<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/NCT01663961</url>
  </required_header>
  <id_info>
    <org_study_id>178-CL-059</org_study_id>
    <secondary_id>2008-000218-59</secondary_id>
    <nct_id>NCT01663961</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effect of a Single Dose of Digoxin on the Actions in the Bodies of Healthy Subjects After Having Taken Several Doses of YM178</brief_title>
  <official_title>An Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of YM178 on the Pharmacokinetics of Digoxin in Healthy Subjects</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>
      A study that evaluates the interaction in healthy subjects of the heart drug Digoxin on&#xD;
      YM178, when the latter is taken on a continuous basis, in order to establish that there is no&#xD;
      risk to patients who may take this combination of drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects receive a single oral dose of digoxin on Day 1. A full pharmacokinetic profile of&#xD;
      digoxin is obtained for up to 144 hours post-dose. On the morning of Day 7, after the&#xD;
      scheduled assessments are done, the subjects leave the clinic and return on Day 9.&#xD;
&#xD;
      From Day 10 up to and including Day 23, subjects receive daily oral doses of YM178 q.d. A&#xD;
      single dose of digoxin is given in combination with YM178 on Day 18 (8 days after the first&#xD;
      dose of YM178). On this day, a complete pharmacokinetic profile for digoxin is obtained up to&#xD;
      144 hours post-dose.&#xD;
&#xD;
      From Day 16 up to and including Day 19, blood samples for bioanalysis of YM178 are taken&#xD;
      regularly. In addition, vital signs, safety ECG (Electrocardiogram) measurements, safety&#xD;
      laboratory assessments, adverse events and concomitant medications are monitored throughout&#xD;
      the investigational period.&#xD;
&#xD;
      Subjects return for a Post Study Visit 7-14 days after the last dosing occasion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2008</start_date>
  <completion_date type="Actual">December 2008</completion_date>
  <primary_completion_date type="Actual">December 2008</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine the effects of steady state YM178 levels on the pharmacokinetics (PK) of a single dose of digoxin</measure>
    <time_frame>Pre-dose up to 144 hours post-dose</time_frame>
    <description>Cmax (Maximum concentration), AUCinf (Area under the plasma concentration - time curve extrapolated until time = infinity)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the interaction between YM178 and digoxin in terms of safety and tolerability through assessment of adverse events, ECG and clinical laboratory assessments</measure>
    <time_frame>Baseline to Post study visit (Up to 14 days after last dose)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>YM178 OCAS + digoxin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YM178 OCAS</intervention_name>
    <description>oral</description>
    <arm_group_label>YM178 OCAS + digoxin</arm_group_label>
    <other_name>Mirabegron</other_name>
    <other_name>Myrebtriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin</intervention_name>
    <description>oral</description>
    <arm_group_label>YM178 OCAS + digoxin</arm_group_label>
    <other_name>Lanoxin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female subject must be of non-child bearing potential, i.e. post menopausal,&#xD;
             surgically sterilized (e.g. tubal ligation), hysterectomy in medical history, or must&#xD;
             practice an adequate (double barrier) non-hormonal contraceptive method to prevent&#xD;
             pregnancies&#xD;
&#xD;
          -  Body Mass Index ≥ 18.5 and &lt; 30 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of cardiac diseases, including arrhythmias (including 1st and 2nd&#xD;
             degree atrioventricular heart blocks)&#xD;
&#xD;
          -  History of hypokalemia, hypercalcemia or hypomagnesemia&#xD;
&#xD;
          -  Any of the liver function tests (i.e. ALT, AST and Alkaline phosphatase) above the&#xD;
             upper limit of normal at repeated measures&#xD;
&#xD;
          -  Any clinically significant history of asthma, eczema, any other clinically significant&#xD;
             allergic condition or previous severe hypersensitivity to any drug (excluding&#xD;
             non-active hay fever)&#xD;
&#xD;
          -  Any clinically significant history of gastrointestinal symptoms in the 4 weeks prior&#xD;
             to admission to the clinical unit&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval after repeated measurements of &gt; 450&#xD;
             ms, a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias&#xD;
             or torsades de pointes, structural heart disease, or a family history of Long QT&#xD;
             Syndrome (LQTS)&#xD;
&#xD;
          -  Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3&#xD;
             months prior to admission to the clinical unit&#xD;
&#xD;
          -  Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2&#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>Clinical Study Manager</last_name>
    <role>Study Chair</role>
    <affiliation>Astellas Pharma Europe B.V.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SGS Aster</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>http://www.clinicaltrials.jp/user/ctrDetail_e.jsp?resultId=636</url>
    <description>Link to Results on JAPIC</description>
  </link>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>July 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <last_update_submitted>August 31, 2015</last_update_submitted>
  <last_update_submitted_qc>August 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>YM178 Oral Controlled Absorption System (OCAS)</keyword>
  <keyword>Digoxin (Lanoxin)</keyword>
  <keyword>DDI (Drug-drug interaction)</keyword>
  <keyword>Open-label</keyword>
  <keyword>Steady-state</keyword>
  <keyword>subjects</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Digoxin</mesh_term>
    <mesh_term>Mirabegron</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/NCT01663961
org study id: 178-CL-059
secondary id: 2008-000218-59
nct id: NCT01663961
lead sponsor: 
has dmc: No
A study that evaluates the interaction in healthy subjects of the heart drug Digoxin on
      YM178, when the latter is taken on a continuous basis, in order to establish that there is no
      risk to patients who may take this combination of drugs.
Subjects receive a single oral dose of digoxin on Day 1. A full pharmacokinetic profile of
      digoxin is obtained for up to 144 hours post-dose. On the morning of Day 7, after the
      scheduled assessments are done, the subjects leave the clinic and return on Day 9.

      From Day 10 up to and including Day 23, subjects receive daily oral doses of YM178 q.d. A
      single dose of digoxin is given in combination with YM178 on Day 18 (8 days after the first
      dose of YM178). On this day, a complete pharmacokinetic profile for digoxin is obtained up to
      144 hours post-dose.

      From Day 16 up to and including Day 19, blood samples for bioanalysis of YM178 are taken
      regularly. In addition, vital signs, safety ECG (Electrocardiogram) measurements, safety
      laboratory assessments, adverse events and concomitant medications are monitored throughout
      the investigational period.

      Subjects return for a Post Study Visit 7-14 days after the last dosing occasion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: To determine the effects of steady state YM178 levels on the pharmacokinetics (PK) of a single dose of digoxin
time frame: Pre-dose up to 144 hours post-dose
description: Cmax (Maximum concentration), AUCinf (Area under the plasma concentration - time curve extrapolated until time = infinity)
measure: To evaluate the interaction between YM178 and digoxin in terms of safety and tolerability through assessment of adverse events, ECG and clinical laboratory assessments
time frame: Baseline to Post study visit (Up to 14 days after last dose)
arm group label: YM178 OCAS + digoxin
arm group type: Experimental
intervention type: Drug
intervention name: YM178 OCAS
description: oral
arm group label: YM178 OCAS + digoxin
other name: Mirabegron
other name: Myrebtriq
intervention type: Drug
intervention name: Digoxin
description: oral
arm group label: YM178 OCAS + digoxin
other name: Lanoxin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Study Manager
role: Study Chair
affiliation: Astellas Pharma Europe B.V.
facility: 
country: France
url: http://www.clinicaltrials.jp/user/ctrDetail_e.jsp?resultId=636
description: Link to Results on JAPIC
responsible party type: Sponsor
mesh term: Digoxin
mesh term: Mirabegron