<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/NCT02220777</url>
  </required_header>
  <id_info>
    <org_study_id>8477-CL-0001</org_study_id>
    <secondary_id>2009-017865-42</secondary_id>
    <nct_id>NCT02220777</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Effects of Single Ascending Doses (SAD) of ASP8477, the Effect That Food Has on the Drug, and the Interaction Between ASP8477 and Omeprazole in Healthy Postmenopausal Females and Healthy Young Vasectomized Males</brief_title>
  <official_title>A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of ASP8477 in Healthy Postmenopausal Females and Healthy Young Vasectomized Males, Including a Food Effect Part and a Part to Investigate the Interaction Between ASP8477 and Omeprazole</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astellas Pharma Europe B.V.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astellas Pharma Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 4-part study. Part I assesses the safety and tolerability of single ascending doses&#xD;
      of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is&#xD;
      similar to part I except that the study is conducted in young, vasectomized males.&#xD;
&#xD;
      Part III assesses the effect of food (fed or fasted conditions) on ASP8477 in postmenopausal&#xD;
      subjects.&#xD;
&#xD;
      Part IV assesses the drug-drug interaction between ASP8477 and omeprazole in postmenopausal&#xD;
      subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part I (SAD) in healthy postmenopausal females evaluates the safety, and tolerability, and&#xD;
      defines Maximum Tolerated Dose = MTD, pharmacokinetics, and pharmacodynamics of single&#xD;
      ascending oral doses (SAD) of ASP8477. It is anticipated that around 7 doses are required to&#xD;
      cover the range from the safe starting dose until the MTD. Study medication is administered&#xD;
      under fasted conditions. Based on the safety, PK, and clinical observation of the subjects,&#xD;
      the dose escalation scheme may be adapted. Escalation to the next dose only proceeds after&#xD;
      review of the safety, tolerability, and PK from the previous treatment period.&#xD;
&#xD;
      Part II (SAD in young, healthy, vasectomized males) is similar to Part I, one cohort of 12&#xD;
      subjects are treated with two doses of ASP8477 plus placebo. The doses tested depend on the&#xD;
      safety data and pharmacodynamic profiles obtained in Part I, but is not expected to exceed&#xD;
      MTD. The rationale for this part is to bridge the data obtained in female subjects to male&#xD;
      subjects.&#xD;
&#xD;
      Part III (food effect) postmenopausal females receive ASP8477 once under fasted and once&#xD;
      under fed conditions in two separate periods in random order. The dose does not exceed 1/3 of&#xD;
      the MTD or, if that has not been reached, 1/3 of the highest tested dose in Part I. Subjects&#xD;
      stay in the clinic for 2 periods of 5 to 7 days (depending on the terminal half life,&#xD;
      resulting from Part I). Subjects are admitted on Day -2 per treatment period. Subjects'&#xD;
      feeding status is the same as on Day 1 of the same treatment period. Subjects are given a&#xD;
      single dose of ASP8477 under fed or fasting conditions on Day 1. After final discharge,&#xD;
      subjects return for an End of Study Visit (ESV) 5-9 days later.&#xD;
&#xD;
      Part IV (ASP8477-omeprazole drug-drug interaction) postmenopausal subjects are randomized to&#xD;
      receive omeprazole once alone and once with ASP8477 in two separate periods (in random&#xD;
      order). The dose of ASP8477 is the MTD or, if that is not been reached, the highest tested&#xD;
      dose in Part I. Omeprazole is chosen as target drug as it is a model substrate for CYP2C19&#xD;
      (accepted by FDA) and ASP8477 is known to have the strongest inhibitory effect on CYP2C19.&#xD;
      Subjects are admitted on Day -1 and stay for 2 periods of 4 days. Subjects are given a single&#xD;
      dose of omeprazole alone or with ASP8477 (in randomized order) on Day 1. Study medication is&#xD;
      administered under fasted conditions. Subjects are discharged on Day 3 and return for an ESV&#xD;
      5-9 days later.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2010</start_date>
  <completion_date type="Actual">May 2011</completion_date>
  <primary_completion_date type="Actual">May 2011</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety as assessed by recording adverse events, physical examination, laboratory assessments, vital signs, electrocardiograms (ECGs), cortisol levels, arterial carbon dioxide and oxygen saturation</measure>
    <time_frame>Day1 to End of Study Visit (5-9 days after final discharge)</time_frame>
    <description>For Part I and II Bond-Lader Visual Analogue Scale (VAS) and Bowdle VAS assessments will also be taken.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Maximum concentration (Cmax), in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Maximum concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Time to attain Cmax (tmax) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Time to attain Cmax (tmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Area Under the Curve (AUC) extrapolated until infinity (AUCinf) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Area Under the Curve (AUC) extrapolated until infinity (AUCinf)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by AUC until last sample taken (AUClast) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>AUC until last sample taken (AUClast), Absorption lag time (tlag), Apparent terminal elimination half-life (t1/2), Apparent volume of distribution (Vz/F), Apparent total body plasma clearance (CL/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Absorption lag time (tlag) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Absorption lag time (tlag)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent terminal elimination half-life (t1/2) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Apparent terminal elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent volume of distribution (Vz/F) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Apparent volume of distribution (Vz/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent total body plasma clearance (CL/F) in plasma</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Apparent total body plasma clearance (CL/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Amount excreted in urine until last sample (Aelast) in urine</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Amount excreted in urine until last sample (Aelast)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf) in urine</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%) in urine</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%) in urine</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The assessment of pharmacokinetic parameter of ASP8477 measured by Renal clearance (CLR) in urine</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Renal clearance (CLR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The assessment of pharmacokinetics of omeprazole measured by plasma concentration</measure>
    <time_frame>Day 1 to Day 3</time_frame>
    <description>Cmax, tmax, AUCinf, AUClast, t1/2, Vz/F, CL/F</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The assessment of pharmacodynamics of ASP8477 measured by serum concentration</measure>
    <time_frame>Day 1 to Day 4</time_frame>
    <description>serum concentration of endogenous substrates, volume of urine production, GFR and intra-ocular pressure</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Pharmacokinetics of ASP8477</condition>
  <condition>Pharmacodynamics of ASP8477</condition>
  <arm_group>
    <arm_group_label>1. ASP8477 and placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1: SAD in postmenopausal females and Part 2: SAD in vasectomized male</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2. ASP8477 alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3, fasted or fed</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3. omeprazole alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 4, Drug-Drug Interaction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4. ASP8477 + omeprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 4: Drug-Drug Interaction</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ASP8477</intervention_name>
    <description>oral</description>
    <arm_group_label>1. ASP8477 and placebo</arm_group_label>
    <arm_group_label>2. ASP8477 alone</arm_group_label>
    <arm_group_label>4. ASP8477 + omeprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>omeprazole</intervention_name>
    <description>oral</description>
    <arm_group_label>3. omeprazole alone</arm_group_label>
    <arm_group_label>4. ASP8477 + omeprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>oral</description>
    <arm_group_label>1. ASP8477 and placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy young (&lt;65 years of age at first planned dose) postmenopausal female (Parts I,&#xD;
             III, and IV).&#xD;
&#xD;
          -  Healthy young vasectomized male subject aged 18-55 years inclusive (Part II).&#xD;
&#xD;
          -  Body Mass index between 18.5 and 30.0 kg/m2 inclusive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or suspected hypersensitivity to ASP8477 or any of the components of the&#xD;
             formulations used.&#xD;
&#xD;
          -  Any of the liver function tests above the upper limit of normal.&#xD;
&#xD;
          -  A family history of psychiatric disorders.&#xD;
&#xD;
          -  Use of grapefruit (more than 3 x 200 ml) or marmalade (more than three times) in the&#xD;
             week prior to admission to the Clinical Unit, as reported by the subject.&#xD;
&#xD;
          -  Use of xanthine-containing beverages within 48 hours before admission.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Manager</last_name>
    <role>Study Chair</role>
    <affiliation>Astellas Pharma Europe B.V.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SGS Belgium N.V.</name>
      <address>
        <city>Antwerp</city>
        <zip>B-2060</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SGS Aster</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>August 18, 2014</last_update_submitted>
  <last_update_submitted_qc>August 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MTD (Maximum Tolerated Dose)</keyword>
  <keyword>Food effect</keyword>
  <keyword>Postmenopausal subjects</keyword>
  <keyword>Vasectomized subjects</keyword>
  <keyword>FIH (First In Humans)</keyword>
  <keyword>SAD (Single Ascending Dose)</keyword>
  <keyword>DDI (Drug-Drug Interaction)</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Omeprazole</mesh_term>
    <mesh_term>ASP8477</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02220777
org study id: 8477-CL-0001
secondary id: 2009-017865-42
nct id: NCT02220777
lead sponsor: 
has dmc: No
This is a 4-part study. Part I assesses the safety and tolerability of single ascending doses
      of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is
      similar to part I except that the study is conducted in young, vasectomized males.

      Part III assesses the effect of food (fed or fasted conditions) on ASP8477 in postmenopausal
      subjects.

      Part IV assesses the drug-drug interaction between ASP8477 and omeprazole in postmenopausal
      subjects.
Part I (SAD) in healthy postmenopausal females evaluates the safety, and tolerability, and
      defines Maximum Tolerated Dose = MTD, pharmacokinetics, and pharmacodynamics of single
      ascending oral doses (SAD) of ASP8477. It is anticipated that around 7 doses are required to
      cover the range from the safe starting dose until the MTD. Study medication is administered
      under fasted conditions. Based on the safety, PK, and clinical observation of the subjects,
      the dose escalation scheme may be adapted. Escalation to the next dose only proceeds after
      review of the safety, tolerability, and PK from the previous treatment period.

      Part II (SAD in young, healthy, vasectomized males) is similar to Part I, one cohort of 12
      subjects are treated with two doses of ASP8477 plus placebo. The doses tested depend on the
      safety data and pharmacodynamic profiles obtained in Part I, but is not expected to exceed
      MTD. The rationale for this part is to bridge the data obtained in female subjects to male
      subjects.

      Part III (food effect) postmenopausal females receive ASP8477 once under fasted and once
      under fed conditions in two separate periods in random order. The dose does not exceed 1/3 of
      the MTD or, if that has not been reached, 1/3 of the highest tested dose in Part I. Subjects
      stay in the clinic for 2 periods of 5 to 7 days (depending on the terminal half life,
      resulting from Part I). Subjects are admitted on Day -2 per treatment period. Subjects'
      feeding status is the same as on Day 1 of the same treatment period. Subjects are given a
      single dose of ASP8477 under fed or fasting conditions on Day 1. After final discharge,
      subjects return for an End of Study Visit (ESV) 5-9 days later.

      Part IV (ASP8477-omeprazole drug-drug interaction) postmenopausal subjects are randomized to
      receive omeprazole once alone and once with ASP8477 in two separate periods (in random
      order). The dose of ASP8477 is the MTD or, if that is not been reached, the highest tested
      dose in Part I. Omeprazole is chosen as target drug as it is a model substrate for CYP2C19
      (accepted by FDA) and ASP8477 is known to have the strongest inhibitory effect on CYP2C19.
      Subjects are admitted on Day -1 and stay for 2 periods of 4 days. Subjects are given a single
      dose of omeprazole alone or with ASP8477 (in randomized order) on Day 1. Study medication is
      administered under fasted conditions. Subjects are discharged on Day 3 and return for an ESV
      5-9 days later.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Safety as assessed by recording adverse events, physical examination, laboratory assessments, vital signs, electrocardiograms (ECGs), cortisol levels, arterial carbon dioxide and oxygen saturation
time frame: Day1 to End of Study Visit (5-9 days after final discharge)
description: For Part I and II Bond-Lader Visual Analogue Scale (VAS) and Bowdle VAS assessments will also be taken.
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Maximum concentration (Cmax), in plasma
time frame: Day 1 to Day 3
description: Maximum concentration (Cmax)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Time to attain Cmax (tmax) in plasma
time frame: Day 1 to Day 3
description: Time to attain Cmax (tmax)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Area Under the Curve (AUC) extrapolated until infinity (AUCinf) in plasma
time frame: Day 1 to Day 3
description: Area Under the Curve (AUC) extrapolated until infinity (AUCinf)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by AUC until last sample taken (AUClast) in plasma
time frame: Day 1 to Day 3
description: AUC until last sample taken (AUClast), Absorption lag time (tlag), Apparent terminal elimination half-life (t1/2), Apparent volume of distribution (Vz/F), Apparent total body plasma clearance (CL/F)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Absorption lag time (tlag) in plasma
time frame: Day 1 to Day 3
description: Absorption lag time (tlag)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent terminal elimination half-life (t1/2) in plasma
time frame: Day 1 to Day 3
description: Apparent terminal elimination half-life (t1/2)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent volume of distribution (Vz/F) in plasma
time frame: Day 1 to Day 3
description: Apparent volume of distribution (Vz/F)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent total body plasma clearance (CL/F) in plasma
time frame: Day 1 to Day 3
description: Apparent total body plasma clearance (CL/F)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Amount excreted in urine until last sample (Aelast) in urine
time frame: Day 1 to Day 3
description: Amount excreted in urine until last sample (Aelast)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf) in urine
time frame: Day 1 to Day 3
description: Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%) in urine
time frame: Day 1 to Day 3
description: Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%) in urine
time frame: Day 1 to Day 3
description: Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)
measure: The assessment of pharmacokinetic parameter of ASP8477 measured by Renal clearance (CLR) in urine
time frame: Day 1 to Day 3
description: Renal clearance (CLR)
measure: The assessment of pharmacokinetics of omeprazole measured by plasma concentration
time frame: Day 1 to Day 3
description: Cmax, tmax, AUCinf, AUClast, t1/2, Vz/F, CL/F
measure: The assessment of pharmacodynamics of ASP8477 measured by serum concentration
time frame: Day 1 to Day 4
description: serum concentration of endogenous substrates, volume of urine production, GFR and intra-ocular pressure
arm group label: 1. ASP8477 and placebo
arm group type: Experimental
description: Part 1: SAD in postmenopausal females and Part 2: SAD in vasectomized male
arm group label: 2. ASP8477 alone
arm group type: Experimental
description: Part 3, fasted or fed
arm group label: 3. omeprazole alone
arm group type: Experimental
description: Part 4, Drug-Drug Interaction
arm group label: 4. ASP8477 + omeprazole
arm group type: Experimental
description: Part 4: Drug-Drug Interaction
intervention type: Drug
intervention name: ASP8477
description: oral
arm group label: 1. ASP8477 and placebo
arm group label: 2. ASP8477 alone
arm group label: 4. ASP8477 + omeprazole
intervention type: Drug
intervention name: omeprazole
description: oral
arm group label: 3. omeprazole alone
arm group label: 4. ASP8477 + omeprazole
intervention type: Drug
intervention name: Placebo
description: oral
arm group label: 1. ASP8477 and placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Study Manager
role: Study Chair
affiliation: Astellas Pharma Europe B.V.
facility: 
facility: 
country: Belgium
country: France
responsible party type: Sponsor
mesh term: Omeprazole
mesh term: ASP8477