<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/NCT03826602</url>
  </required_header>
  <id_info>
    <org_study_id>SGNTUC-020</org_study_id>
    <nct_id>NCT03826602</nct_id>
  </id_info>
  <brief_title>A Drug-Drug Interaction Study in Healthy Volunteers of the Effects of Tucatinib on Metformin</brief_title>
  <official_title>A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study to Evaluate the Effects of Tucatinib of the Pharmacokinetics of Metformin in Healthy Male and Female Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seagen Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <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 being done to look at how tucatinib might affect the way another drug&#xD;
      (metformin) works. It will look at healthy volunteers and how tucatinib affects how the body&#xD;
      absorbs metformin. This will help us find out whether tucatinib is safe to give together with&#xD;
      metformin. The study will also look at how tucatinib affects how the kidneys work.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, fixed-sequence, drug-drug interaction study to assess the effects of&#xD;
      multiple oral doses of tucatinib on the pharmacokinetics of a single oral dose of metformin&#xD;
      in healthy subjects. The primary objective of the study is to assess the effects of tucatinib&#xD;
      on the single-dose PK of metformin. Secondary objectives of the study are to (1) assess the&#xD;
      safety and tolerability of metformin when coadministered with tucatinib and (2) assess the&#xD;
      effects of tucatinib on renal function using iohexol as glomerular filtration rate (GFR)&#xD;
      marker.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Actual">March 15, 2019</completion_date>
  <primary_completion_date type="Actual">March 8, 2019</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to maximum observed plasma concentration (tmax) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Half-life (t1/2) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve from time 0 to the last available measurement (AUC0-last) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration time curve to time 0 extrapolated to infinity (AUC0-inf) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution (V2/F) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Oral clearance (CL/F) of metformin</measure>
    <time_frame>Up to 9 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (as assessed by AE assessments, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead electrocardiogram)</measure>
    <time_frame>Up to 16 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance</measure>
    <time_frame>Up to 8 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Drug-drug Interaction</condition>
  <arm_group>
    <arm_group_label>Tucatinib plus metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib administered twice daily on Days 2-8. Metformin administered as a single dose on Days 1 and 8. Iohexol administered via IV push on Days 1 and 8</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tucatinib</intervention_name>
    <description>150mg administered orally twice daily</description>
    <arm_group_label>Tucatinib plus metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>850mg administered orally</description>
    <arm_group_label>Tucatinib plus metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iohexol</intervention_name>
    <description>1500 mg administered intravenously (IV)</description>
    <arm_group_label>Tucatinib plus metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy status, as defined by the absence of evidence of any clinically significant&#xD;
             findings&#xD;
&#xD;
          -  Males must agree to use a barrier method of birth control and not donate sperm during&#xD;
             study plus 30 days after last dose of study drug&#xD;
&#xD;
          -  Weight of ≥60kg&#xD;
&#xD;
          -  Body mass index between 18.0 and 32.0 kg/m² (inclusive)&#xD;
&#xD;
          -  Ability to abstain from alcohol-, caffeine-, and xanthine-containing food and&#xD;
             beverages from 48 hours prior to admission through study discharge&#xD;
&#xD;
          -  All nonregular medication (including over-the-counter medication, health supplements,&#xD;
             and herbal remedies) must be stopped at least 28 days prior to admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females who are of childbearing potential or lactating&#xD;
&#xD;
          -  Males with female partners who are pregnant, lactating, or planning to become pregnant&#xD;
             within 30 days of the study&#xD;
&#xD;
          -  Use of any investigational drug or device within 30 days of study start&#xD;
&#xD;
          -  Use of tobacco products within 21 days prior to admission&#xD;
&#xD;
          -  Routine or chronic use of more than 3 grams of acetaminophen daily&#xD;
&#xD;
          -  Strenuous activity, sunbathing, and contact sports within 72 hours prior to first&#xD;
             admission and for the duration of the study&#xD;
&#xD;
          -  Blood transfusion within 90 days of study drug administration&#xD;
&#xD;
          -  History of alcoholism or drug abuse within 2 years&#xD;
&#xD;
          -  History of alcohol consumption exceeding 7 drinks/week for female participants or 14&#xD;
             drinks/week for male subjects&#xD;
&#xD;
          -  History of donation of more than 450 mL of blood within 60 days prior to dosing, or&#xD;
             planned donation before 30 days have elapsed since intake of study drug&#xD;
&#xD;
          -  Plasma or platelet donation within 7 days of initial study drug administration&#xD;
&#xD;
          -  Positive screening test for Hepatitis B, Hepatitis C, or HIV 1 or 2 (human&#xD;
             immunodeficiency virus)&#xD;
&#xD;
          -  Acute or chronic metabolic acidosis, including diabetic ketoacidosis&#xD;
&#xD;
          -  Renal disease or dysfunction as suggested by serum creatinine levels or abnormal&#xD;
             creatinine clearance&#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>JoAl Mayor, PharmD, BCOP</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pharmaceutical Research Associates</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>March 25, 2019</last_update_submitted>
  <last_update_submitted_qc>March 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 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>Metformin</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/NCT03826602
org study id: SGNTUC-020
nct id: NCT03826602
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is being done to look at how tucatinib might affect the way another drug
      (metformin) works. It will look at healthy volunteers and how tucatinib affects how the body
      absorbs metformin. This will help us find out whether tucatinib is safe to give together with
      metformin. The study will also look at how tucatinib affects how the kidneys work.
This is a single center, fixed-sequence, drug-drug interaction study to assess the effects of
      multiple oral doses of tucatinib on the pharmacokinetics of a single oral dose of metformin
      in healthy subjects. The primary objective of the study is to assess the effects of tucatinib
      on the single-dose PK of metformin. Secondary objectives of the study are to (1) assess the
      safety and tolerability of metformin when coadministered with tucatinib and (2) assess the
      effects of tucatinib on renal function using iohexol as glomerular filtration rate (GFR)
      marker.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum observed plasma concentration (Cmax) of metformin
time frame: Up to 9 days
measure: Time to maximum observed plasma concentration (tmax) of metformin
time frame: Up to 9 days
measure: Half-life (t1/2) of metformin
time frame: Up to 9 days
measure: Area under the plasma concentration-time curve from time 0 to the last available measurement (AUC0-last) of metformin
time frame: Up to 9 days
measure: Area under the plasma concentration time curve to time 0 extrapolated to infinity (AUC0-inf) of metformin
time frame: Up to 9 days
measure: Apparent volume of distribution (V2/F) of metformin
time frame: Up to 9 days
measure: Oral clearance (CL/F) of metformin
time frame: Up to 9 days
measure: Incidence of adverse events (as assessed by AE assessments, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead electrocardiogram)
time frame: Up to 16 days
measure: Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance
time frame: Up to 8 days
arm group label: Tucatinib plus metformin
arm group type: Experimental
description: Tucatinib administered twice daily on Days 2-8. Metformin administered as a single dose on Days 1 and 8. Iohexol administered via IV push on Days 1 and 8
intervention type: Drug
intervention name: Tucatinib
description: 150mg administered orally twice daily
arm group label: Tucatinib plus metformin
intervention type: Drug
intervention name: Metformin
description: 850mg administered orally
arm group label: Tucatinib plus metformin
intervention type: Drug
intervention name: Iohexol
description: 1500 mg administered intravenously (IV)
arm group label: Tucatinib plus metformin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: JoAl Mayor, PharmD, BCOP
role: Study Director
affiliation: Seagen Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Metformin
mesh term: Tucatinib