<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/NCT01660477</url>
  </required_header>
  <id_info>
    <org_study_id>9766-CL-0035</org_study_id>
    <nct_id>NCT01660477</nct_id>
  </id_info>
  <brief_title>Drug-drug Interaction Study Between Lopinavir/Ritonavir and Isavuconazole</brief_title>
  <official_title>A Phase 1, Open-Label, Parallel Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Multiple Doses of Lopinavir/Ritonavir and the Effects of Lopinavir/Ritonavir on the Pharmacokinetics of Multiple Doses of Isavuconazole 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 two part study is to assess the effect of multiple doses of isavuconazole&#xD;
      on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple&#xD;
      doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole.&#xD;
&#xD;
      Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or&#xD;
      isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate&#xD;
      safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir&#xD;
      on isavuconazole.&#xD;
&#xD;
      Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone,&#xD;
      lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">October 2012</completion_date>
  <primary_completion_date type="Actual">October 2012</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>Parallel Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) for isavuconazole: AUCtau</measure>
    <time_frame>Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose</time_frame>
    <description>(Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax</measure>
    <time_frame>Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose</time_frame>
    <description>(Arms 2 and 3) Maximum concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax</measure>
    <time_frame>Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose</time_frame>
    <description>(Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK for isavuconazole (in plasma): trough concentration (Ctrough)</measure>
    <time_frame>Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose</time_frame>
    <description>(Arms 1 and 3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK profile for isavuconazole (in plasma): Cmax, tmax</measure>
    <time_frame>Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose</time_frame>
    <description>(Arms 1 and 3) Time to attain Cmax (tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)</measure>
    <time_frame>Part 2, Days 3, 5, 7, 9 and 11: pre-dose</time_frame>
    <description>(Arms 2 and 3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK for lopinavir/ritonavir (in plasma): tmax</measure>
    <time_frame>Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose</time_frame>
    <description>(Arms 2 and 3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs</measure>
    <time_frame>Part 1, Days 1 - 20 ± 2</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Pharmacokinetics of Isavuconazole</condition>
  <condition>Pharmacokinetics of Lopinavir/Ritonavir</condition>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Arm 1: isavuconazole only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 : LPV/RTV only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3: isavuconazole and LPV/RTV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isavuconazole</intervention_name>
    <description>oral</description>
    <arm_group_label>Arm 1: isavuconazole only</arm_group_label>
    <arm_group_label>Arm 3: isavuconazole and LPV/RTV</arm_group_label>
    <other_name>BAL8557</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lopinavir/ritonavir</intervention_name>
    <description>oral</description>
    <arm_group_label>Arm 2 : LPV/RTV only</arm_group_label>
    <arm_group_label>Arm 3: isavuconazole and LPV/RTV</arm_group_label>
    <other_name>KALETRA®</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), total&#xD;
             bilirubin, lipase, amylase, glucose and triglycerides must be within the normal range&#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 3 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 3 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 pancreatitis&#xD;
&#xD;
          -  The subject has a positive result for hepatitis C antibodies, hepatitis B surface&#xD;
             antigen at Screening or is known to be positive for 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 lopinavir/ritonavir or the azole class of compounds, or a history&#xD;
             of multiple and/or severe allergies to drugs or foods (as judged by the investigator),&#xD;
             or a history of severe anaphylactic reactions- - The subject is a smoker (any use of&#xD;
             tobacco or nicotine containing products) within 6 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;
&#xD;
          -  The subject has participated in a previous isavuconazole study&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Astellas Pharma Global Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parexel International</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>February 2015</verification_date>
  <study_first_submitted>August 6, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2012</study_first_posted>
  <last_update_submitted>February 20, 2015</last_update_submitted>
  <last_update_submitted_qc>February 20, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 23, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Isavuconazole</keyword>
  <keyword>Lopinavir/ritonavir</keyword>
  <keyword>Healthy Volunteers</keyword>
  <keyword>BAL8557</keyword>
  <keyword>Kaletra ®</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Lopinavir</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/NCT01660477
org study id: 9766-CL-0035
nct id: NCT01660477
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this two part study is to assess the effect of multiple doses of isavuconazole
      on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple
      doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole.

      Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or
      isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate
      safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir
      on isavuconazole.

      Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone,
      lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.
allocation: Randomized
intervention model: Parallel Assignment
masking: None (Open Label)
measure: Pharmacokinetic (PK) for isavuconazole: AUCtau
time frame: Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose
description: (Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)
measure: Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax
time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose
description: (Arms 2 and 3) Maximum concentration (Cmax)
measure: Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax
time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose
description: (Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)
measure: PK for isavuconazole (in plasma): trough concentration (Ctrough)
time frame: Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose
description: (Arms 1 and 3)
measure: PK profile for isavuconazole (in plasma): Cmax, tmax
time frame: Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose
description: (Arms 1 and 3) Time to attain Cmax (tmax)
measure: PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)
time frame: Part 2, Days 3, 5, 7, 9 and 11: pre-dose
description: (Arms 2 and 3)
measure: PK for lopinavir/ritonavir (in plasma): tmax
time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose
description: (Arms 2 and 3)
measure: Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
time frame: Part 1, Days 1 - 20 ± 2
arm group label: Arm 1: isavuconazole only
arm group type: Experimental
description: Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13
arm group label: Arm 2 : LPV/RTV only
arm group type: Experimental
description: Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13
arm group label: Arm 3: isavuconazole and LPV/RTV
arm group type: Experimental
description: Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13
intervention type: Drug
intervention name: Isavuconazole
description: oral
arm group label: Arm 1: isavuconazole only
arm group label: Arm 3: isavuconazole and LPV/RTV
other name: BAL8557
intervention type: Drug
intervention name: Lopinavir/ritonavir
description: oral
arm group label: Arm 2 : LPV/RTV only
arm group label: Arm 3: isavuconazole and LPV/RTV
other name: KALETRA®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Director
role: Study Director
affiliation: Astellas Pharma Global Development
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ritonavir
mesh term: Lopinavir
mesh term: Isavuconazole