<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/NCT03828084</url>
  </required_header>
  <id_info>
    <org_study_id>EPI-01-CP.001</org_study_id>
    <nct_id>NCT03828084</nct_id>
  </id_info>
  <brief_title>Randomized, Single-dose, Crossover Study of 4 Decitabine and Tetrahydrouridine (EPI01) Formulations in Healthy Subjects</brief_title>
  <acronym>EPI01</acronym>
  <official_title>An Open-Label, Randomized, Single-Dose, Four-Way Crossover, Bioavailability Study of Three Formulations of Decitabine/Tetrahydrouridine (THU) Combination Modified Release Capsules (5 mg/250 mg) in Healthy and Fasting Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EpiDestiny, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>EpiDestiny, Inc.</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>
      To study the pharmacokinetic profiles of decitabine and tetrahydrouridine (THU) from 3&#xD;
      modified release formulations in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, randomized, single-dose per period, four-period, crossover study to&#xD;
      evaluate relative bioavailability of decitabine in three newly formulated THU and decitabine&#xD;
      combination capsules in comparison to 3 capsules of THU followed 1 hour later by 3 capsules&#xD;
      of decitabine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 3, 2019</start_date>
  <completion_date type="Actual">May 3, 2019</completion_date>
  <primary_completion_date type="Actual">May 2, 2019</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Four-way crossover, single dose with a 7 days washout period in between periods</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of Decitabine</measure>
    <time_frame>24 hours</time_frame>
    <description>Area under the concentration-time curve (AUC) from time of dosing to the last quantifiable concentration of Decitabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decitabine plasma concentration</measure>
    <time_frame>24 hours</time_frame>
    <description>Maximum concentration (Cmax) of Decitabine in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of Tetrahydrouridine</measure>
    <time_frame>24 hours</time_frame>
    <description>Area under the concentration-time curve (AUC) from time of dosing to the last quantifiable concentration of THU</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of Decitabine and Tetrahydrouridine</measure>
    <time_frame>24 hours</time_frame>
    <description>Safety of single dose as measured by adverse event reporting</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Formulation A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 test capsules of combination decitabine/THU (5 mg/250 mg per capsule; Formulation A) given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Formulation B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 test capsules of combination decitabine/THU (5 mg/250 mg per capsule; Formulation B) given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Formulation C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 test capsules of combination decitabine/THU (5 mg/250 mg per capsule; Formulation C) given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference Formulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3 capsules of THU (250 mg per capsule) given as a single oral dose with approximately 240 mL of ambient temperature water, followed by a single oral dose of 3 capsules of decitabine (5 mg per capsule) given 1 hour later with approximately 240 mL of ambient temperature water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decitabine</intervention_name>
    <description>Combination drugs containing decitabine and tetrahydrouridine</description>
    <arm_group_label>Formulation A</arm_group_label>
    <arm_group_label>Formulation B</arm_group_label>
    <arm_group_label>Formulation C</arm_group_label>
    <arm_group_label>Reference Formulation</arm_group_label>
    <other_name>Tetrahydrouridine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must understand and voluntarily sign a written ICF prior to any study related&#xD;
             procedures being performed and be able to adhere to restrictions and examination&#xD;
             schedules.&#xD;
&#xD;
          -  Must be able to communicate with the investigator, and to understand and comply with&#xD;
             the requirements of the study.&#xD;
&#xD;
          -  Healthy male volunteers from any race between 18 to 50 years of age (inclusive), and&#xD;
             in good health as determined by past medical history, physical examination, vital&#xD;
             signs, ECG, and laboratory tests at screening.&#xD;
&#xD;
          -  Must have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and a weight&#xD;
             between 60 and 100 kg (132 to 220 lb), inclusive, at screening.&#xD;
&#xD;
          -  Subject's clinical laboratory test results have no clinically significant findings, in&#xD;
             the opinion of the Investigator.&#xD;
&#xD;
          -  Vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in&#xD;
             the supine position after the subject has rested for at least 5 minutes. At screening,&#xD;
             the potential subject must be afebrile, with a systolic blood pressure between 90 and&#xD;
             140 mmHg (inclusive), diastolic blood pressure between 60 and 90 mmHg (inclusive), and&#xD;
             pulse rate between 50 and 100 bpm (inclusive). Vital signs criteria at each check-in&#xD;
             and the pre-dose measurements will be at the Investigator's discretion.&#xD;
&#xD;
          -  Subjects must be free of any clinically significant disease that would interfere with&#xD;
             the study evaluations.&#xD;
&#xD;
          -  Subjects (including those who have had a documented vasectomy) must be using a&#xD;
             double-barrier local contraception (i.e., spermicidal gel plus condom) when engaging&#xD;
             in sexual activity with women of childbearing potential while on study medication and&#xD;
             for 28 days after the last dose of study medication.&#xD;
&#xD;
          -  Subjects must refrain from sperm donations while on study drug, for the entire&#xD;
             duration of the study, and for 28 days after the last dose of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of clinically significant cardiovascular, pulmonary, hepatic,&#xD;
             renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,&#xD;
             neurologic, oncologic, or psychiatric disease or any other condition, including the&#xD;
             presence of laboratory abnormalities, that, in the opinion of the Investigator, would&#xD;
             jeopardize the safety of the subject or the validity of the study results.&#xD;
&#xD;
          -  Any serious medical condition, clinically significant laboratory abnormality, or&#xD;
             psychiatric illness that would prevent the subject from signing the ICF.&#xD;
&#xD;
          -  Recent history within 3 years of any clinically significant neurological,&#xD;
             gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic,&#xD;
             endocrine, hematological or other major disorders.&#xD;
&#xD;
          -  Used any prescribed systemic or topical medication within 30 days of the first dose&#xD;
             administration.&#xD;
&#xD;
          -  Used any non-prescribed systemic (including herbal medicines, e.g. St. John's Wort) or&#xD;
             topical medication within 7 days of the first dose administration (with the exception&#xD;
             of vitamin/mineral supplements)&#xD;
&#xD;
          -  Subjects who have any surgical or medical conditions possibly affecting drug&#xD;
             absorption, distribution, metabolism and excretion (ADME).&#xD;
&#xD;
          -  Exposed to an investigational drug (new chemical entity) within 90 days preceding the&#xD;
             first dose administration or currently enrolled in any investigational trials.&#xD;
&#xD;
          -  Donated blood or plasma within 8 weeks preceding the first dose administration.&#xD;
&#xD;
          -  History of multiple drug allergies.&#xD;
&#xD;
          -  Any clinically significant allergic disease (excluding nonactive hay fever).&#xD;
&#xD;
          -  History of drug abuse of at least 2 years prior to dosing, or positive drug screening&#xD;
             test due to illicit drugs.&#xD;
&#xD;
          -  History of alcohol abuse of at least 2 years prior to dosing, or positive alcohol&#xD;
             screen.&#xD;
&#xD;
          -  Smokers or users of other tobacco products (e.g., chewing tobacco, or those using&#xD;
             nicotine-containing products (i.e., patches, gum) in the 3 months prior to screening,&#xD;
             or positive urine cotinine test.&#xD;
&#xD;
          -  Known to have serum hepatitis or known to be a carrier of the hepatitis B surface&#xD;
             antigen (HBsAg) or hepatitis C antibody, or tests positive for HIV (human&#xD;
             immunodeficiency virus) antibodies at screening.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cynthia A Zamora, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Worldwide Clinical Trials Early Phase Services, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Worldwide Clinical Trial</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.worldwide.com/participate-in-a-study/</url>
    <description>To participate in a Worldwide clinical trial</description>
  </link>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>May 7, 2019</last_update_submitted>
  <last_update_submitted_qc>May 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 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>Decitabine</mesh_term>
    <mesh_term>Tetrahydrouridine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT03828084
org study id: EPI-01-CP.001
nct id: NCT03828084
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To study the pharmacokinetic profiles of decitabine and tetrahydrouridine (THU) from 3
      modified release formulations in healthy subjects.
This is an open-label, randomized, single-dose per period, four-period, crossover study to
      evaluate relative bioavailability of decitabine in three newly formulated THU and decitabine
      combination capsules in comparison to 3 capsules of THU followed 1 hour later by 3 capsules
      of decitabine.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Four-way crossover, single dose with a 7 days washout period in between periods
primary purpose: Other
masking: None (Open Label)
measure: Pharmacokinetics of Decitabine
time frame: 24 hours
description: Area under the concentration-time curve (AUC) from time of dosing to the last quantifiable concentration of Decitabine
measure: Decitabine plasma concentration
time frame: 24 hours
description: Maximum concentration (Cmax) of Decitabine in plasma
measure: Pharmacokinetics of Tetrahydrouridine
time frame: 24 hours
description: Area under the concentration-time curve (AUC) from time of dosing to the last quantifiable concentration of THU
measure: Safety of Decitabine and Tetrahydrouridine
time frame: 24 hours
description: Safety of single dose as measured by adverse event reporting
arm group label: Formulation A
arm group type: Experimental
description: 3 test capsules of combination decitabine/THU (5 mg/250 mg per capsule; Formulation A) given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.
arm group label: Formulation B
arm group type: Experimental
description: 3 test capsules of combination decitabine/THU (5 mg/250 mg per capsule; Formulation B) given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.
arm group label: Formulation C
arm group type: Experimental
description: 3 test capsules of combination decitabine/THU (5 mg/250 mg per capsule; Formulation C) given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.
arm group label: Reference Formulation
arm group type: Active Comparator
description: 3 capsules of THU (250 mg per capsule) given as a single oral dose with approximately 240 mL of ambient temperature water, followed by a single oral dose of 3 capsules of decitabine (5 mg per capsule) given 1 hour later with approximately 240 mL of ambient temperature water.
intervention type: Drug
intervention name: Decitabine
description: Combination drugs containing decitabine and tetrahydrouridine
arm group label: Formulation A
arm group label: Formulation B
arm group label: Formulation C
arm group label: Reference Formulation
other name: Tetrahydrouridine
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cynthia A Zamora, MD
role: Principal Investigator
affiliation: Worldwide Clinical Trials Early Phase Services, LLC
facility: 
country: United States
url: https://www.worldwide.com/participate-in-a-study/
description: To participate in a Worldwide clinical trial
responsible party type: Sponsor
mesh term: Decitabine
mesh term: Tetrahydrouridine
sharing ipd: Undecided
ipd description: Undecided