<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/NCT02194491</url>
  </required_header>
  <id_info>
    <org_study_id>3662-CL-0011</org_study_id>
    <nct_id>NCT02194491</nct_id>
  </id_info>
  <brief_title>A Positron Emission Tomography Occupancy Study Using Ligand [11C]AS2471907 and Following Oral Dosing of ASP3662</brief_title>
  <official_title>A Phase 1 11β-Hydroxysteroid Dehydrogenase 1 Enzyme Occupancy Study Using a Positron Emission Tomography Ligand [11C]AS2471907- ([11C]MOZAT) and Following Single Oral Dose Administration of ASP3662 in Healthy Male Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astellas Pharma Global Development, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Astellas Pharma Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate a novel PET tracer ([11C]AS2471907), and to use&#xD;
      [11C]AS2471907 to assess the level and time-course of enzyme occupancy in the human brain&#xD;
      prior to and following single oral dose administration of ASP3662.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a two-part study where Part 1 will assess the test/retest variability of the ligand&#xD;
      ([11C]AS2471907). Part 2 will assess the level and time-course of enzyme occupancy following&#xD;
      ASP3662 dosing. Subjects will be confined to the clinic for up to 2 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Positron Emission Tomography measure: volume of distribution</measure>
    <time_frame>Day 1 and 2 (Part 1 and Part 2)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Positron Emission Tomography measure: brain time-activity curves</measure>
    <time_frame>Day 1 and 2 (Part 1 and Part 2)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Positron Emission Tomography measure: enzyme occupancy</measure>
    <time_frame>Day 1 and 2 (Part 1 and Part 2)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Positron Emission Tomography measure: binding potentials</measure>
    <time_frame>Day 1 and 2 (Part 1 and Part 2)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): AUClast (Part 2 only)</measure>
    <time_frame>Day 1 and 2</time_frame>
    <description>Area under the plasma concentration - time curve from time zero to time of last measurable concentration (AUClast)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): Cmax (Part 2 only)</measure>
    <time_frame>Day 1 and 2</time_frame>
    <description>Maximum concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): tmax (Part 2 only)</measure>
    <time_frame>Day 1 and 2</time_frame>
    <description>Time to attain Cmax (tmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety as assessed by laboratory tests, 12-lead electrocardiograms, vital signs, adverse events, physical exams, neurological exams and Columbia Suicide Severity Rating Scale</measure>
    <time_frame>up to 9 days (Part 1 and Part 2)</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Pharmacokinetics of ASP3662</condition>
  <condition>Displacement of Radiotracer</condition>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>[11C]AS2471907 administration (Part 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Up to 4 single dose IV administrations (≤ 10 mL infused over approximately 1 minute) are planned, totaling less than 100 μg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ASP3662 administration (Part 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The dose levels used in part 2 will depend on the ongoing analysis of EO (enzyme occupancy) from previously dosed subjects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>[11C]AS2471907</intervention_name>
    <description>intravenous radiotracer</description>
    <arm_group_label>[11C]AS2471907 administration (Part 1)</arm_group_label>
    <other_name>Up to 4 single dose IV administrations (≤ 10 mL infused over approximately 1 minute) are planned</other_name>
    <other_name>totaling less than 100 μg.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Positron Emission Tomography (PET)</intervention_name>
    <description>Imaging scanning procedure</description>
    <arm_group_label>ASP3662 administration (Part 2)</arm_group_label>
    <arm_group_label>[11C]AS2471907 administration (Part 1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ASP3662</intervention_name>
    <description>oral</description>
    <arm_group_label>ASP3662 administration (Part 2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is of non-Asian descent.&#xD;
&#xD;
          -  Subject has a body mass index (BMI) range of 18.5 to 32 kg/m2, inclusive and weighs at&#xD;
             least 50 kg at screening.&#xD;
&#xD;
          -  Subject and his female spouse/partner who is of childbearing potential must be using&#xD;
             highly effective contraception1 consisting of 2 forms of birth control (at least one&#xD;
             of which must be a barrier method) starting at screening and continuing throughout the&#xD;
             study period and for 90 days after final study drug administration.&#xD;
&#xD;
          -  Subject must not donate sperm starting at screening, throughout the study period and&#xD;
             for at least 90 days after final study drug administration.&#xD;
&#xD;
          -  Subject agrees not to participate in another investigational study while on study&#xD;
             treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has a known or suspected hypersensitivity to ASP3662, [11C]AS2471907 or&#xD;
             intolerance of drugs with the same mechanism of action as ASP3662.&#xD;
&#xD;
          -  Subject has an allergy to topical anesthetics, such as, lidocaine (if used for&#xD;
             catheter placement).&#xD;
&#xD;
          -  Subject has previously participated in a clinical study with ASP3662 or part 1 of the&#xD;
             current study.&#xD;
&#xD;
          -  Subject has any of the liver enzymes (aspartate aminotransferase [AST], alanine&#xD;
             transaminase [ALT], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT]) or&#xD;
             total bilirubin (TBIL) above the upper limit of normal (ULN). If any liver enzyme is &gt;&#xD;
             1 x ULN but ≤ 1.5 x ULN, the assessment may be repeated once during the screening&#xD;
             period or on check-in. If the repeated assessment is above the ULN, it is&#xD;
             exclusionary. If the initial value is &gt; 1.5 x ULN, it cannot be repeated and is&#xD;
             exclusionary.&#xD;
&#xD;
          -  Subject has any clinically significant history of allergic conditions.&#xD;
&#xD;
          -  Subject with a history of a suicide attempt or suicidal behavior.&#xD;
&#xD;
          -  Subject has a history of smoking within the past 6 months.&#xD;
&#xD;
          -  Subject has any history or evidence of any clinically significant cardiovascular,&#xD;
             gastrointestinal (GI), endocrinologic, hematologic, hepatic, immunologic, metabolic,&#xD;
             urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major&#xD;
             disease or malignancy, as judged by the investigator or designee.&#xD;
&#xD;
          -  Subject has/had febrile illness or symptomatic viral, bacterial (including upper&#xD;
             respiratory infection) or fungal (non-cutaneous) infection within 1 week before clinic&#xD;
             check-in.&#xD;
&#xD;
          -  Subject has any clinically significant abnormality following the investigator's review&#xD;
             of the physical examination, electrocardiogram (ECG) and protocol-defined clinical&#xD;
             laboratory tests at screening or clinic check-in.&#xD;
&#xD;
          -  Subject has a mean pulse &lt; 40 or &gt; 90 beats per minute; mean systolic blood pressure &gt;&#xD;
             140 mmHg or mean diastolic blood pressure &gt; 90 mmHg (measurements taken in triplicate&#xD;
             after subject has been resting in supine position for 10 minutes) at screening. If the&#xD;
             mean pulse or mean systolic blood pressure (SBP) or mean diastolic blood pressure&#xD;
             (DBP) is out of the range specified above, 1 additional triplicate measurement may be&#xD;
             taken at screening.&#xD;
&#xD;
          -  Subject has a mean QTcF interval of &gt; 430 msec at screening or check-in. If the mean&#xD;
             QTcF exceeds the limits above, 1 additional triplicate ECG can be taken at screening.&#xD;
             If this triplicate also gives an abnormal result, the subject should be excluded.&#xD;
&#xD;
          -  Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac&#xD;
             arrhythmias or torsade de pointes, structural heart disease or a family history of&#xD;
             Long QT Syndrome.&#xD;
&#xD;
          -  Subject has use of any prescribed or non-prescribed drugs (including vitamins, natural&#xD;
             and herbal remedies, e.g., St. John's wort) in the 2 weeks before study drug&#xD;
             administration, except for occasional use of acetaminophen (up to 2 g/day).&#xD;
&#xD;
          -  Subject has history of consuming more than 14 units of alcoholic beverages per week&#xD;
             within 6 months prior to screening or has a history of alcoholism or drug/chemical or&#xD;
             substance abuse within the past 2 years prior to screening (Note: 1 unit = 12 ounces&#xD;
             of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests&#xD;
             positive at screening or clinic admission for alcohol or drugs of abuse (amphetamines,&#xD;
             barbiturates, benzodiazepines, cannabinoids, cocaine and opiates).&#xD;
&#xD;
          -  Subject has any use of drugs of abuse within 3 months before screening or check-in.&#xD;
&#xD;
          -  Subject has use of any inducer of metabolism (e.g., barbiturates, rifampin) in the 3&#xD;
             months prior to check-in.&#xD;
&#xD;
          -  Subject has consumed any caffeine-containing product within 24 hours prior to&#xD;
             admission or grapefruit or star fruit within 7 days prior to admission.&#xD;
&#xD;
          -  Subject has any significant blood loss, donated equal to 1 unit (450 mL) or more of&#xD;
             blood or received a transfusion of any blood or blood products within 60 days or&#xD;
             donated plasma within 7 days before check-in.&#xD;
&#xD;
          -  Subject has a positive serology test for hepatitis B surface antigen, anti-hepatitis A&#xD;
             virus (Immunoglobulin M), anti-hepatitis C virus or anti-human immunodeficiency virus&#xD;
             (HIV) Type 1 or Type 2 at screening.&#xD;
&#xD;
          -  Subject has participated in any interventional clinical study or has been treated with&#xD;
             any investigational drugs within 30 days or 5 half-lives, whichever is longer, before&#xD;
             the initiation of screening.&#xD;
&#xD;
          -  Subject is an employee of the Astellas Group or vendors involved in the study.&#xD;
&#xD;
          -  Additionally, a subject who meets the following imaging exclusion criteria will not be&#xD;
             included in this study:&#xD;
&#xD;
               -  Subject who suffers from claustrophobia.&#xD;
&#xD;
               -  Subject who has received a diagnostic or therapeutic radiopharmaceutical within 7&#xD;
                  days prior to participation in this study.&#xD;
&#xD;
               -  Participation in other research studies involving ionizing radiation within 1&#xD;
                  year of the PET scans that would cause the subject to exceed the US Nuclear&#xD;
                  Regulatory Commission yearly dose limits for healthy subjects, i.e., an effective&#xD;
                  dose of 5 Roentgen equivalent man (rem) received per year.&#xD;
&#xD;
               -  Subject with history of IV drug use which would prevent venous access for PET&#xD;
                  tracer injection.&#xD;
&#xD;
               -  Severe motor problems that prevent the subject from lying still for PET imaging.&#xD;
&#xD;
               -  Subject who has chronic pain for any reason (e.g., as the result of rheumatoid&#xD;
                  arthritis).&#xD;
&#xD;
               -  Subject who has an MRI scan deemed to be structurally abnormal by the&#xD;
                  investigator and thus precluding proper identification of the regions of interest&#xD;
                  (ROIs) (e.g., cortical atrophy). The MRI scan for an individual subject may be&#xD;
                  omitted if the required anatomical MRI scan for this subject is on file and was&#xD;
                  performed within approximately 6 months prior to dosing, as part of participation&#xD;
                  in an approved Yale Protocol.&#xD;
&#xD;
               -  Subjects who has current, past or anticipated exposure to radiation in the work&#xD;
                  place.&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>Senior Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Astellas Pharma Global Development, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Site US10001</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520-8-48</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>June 24, 2016</last_update_submitted>
  <last_update_submitted_qc>June 24, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>[11C]AS2471907</keyword>
  <keyword>ASP3662</keyword>
  <keyword>Positron Emission Tomography (PET)</keyword>
  <keyword>Brain enzyme occupancy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>AS2471907</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02194491
org study id: 3662-CL-0011
nct id: NCT02194491
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate a novel PET tracer ([11C]AS2471907), and to use
      [11C]AS2471907 to assess the level and time-course of enzyme occupancy in the human brain
      prior to and following single oral dose administration of ASP3662.
This is a two-part study where Part 1 will assess the test/retest variability of the ligand
      ([11C]AS2471907). Part 2 will assess the level and time-course of enzyme occupancy following
      ASP3662 dosing. Subjects will be confined to the clinic for up to 2 days.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Positron Emission Tomography measure: volume of distribution
time frame: Day 1 and 2 (Part 1 and Part 2)
measure: Positron Emission Tomography measure: brain time-activity curves
time frame: Day 1 and 2 (Part 1 and Part 2)
measure: Positron Emission Tomography measure: enzyme occupancy
time frame: Day 1 and 2 (Part 1 and Part 2)
measure: Positron Emission Tomography measure: binding potentials
time frame: Day 1 and 2 (Part 1 and Part 2)
measure: Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): AUClast (Part 2 only)
time frame: Day 1 and 2
description: Area under the plasma concentration - time curve from time zero to time of last measurable concentration (AUClast)
measure: Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): Cmax (Part 2 only)
time frame: Day 1 and 2
description: Maximum concentration (Cmax)
measure: Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): tmax (Part 2 only)
time frame: Day 1 and 2
description: Time to attain Cmax (tmax)
measure: Safety as assessed by laboratory tests, 12-lead electrocardiograms, vital signs, adverse events, physical exams, neurological exams and Columbia Suicide Severity Rating Scale
time frame: up to 9 days (Part 1 and Part 2)
arm group label: [11C]AS2471907 administration (Part 1)
arm group type: Experimental
description: Up to 4 single dose IV administrations (≤ 10 mL infused over approximately 1 minute) are planned, totaling less than 100 μg.
arm group label: ASP3662 administration (Part 2)
arm group type: Experimental
description: The dose levels used in part 2 will depend on the ongoing analysis of EO (enzyme occupancy) from previously dosed subjects.
intervention type: Other
intervention name: [11C]AS2471907
description: intravenous radiotracer
arm group label: [11C]AS2471907 administration (Part 1)
other name: Up to 4 single dose IV administrations (≤ 10 mL infused over approximately 1 minute) are planned
other name: totaling less than 100 μg.
intervention type: Radiation
intervention name: Positron Emission Tomography (PET)
description: Imaging scanning procedure
arm group label: ASP3662 administration (Part 2)
arm group label: [11C]AS2471907 administration (Part 1)
intervention type: Drug
intervention name: ASP3662
description: oral
arm group label: ASP3662 administration (Part 2)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Senior Medical Director
role: Study Director
affiliation: Astellas Pharma Global Development, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: AS2471907
sharing ipd: Undecided