<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/NCT01711489</url>
  </required_header>
  <id_info>
    <org_study_id>9766-CL-0030</org_study_id>
    <nct_id>NCT01711489</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Mycophenolate Mofetil in Healthy Adult Subjects</brief_title>
  <official_title>A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Mycophenolate Mofetil in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astellas Pharma Global Development, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Basilea Pharmaceutica International Ltd</agency>
      <agency_class>Industry</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 assess the effect of multiple doses of isavuconazole on the&#xD;
      pharmacokinetics (PK) of mycophenolate mofetil (MMF) after single dose administration. Safety&#xD;
      and tolerability of isavuconazole will be assessed alone and in combination with MMF.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2012</start_date>
  <completion_date type="Actual">April 2012</completion_date>
  <primary_completion_date type="Actual">April 2012</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of pharmacokinetic (PK) variables of plasma mycophenolic acid (MPA) and phenolic glucuronide of MPA (MPAG): AUClast, AUCinf, Cmax</measure>
    <time_frame>Days 1 and 13: predose, and at 0.5, .75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose</time_frame>
    <description>Area under the concentration-time curve (AUC) from the time of dosing to the last quantifiable concentration (AUClast), AUC from the time of dosing to infinity (AUCinf), and maximum concentration (Cmax)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK of plasma isavuconazole: Trough concentration (Ctrough)</measure>
    <time_frame>Day 11, Days 14-16, predose and on Day 17, predose and 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK variables of plasma isavuconazole concentration: AUCtau, Cmax, and tmax</measure>
    <time_frame>Days 12 and 13: predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24 hours postdose</time_frame>
    <description>AUC during the time interval between consecutive dosing (AUCtau), time to attain Cmax (tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK variables of plasma MPA: tmax, t1/2, Vz/F, and CL/F</measure>
    <time_frame>Days 1 and 13: predose, and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose</time_frame>
    <description>Apparent terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent body clearance after oral dosing (CL/F)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK variables of plasma MPAG: tmax and t1/2</measure>
    <time_frame>Days 1 and 13: predose, and at 0.5, .75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessed through the reporting of adverse events, laboratory evaluations, electrocardiograms (ECGs) and vital signs</measure>
    <time_frame>Through Day 17</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Subjects</condition>
  <condition>Pharmacokinetics of Isavuconazole</condition>
  <condition>Pharmacokinetics of Plasma Mycophenolic Acid (MPA)</condition>
  <condition>Pharmacokinetics of Plasma Phenolic Glucuronide of MPA (MPAG)</condition>
  <arm_group>
    <arm_group_label>isavuconazole and mycophenolate mofetil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of MMF on Day 1, isavuconazole three times daily (TID) on Days 9 and 10, isavuconazole once daily (QD) Days 11-16, a single dose of MMF on Day 13</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>isavuconazole</intervention_name>
    <description>oral</description>
    <arm_group_label>isavuconazole and mycophenolate mofetil</arm_group_label>
    <other_name>BAL4815</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil</intervention_name>
    <description>oral</description>
    <arm_group_label>isavuconazole and mycophenolate mofetil</arm_group_label>
    <other_name>CellCept, MMF</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18&#xD;
             to 32 kg/m2, inclusive.&#xD;
&#xD;
          -  Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must&#xD;
             be ≤ 1.5 mg/dL&#xD;
&#xD;
          -  The female subject agrees to sexual abstinence, or is surgically sterile,&#xD;
             postmenopausal (defined as at least 2 years at Screening without menses), or using a&#xD;
             medically acceptable double barrier method (e.g. spermicide and diaphragm, or&#xD;
             spermicide and condom) to prevent pregnancy and agrees to continue using this method&#xD;
             from Screening until 5 weeks after the follow-up visit at the end of the study; and is&#xD;
             not lactating or pregnant as documented by negative pregnancy tests at Screening and&#xD;
             Day -1.&#xD;
&#xD;
          -  The male subject agrees to sexual abstinence, is surgically sterile, or is using a&#xD;
             medically acceptable method to prevent pregnancy and agrees to continue using this&#xD;
             method from Screening until 5 weeks after the follow-up visit at the end of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac&#xD;
             arrhythmia or torsade de pointes, structural heart disease, or family history of Long&#xD;
             QT syndrome (suggested by sudden death of a close relative at a young age due to&#xD;
             possible or probable cardiac causes).&#xD;
&#xD;
          -  The subject has a history of tuberculosis or exposure to anyone known or suspected to&#xD;
             have tuberculosis or any illness that might confound the results of the study or pose&#xD;
             additional risk in administering study drug to the subject.&#xD;
&#xD;
          -  The subject has a positive result for hepatitis C antibodies, hepatitis B surface&#xD;
             antigen, or QuantiFERON®-TB Gold test at Screening or is known to be positive for&#xD;
             human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  The subject has a known or suspected allergy to any of the components of the trial&#xD;
             products including mycophenolate mofetil (MMF) or the azole class of compounds, or a&#xD;
             history of multiple and/or severe allergies to drugs or foods, or a history of severe&#xD;
             anaphylactic reactions.&#xD;
&#xD;
          -  The subject is a smoker (any use of tobacco or nicotine containing products) within 6&#xD;
             months prior to Screening.&#xD;
&#xD;
          -  The subject has had treatment with prescription drugs or complementary and alternative&#xD;
             medicines within 14 days prior to Day -1, or over-the-counter medications within 1&#xD;
             week prior to Day -1, with the exception of acetaminophen up to 2 g/day.&#xD;
&#xD;
          -  The subject has a recent history (within the last 2 years) of drug or alcohol abuse,&#xD;
             as defined by the investigator, or a positive drug and/or alcohol screen&#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>Senior Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Astellas Pharma Global Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parexel International, LLC</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>October 18, 2012</last_update_submitted>
  <last_update_submitted_qc>October 18, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 22, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>isavuconazole</keyword>
  <keyword>mycophenolate mofetil (MMF)</keyword>
  <keyword>BAL8557</keyword>
  <keyword>BAL4815</keyword>
  <keyword>healthy volunteers</keyword>
  <keyword>Mycophenolic acid (MPA)</keyword>
  <keyword>Phenolic glucuronide of MPA (MPAG)</keyword>
  <keyword>CellCept</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Isavuconazole</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/NCT01711489
org study id: 9766-CL-0030
nct id: NCT01711489
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to assess the effect of multiple doses of isavuconazole on the
      pharmacokinetics (PK) of mycophenolate mofetil (MMF) after single dose administration. Safety
      and tolerability of isavuconazole will be assessed alone and in combination with MMF.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Composite of pharmacokinetic (PK) variables of plasma mycophenolic acid (MPA) and phenolic glucuronide of MPA (MPAG): AUClast, AUCinf, Cmax
time frame: Days 1 and 13: predose, and at 0.5, .75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose
description: Area under the concentration-time curve (AUC) from the time of dosing to the last quantifiable concentration (AUClast), AUC from the time of dosing to infinity (AUCinf), and maximum concentration (Cmax)
measure: PK of plasma isavuconazole: Trough concentration (Ctrough)
time frame: Day 11, Days 14-16, predose and on Day 17, predose and 24 hours postdose
measure: Composite of PK variables of plasma isavuconazole concentration: AUCtau, Cmax, and tmax
time frame: Days 12 and 13: predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24 hours postdose
description: AUC during the time interval between consecutive dosing (AUCtau), time to attain Cmax (tmax)
measure: Composite of PK variables of plasma MPA: tmax, t1/2, Vz/F, and CL/F
time frame: Days 1 and 13: predose, and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose
description: Apparent terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent body clearance after oral dosing (CL/F)
measure: Composite of PK variables of plasma MPAG: tmax and t1/2
time frame: Days 1 and 13: predose, and at 0.5, .75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose
measure: Safety assessed through the reporting of adverse events, laboratory evaluations, electrocardiograms (ECGs) and vital signs
time frame: Through Day 17
arm group label: isavuconazole and mycophenolate mofetil
arm group type: Experimental
description: Single dose of MMF on Day 1, isavuconazole three times daily (TID) on Days 9 and 10, isavuconazole once daily (QD) Days 11-16, a single dose of MMF on Day 13
intervention type: Drug
intervention name: isavuconazole
description: oral
arm group label: isavuconazole and mycophenolate mofetil
other name: BAL4815
intervention type: Drug
intervention name: Mycophenolate mofetil
description: oral
arm group label: isavuconazole and mycophenolate mofetil
other name: CellCept, MMF
criteria: 
gender: All
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
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mycophenolic Acid
mesh term: Isavuconazole