<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/NCT02243150</url>
  </required_header>
  <id_info>
    <org_study_id>G1T28-1-01</org_study_id>
    <nct_id>NCT02243150</nct_id>
  </id_info>
  <brief_title>Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1</brief_title>
  <official_title>First-In-Human Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of G1T28-1 in Healthy Male and Female Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>G1 Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>G1 Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This first-in-human (FIH) study will provide the first safety, PK, and PD data of G1T28-1 in&#xD;
      humans and will allow further development of G1T28 1 in patients with cancer to reduce&#xD;
      chemotherapy-induced myelosuppression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 18, 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</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>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Up to day 14</time_frame>
    <description>All Adverse events, including-clinical laboratory data, vital signs and ECGs will be analyzed in all subjects receiving study drug through 14 days post dose of study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)</measure>
    <time_frame>Day 1, Day 2, Day 3 and Day 4</time_frame>
    <description>The observed peak plasma concentration determined from the plasma concentration vs. time data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax)</measure>
    <time_frame>Day 1, Day 2, Day 3 and Day 4</time_frame>
    <description>The time to reach the observed peak plasma concentration from the plasma concentration vs. time data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12)</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours post dosing, calculated by linear/log trapezoidal method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration- time curve from 0 to last (AUC 0-last)</measure>
    <time_frame>Day 1, Day 2, Day 3, Day 4</time_frame>
    <description>Area under the plasma concentration-time curve from time 0 to time of last measurable concentration calculated by linear/log trapezoidal method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration-time curve from time zero to infinity</measure>
    <time_frame>Day 1, Day 2, Day 3, Day 4</time_frame>
    <description>Area under the concentration time curve from time zero extrapolated to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2)</measure>
    <time_frame>Day 1</time_frame>
    <description>Terminal half-life, defined as 0.693 divided by λzλ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant</measure>
    <time_frame>Day 1</time_frame>
    <description>Determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Clearance</measure>
    <time_frame>Day 1</time_frame>
    <description>Clearance after intravenous administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution</measure>
    <time_frame>Day 1</time_frame>
    <description>Volume of distribution in the terminal elimination phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics-Whole Blood Ex Vivo Stimulation</measure>
    <time_frame>Day 1</time_frame>
    <description>Analysis of peripheral blood cell proliferation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic - Bone Marrow Analysis</measure>
    <time_frame>Day 1</time_frame>
    <description>Analysis of hematopoietic stem and progenitor cell (HSPC)</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 1; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 2; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 3; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 4; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 5; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 7 - Bone Marrow Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this cohort will receive active drug, G1T28-1. Dose of G1T28-1 will be determined based on the safety and PK data from previous cohorts. G1T28-1 will be administered in 50mL of 5% dextrose by IV infusion. Subjects in this cohort will be selected for the Ex-Vivo Stimulation group and will have a one time bone marrow aspirate at one of the following time points: pre dose, 12 or 24 hours post dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>G1T28-1 (CDK 4/6 Inhibitor)</intervention_name>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_label>Cohort 6</arm_group_label>
    <arm_group_label>Cohort 7 - Bone Marrow Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_label>Cohort 6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female volunteers, 18-60 years of age; no clinically significant&#xD;
             findings reported following detailed physical examination, medical history, vital&#xD;
             signs, clinical laboratory tests, and ECGs as deemed by the PI&#xD;
&#xD;
          -  Body mass index (BMI) in the range of 18 to 32 kg/m2 (inclusive) and weighing at least&#xD;
             50 kg&#xD;
&#xD;
          -  Non-smokers / non-users of nicotine containing products for at least the previous 3&#xD;
             months&#xD;
&#xD;
          -  Agreement to use birth control during the study and 3 months post last visit&#xD;
&#xD;
          -  Able to comply with all protocol requirements and procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant abnormalities found during physical examination, medical&#xD;
             history review, ECGs (including QTcf interval &gt; 450 msec), vital signs and laboratory&#xD;
             tests (including positive test for HIV, hepatitis B and/or C)&#xD;
&#xD;
          -  History of any serious allergic reaction to any medication&#xD;
&#xD;
          -  Participated in a previous clinical trial with an investigational product in the last&#xD;
             60 days&#xD;
&#xD;
          -  Any blood or plasma donation or other loss of blood at a volume exceeding 500 mL&#xD;
             within 3 months before dosing&#xD;
&#xD;
          -  History of drug or alcohol abuse in the last 2 years and positive test for drug abuse&#xD;
&#xD;
          -  Use of any systemic medication within the past 2 weeks, including use of herbal&#xD;
             products&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Any other issue which, in the opinion of the PI, will make the subject ineligible for&#xD;
             study participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Renger Tiessen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PRA Clinic Netherlands</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PRA Early Development Clinic</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>December 14, 2018</last_update_submitted>
  <last_update_submitted_qc>December 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02243150
org study id: G1T28-1-01
nct id: NCT02243150
lead sponsor: 
has dmc: No
This first-in-human (FIH) study will provide the first safety, PK, and PD data of G1T28-1 in
      humans and will allow further development of G1T28 1 in patients with cancer to reduce
      chemotherapy-induced myelosuppression.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Adverse Events
time frame: Up to day 14
description: All Adverse events, including-clinical laboratory data, vital signs and ECGs will be analyzed in all subjects receiving study drug through 14 days post dose of study drug.
measure: Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)
time frame: Day 1, Day 2, Day 3 and Day 4
description: The observed peak plasma concentration determined from the plasma concentration vs. time data
measure: Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax)
time frame: Day 1, Day 2, Day 3 and Day 4
description: The time to reach the observed peak plasma concentration from the plasma concentration vs. time data
measure: Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12)
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to 12 hours post dosing, calculated by linear/log trapezoidal method
measure: Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration- time curve from 0 to last (AUC 0-last)
time frame: Day 1, Day 2, Day 3, Day 4
description: Area under the plasma concentration-time curve from time 0 to time of last measurable concentration calculated by linear/log trapezoidal method
measure: Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration-time curve from time zero to infinity
time frame: Day 1, Day 2, Day 3, Day 4
description: Area under the concentration time curve from time zero extrapolated to infinity
measure: Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2)
time frame: Day 1
description: Terminal half-life, defined as 0.693 divided by λzλ
measure: Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant
time frame: Day 1
description: Determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.
measure: Pharmacokinetics of G1T28-1 in Plasma: Clearance
time frame: Day 1
description: Clearance after intravenous administration
measure: Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution
time frame: Day 1
description: Volume of distribution in the terminal elimination phase
measure: Pharmacodynamics-Whole Blood Ex Vivo Stimulation
time frame: Day 1
description: Analysis of peripheral blood cell proliferation
measure: Pharmacodynamic - Bone Marrow Analysis
time frame: Day 1
description: Analysis of hematopoietic stem and progenitor cell (HSPC)
arm group label: Cohort 1
arm group type: Experimental
description: 6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion
arm group label: Cohort 2
arm group type: Experimental
description: Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 1; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
arm group label: Cohort 3
arm group type: Experimental
description: Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 2; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
arm group label: Cohort 4
arm group type: Experimental
description: Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 3; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
arm group label: Cohort 5
arm group type: Experimental
description: Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 4; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
arm group label: Cohort 6
arm group type: Experimental
description: Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 5; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
arm group label: Cohort 7 - Bone Marrow Cohort
arm group type: Experimental
description: All subjects in this cohort will receive active drug, G1T28-1. Dose of G1T28-1 will be determined based on the safety and PK data from previous cohorts. G1T28-1 will be administered in 50mL of 5% dextrose by IV infusion. Subjects in this cohort will be selected for the Ex-Vivo Stimulation group and will have a one time bone marrow aspirate at one of the following time points: pre dose, 12 or 24 hours post dose.
intervention type: Drug
intervention name: G1T28-1 (CDK 4/6 Inhibitor)
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
arm group label: Cohort 5
arm group label: Cohort 6
arm group label: Cohort 7 - Bone Marrow Cohort
intervention type: Drug
intervention name: Placebo
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
arm group label: Cohort 5
arm group label: Cohort 6
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Renger Tiessen, MD
role: Principal Investigator
affiliation: PRA Clinic Netherlands
facility: 
country: Netherlands
responsible party type: Sponsor