<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/NCT03777761</url>
  </required_header>
  <id_info>
    <org_study_id>ONT-380-011</org_study_id>
    <nct_id>NCT03777761</nct_id>
  </id_info>
  <brief_title>Effects of Tucatinib on Cardiac Repolarization in Healthy Participants</brief_title>
  <official_title>A Phase 1, Randomized, Partially Double-Blind, Placebo- and Positive-controlled Study to Evaluate the Effect of Tucatinib on Cardiac Repolarization in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seagen Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is looking at how the study drug, tucatinib, affects the heart. Tucatinib is being&#xD;
      studied as a possible treatment for breast cancer. This study will recruit healthy&#xD;
      volunteers. There are 3 parts in the study. Each volunteer will be in all 3 parts. One part&#xD;
      will be to take the study drug, the second part will be to take a placebo (pill with no&#xD;
      medicine), and the third part will be to take moxifloxacin. The volunteers will only know&#xD;
      what part of the study they are in when they take moxifloxacin. For the study drug and&#xD;
      placebo parts, volunteers will take 2 pills by mouth for 5 days. For the moxifloxacin part,&#xD;
      volunteers will take 1 pill by mouth for 1 day.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the effects of a steady state therapeutic dose of tucatinib on QTcF&#xD;
      (QT interval corrected for heart rate using Fridericia's method) in healthy individuals. In&#xD;
      this design, study treatment will be dosed in 3 sequential treatment periods:&#xD;
&#xD;
      Treatment A: Oral doses of 300mg tucatinib for 5 days&#xD;
&#xD;
      Treatment B: Oral doses of matching placebo for tucatinib for 5 days&#xD;
&#xD;
      Treatment C: A single oral dose of 400 mg of moxifloxacin&#xD;
&#xD;
      Patients will be randomized based on 2-Williams-square design to 1 of 6 treatment sequences&#xD;
      to maintain the study blind for tucatinib and placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2018</start_date>
  <completion_date type="Actual">March 11, 2019</completion_date>
  <primary_completion_date type="Actual">March 11, 2019</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The study will be double-blind in regard to tucatinib and placebo study treatments and open-label for the positive control, moxifloxacin.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Placebo-corrected change-from-baseline in QTcF</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>QTcF is the QT interval corrected for heart rate using Fridericia's method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in heart rate (HR)</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in PR interval</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QRS interval</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placebo-corrected change from baseline in HR</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placebo-corrected change from baseline in PR interval</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placebo-corrected change from baseline in QRS interval</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Number of participants who experience increases in absolute QTcF interval values &gt;450 msec</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Number of participants who experience QTcF interval changes from predose baseline of &gt;30msec</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Number of participants who experience an increase in PR interval from predose baseline of &gt;25% to a PR &gt;200 msec</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Number of participants who experience an increase in QRS interval from predose baseline &gt;25% to a QRS &gt;120 msec</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Number of participants who experience a decrease in heart rate &gt;25% from baseline to a heart rate &lt;50</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Number of participants who experience an increase in heart rate &gt;25% from baseline to a heart rate &gt;100</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of treatment-emergent changes of T-wave morphology and U-wave presence</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUC[0-inf]) for tucatinib and ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC from time 0 to the time of the last quantifiable concentration for tucatinib and ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AUC[0-inf] due to extrapolation for tucatinib and ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration for tucatinib and ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum observed concentration for tucatinib and ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal elimination half-life for tucatinib and ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total clearance for tucatinib</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase for tucatinib</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic ratio based on AUC for ONT-993</measure>
    <time_frame>Up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (AEs)</measure>
    <time_frame>Up to 32 days</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment Sequence ABC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>tucatinib + placebo + moxifloxacin (administered in sequential treatment periods)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence CAB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>moxifloxacin + tucatinib + placebo (administered in sequential treatment periods)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence BCA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>placebo + moxifloxacin + tucatinib (administered in sequential treatment periods)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence CBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>moxifloxacin + placebo + tucatinib (administered in sequential treatment periods)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence ACB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>tucatinib + moxifloxacin + placebo (administered in sequential treatment periods)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence BAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>placebo + tucatinib + moxifloxacin (administered in sequential treatment periods)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tucatinib</intervention_name>
    <description>300mg oral dose</description>
    <arm_group_label>Treatment Sequence ABC</arm_group_label>
    <arm_group_label>Treatment Sequence ACB</arm_group_label>
    <arm_group_label>Treatment Sequence BAC</arm_group_label>
    <arm_group_label>Treatment Sequence BCA</arm_group_label>
    <arm_group_label>Treatment Sequence CAB</arm_group_label>
    <arm_group_label>Treatment Sequence CBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Matching placebo for tucatinib</description>
    <arm_group_label>Treatment Sequence ABC</arm_group_label>
    <arm_group_label>Treatment Sequence ACB</arm_group_label>
    <arm_group_label>Treatment Sequence BAC</arm_group_label>
    <arm_group_label>Treatment Sequence BCA</arm_group_label>
    <arm_group_label>Treatment Sequence CAB</arm_group_label>
    <arm_group_label>Treatment Sequence CBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>moxifloxacin</intervention_name>
    <description>400mg single oral dose</description>
    <arm_group_label>Treatment Sequence ABC</arm_group_label>
    <arm_group_label>Treatment Sequence ACB</arm_group_label>
    <arm_group_label>Treatment Sequence BAC</arm_group_label>
    <arm_group_label>Treatment Sequence BCA</arm_group_label>
    <arm_group_label>Treatment Sequence CAB</arm_group_label>
    <arm_group_label>Treatment Sequence CBA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Good health, determined by medical history, physical examination, 12-lead ECG, vital&#xD;
             signs measurements, or clinical laboratory evaluations&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 32 kg/m^2&#xD;
&#xD;
          -  Body weight between 50 and 100 kg&#xD;
&#xD;
          -  Female subjects must be of non-childbearing potential&#xD;
&#xD;
          -  Male subjects must agree to use contraception or be surgically sterile for at least 90&#xD;
             days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant history of any metabolic, allergic, dermatological, hepatic, renal,&#xD;
             hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory,&#xD;
             endocrine, or psychiatric disorder&#xD;
&#xD;
          -  Any condition affecting drug absorption&#xD;
&#xD;
          -  History of hypersensitivity or allergy to any drug compound, food, or other substance&#xD;
&#xD;
          -  Single 12-lead ECG demonstrating QTcF &gt;450 msec for males or &gt;470 msec for females, or&#xD;
             history/evidence of long QT syndrome&#xD;
&#xD;
          -  History of alcoholism or drug/chemical abuse within 2 years&#xD;
&#xD;
          -  Use of prescription products within 30 days prior to check in&#xD;
&#xD;
          -  Use of nonprescription products within 14 days prior to check in, including vitamins,&#xD;
             minerals, and herbal supplements&#xD;
&#xD;
          -  Use of tobacco- or nicotine-containing products within 3 months prior to check in&#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>Joseph Woolery, PharmD, BCOP</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Clinical Research Unit - Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75247</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>April 11, 2019</last_update_submitted>
  <last_update_submitted_qc>April 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>Tucatinib</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/NCT03777761
org study id: ONT-380-011
nct id: NCT03777761
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study is looking at how the study drug, tucatinib, affects the heart. Tucatinib is being
      studied as a possible treatment for breast cancer. This study will recruit healthy
      volunteers. There are 3 parts in the study. Each volunteer will be in all 3 parts. One part
      will be to take the study drug, the second part will be to take a placebo (pill with no
      medicine), and the third part will be to take moxifloxacin. The volunteers will only know
      what part of the study they are in when they take moxifloxacin. For the study drug and
      placebo parts, volunteers will take 2 pills by mouth for 5 days. For the moxifloxacin part,
      volunteers will take 1 pill by mouth for 1 day.
This study will evaluate the effects of a steady state therapeutic dose of tucatinib on QTcF
      (QT interval corrected for heart rate using Fridericia's method) in healthy individuals. In
      this design, study treatment will be dosed in 3 sequential treatment periods:

      Treatment A: Oral doses of 300mg tucatinib for 5 days

      Treatment B: Oral doses of matching placebo for tucatinib for 5 days

      Treatment C: A single oral dose of 400 mg of moxifloxacin

      Patients will be randomized based on 2-Williams-square design to 1 of 6 treatment sequences
      to maintain the study blind for tucatinib and placebo.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: The study will be double-blind in regard to tucatinib and placebo study treatments and open-label for the positive control, moxifloxacin.
measure: Placebo-corrected change-from-baseline in QTcF
time frame: Up to 32 days
description: QTcF is the QT interval corrected for heart rate using Fridericia's method.
measure: Change from baseline in heart rate (HR)
time frame: Up to 32 days
measure: Change from baseline in QTcF
time frame: Up to 32 days
measure: Change from baseline in PR interval
time frame: Up to 32 days
measure: Change from baseline in QRS interval
time frame: Up to 32 days
measure: Placebo-corrected change from baseline in HR
time frame: Up to 32 days
measure: Placebo-corrected change from baseline in PR interval
time frame: Up to 32 days
measure: Placebo-corrected change from baseline in QRS interval
time frame: Up to 32 days
measure: • Number of participants who experience increases in absolute QTcF interval values >450 msec
time frame: Up to 32 days
measure: • Number of participants who experience QTcF interval changes from predose baseline of >30msec
time frame: Up to 32 days
measure: • Number of participants who experience an increase in PR interval from predose baseline of >25% to a PR >200 msec
time frame: Up to 32 days
measure: • Number of participants who experience an increase in QRS interval from predose baseline >25% to a QRS >120 msec
time frame: Up to 32 days
measure: • Number of participants who experience a decrease in heart rate >25% from baseline to a heart rate <50
time frame: Up to 32 days
measure: • Number of participants who experience an increase in heart rate >25% from baseline to a heart rate >100
time frame: Up to 32 days
measure: Frequency of treatment-emergent changes of T-wave morphology and U-wave presence
time frame: Up to 32 days
measure: Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUC[0-inf]) for tucatinib and ONT-993
time frame: Up to 26 days
measure: AUC from time 0 to the time of the last quantifiable concentration for tucatinib and ONT-993
time frame: Up to 26 days
measure: Percentage of AUC[0-inf] due to extrapolation for tucatinib and ONT-993
time frame: Up to 26 days
measure: Maximum observed concentration for tucatinib and ONT-993
time frame: Up to 26 days
measure: Time of maximum observed concentration for tucatinib and ONT-993
time frame: Up to 26 days
measure: Apparent terminal elimination half-life for tucatinib and ONT-993
time frame: Up to 26 days
measure: Apparent total clearance for tucatinib
time frame: Up to 26 days
measure: Apparent volume of distribution during the terminal phase for tucatinib
time frame: Up to 26 days
measure: Metabolic ratio based on AUC for ONT-993
time frame: Up to 26 days
measure: Incidence of adverse events (AEs)
time frame: Up to 32 days
arm group label: Treatment Sequence ABC
arm group type: Experimental
description: tucatinib + placebo + moxifloxacin (administered in sequential treatment periods)
arm group label: Treatment Sequence CAB
arm group type: Experimental
description: moxifloxacin + tucatinib + placebo (administered in sequential treatment periods)
arm group label: Treatment Sequence BCA
arm group type: Experimental
description: placebo + moxifloxacin + tucatinib (administered in sequential treatment periods)
arm group label: Treatment Sequence CBA
arm group type: Experimental
description: moxifloxacin + placebo + tucatinib (administered in sequential treatment periods)
arm group label: Treatment Sequence ACB
arm group type: Experimental
description: tucatinib + moxifloxacin + placebo (administered in sequential treatment periods)
arm group label: Treatment Sequence BAC
arm group type: Experimental
description: placebo + tucatinib + moxifloxacin (administered in sequential treatment periods)
intervention type: Drug
intervention name: tucatinib
description: 300mg oral dose
arm group label: Treatment Sequence ABC
arm group label: Treatment Sequence ACB
arm group label: Treatment Sequence BAC
arm group label: Treatment Sequence BCA
arm group label: Treatment Sequence CAB
arm group label: Treatment Sequence CBA
intervention type: Drug
intervention name: placebo
description: Matching placebo for tucatinib
arm group label: Treatment Sequence ABC
arm group label: Treatment Sequence ACB
arm group label: Treatment Sequence BAC
arm group label: Treatment Sequence BCA
arm group label: Treatment Sequence CAB
arm group label: Treatment Sequence CBA
intervention type: Drug
intervention name: moxifloxacin
description: 400mg single oral dose
arm group label: Treatment Sequence ABC
arm group label: Treatment Sequence ACB
arm group label: Treatment Sequence BAC
arm group label: Treatment Sequence BCA
arm group label: Treatment Sequence CAB
arm group label: Treatment Sequence CBA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Joseph Woolery, PharmD, BCOP
role: Study Director
affiliation: Seagen Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Moxifloxacin
mesh term: Tucatinib