusion Assay (FPE) and Immunoblotting (Western Blot) and quantitation of prealbumin (TTR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessments: Western blot</measure>
    <time_frame>30 days</time_frame>
    <description>AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessments: prealbumin</measure>
    <time_frame>30 days</time_frame>
    <description>AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food effect: AUC</measure>
    <time_frame>30 days</time_frame>
    <description>To evaluate the effect of food on the PK of AG10. The log transformed values of total AUC will be analyzed using a linear mixed effect model with formulation, period, sequence, and carryover as fixed effects and subject as a random effect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food effect: Cmax</measure>
    <time_frame>30 days</time_frame>
    <description>To evaluate the effect of food on the PK of AG10. The log transformed values of Cmax will be analyzed using a linear mixed effect model with formulation, period, sequence, and carryover as fixed effects and subject as a random effect.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Amyloid Cardiomyopathy, Transthyretin-Related</condition>
  <arm_group>
    <arm_group_label>AG10 single oral dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AG10 oral tablet, administered by mouth, once</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo single oral dose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Oral Tablet, administered by mouth, once</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG10 oral tablet</intervention_name>
    <description>Active single ascending dose</description>
    <arm_group_label>AG10 single oral dose</arm_group_label>
    <other_name>Eidos Therapeutics AG10</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Placebo single dose</description>
    <arm_group_label>Placebo single oral dose</arm_group_label>
    <other_name>Matching placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Weight between &gt;50 kg and ≤110 kg;&#xD;
&#xD;
          -  BMI of 18 to 32 kg/m2;&#xD;
&#xD;
          -  Subjects who are healthy as determined by medical history, physical examination, 12&#xD;
             lead ECG and standard laboratory tests;&#xD;
&#xD;
          -  Subjects who are negative for drugs of abuse and alcohol tests;&#xD;
&#xD;
          -  Subjects who are non-smokers;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have used prescription drugs within 4 weeks of first dosing;&#xD;
&#xD;
          -  Subjects who have a prior cholecystectomy;&#xD;
&#xD;
          -  Subjects who have used any over-the-counter medications within 7 days prior to Day -1;&#xD;
&#xD;
          -  Subjects who have a clinically relevant history or presence of respiratory,&#xD;
             gastrointestinal, renal, hepatic, hematological, lymphatic, neurological,&#xD;
             cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological,&#xD;
             dermatological, or connective tissue diseases or disorders;&#xD;
&#xD;
          -  Subjects who have an abnormal screening ECG;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Terry O'Reilly, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Celerion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>May 21, 2018</last_update_submitted>
  <last_update_submitted_qc>May 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2018</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>Cardiomyopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coal Tar</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/NCT03294707
org study id: AG10-001
nct id: NCT03294707
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single center, prospective, randomized, placebo-controlled study of AG10 in healthy
      adult subjects
Up to 48 healthy volunteers will be given a single dose of AG10 or placebo and be monitored
      for safety and tolerability over a 5-day period. Up to 48 healthy volunteers will be given
      multiple doses of AG10 or placebo and be monitored for safety and tolerability over a 15-day
      period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Subjects will be randomized with an overall ratio of 3:1 to AG10: placebo within each cohort
measure: Safety & tolerability: individual and summary blood pressures, heart rate, ECG and lab data presented in tabular form with descriptive statistics. Adverse events will be tabulated and summarized by Part A (SAD) vs. B (MAD), and treatment.
time frame: 30 days
description: To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects
measure: Pharmacokinetic Assessments: T1/2
time frame: 30 days
description: Plasma half-life (t1/2)
measure: Pharmacokinetic Assessments: Tmax
time frame: 30 days
description: Time to maximum concentration (Tmax)
measure: Pharmacokinetic Assessments: Cmax
time frame: 30 days
description: Maximum concentration (Cmax)
measure: Pharmacokinetic Assessments: Cmin
time frame: 30 days
description: Cmin
measure: Pharmacokinetic Assessments: AUC
time frame: 30 days
description: Area under the plasma concentration-time curve (AUC)
measure: Pharmacokinetic Assessments: Clearance
time frame: 30 days
description: Apparent clearance (CL/F)
measure: Pharmacokinetic Assessments: volume of distribution
time frame: 30 days
description: Apparent volume of distribution (Vss/F)
measure: Pharmacodynamic Assessments: Assessments of TTR stabilization will be listed and summarized by part, treatment, and time point using appropriate descriptive statistics.
time frame: 30 days
description: AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays, including Fluorescent Polarization Exclusion Assay (FPE) and Immunoblotting (Western Blot) and quantitation of prealbumin (TTR).
measure: Pharmacodynamic Assessments: Western blot
time frame: 30 days
description: AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)
measure: Pharmacodynamic Assessments: prealbumin
time frame: 30 days
description: AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).
measure: Food effect: AUC
time frame: 30 days
description: To evaluate the effect of food on the PK of AG10. The log transformed values of total AUC will be analyzed using a linear mixed effect model with formulation, period, sequence, and carryover as fixed effects and subject as a random effect.
measure: Food effect: Cmax
time frame: 30 days
description: To evaluate the effect of food on the PK of AG10. The log transformed values of Cmax will be analyzed using a linear mixed effect model with formulation, period, sequence, and carryover as fixed effects and subject as a random effect.
arm group label: AG10 single oral dose
arm group type: Experimental
description: AG10 oral tablet, administered by mouth, once
arm group label: Placebo single oral dose
arm group type: Placebo Comparator
description: Placebo Oral Tablet, administered by mouth, once
intervention type: Drug
intervention name: AG10 oral tablet
description: Active single ascending dose
arm group label: AG10 single oral dose
other name: Eidos Therapeutics AG10
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Placebo single dose
arm group label: Placebo single oral dose
other name: Matching placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Terry O'Reilly, M.D.
role: Principal Investigator
affiliation: Celerion
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Coal Tar
sharing ipd: No