<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/NCT02222441</url>
  </required_header>
  <id_info>
    <org_study_id>A5481039</org_study_id>
    <nct_id>NCT02222441</nct_id>
  </id_info>
  <brief_title>Effect Of Modafinil And Pioglitazone On The Pharmacokinetics Of Palbociclib (PD-0332991)</brief_title>
  <official_title>A Phase 1, Open-label, Fixed-sequence, 2-cohort, 2-period Study To Investigate The Effect Of Modafinil And Pioglitazone Given As Multiple Doses On Single Dose Pharmacokinetics Of Palbociclib (Pd-0332991) In Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to evaluate the potential effect of the moderate CYP3A inducer&#xD;
      modafinil and the weak CYP3A inducer pioglitazone on the pharmacokinetics of palbociclib.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]</measure>
    <time_frame>0-120 hours</time_frame>
    <description>AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>0-120 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma Palbociclib Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)</measure>
    <time_frame>0 to 120 hours</time_frame>
    <description>Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Palbociclib Time to Reach Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>0 to 120 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Palbociclib Decay Half-Life (t1/2)</measure>
    <time_frame>0 to 120 hours</time_frame>
    <description>Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Oral Clearance (CL/F) of Palbociclib</measure>
    <time_frame>0 to 120 hours</time_frame>
    <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/F) of Palbociclib</measure>
    <time_frame>0 to 120 hours</time_frame>
    <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Plasma Concentrations of Modafinil, Modafinil sulfone, pioglitazone, hydroxy derivative of pioglitazone, and keto derivative of pioglitazone</measure>
    <time_frame>0 to 120 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of last quantifiable concentration for palbociclib</measure>
    <time_frame>0 to 120 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Fixed sequence modafinil DDI arm (Cohort 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fixed sequence study with treatment A of palbociclib alone, followed by treatment B of palbociclib with modafinil in Cohort 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fixed sequence pioglitazone DDI arm (Cohort 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For Cohort 2, fixed sequence study with treatment A of palbociclib alone, followed by treatment C of palbociclib with pioglitazone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib alone</intervention_name>
    <description>A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection.</description>
    <arm_group_label>Fixed sequence modafinil DDI arm (Cohort 1)</arm_group_label>
    <other_name>Palbociclib, PD-0332991</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib plus Modafinil</intervention_name>
    <description>For Cohort 1, modafinil 200 mg once daily for 7 days, followed by 400 mg once daily for 25 days; on Day 28, a single oral 125 mg dose of palbociclib will be given with modafinil after a meal, followed by 120 hours of PK sample collection.</description>
    <arm_group_label>Fixed sequence modafinil DDI arm (Cohort 1)</arm_group_label>
    <other_name>Palbociclib (PD-0332991); Modafinil (Provigil)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib alone</intervention_name>
    <description>A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection.</description>
    <arm_group_label>Fixed sequence pioglitazone DDI arm (Cohort 2)</arm_group_label>
    <other_name>Palbociclib, PD-0332991</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib plus pioglitazone</intervention_name>
    <description>For Cohort 2, pioglitazone 45 mg once daily for a total of 19 days; On Day 15, a single oral 125 mg dose of palbociclib will be given with pioglitazone after a meal, followed by 120 hours of PK sample collection.</description>
    <arm_group_label>Fixed sequence pioglitazone DDI arm (Cohort 2)</arm_group_label>
    <other_name>Palbociclib (PD-0332991); Pioglitazone (Actos)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and/or female subjects of non childbearing potential between the ages of&#xD;
             18 and 55 years, inclusive.&#xD;
&#xD;
          -  Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight &gt;50 kg (110 lbs).&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          -  Subjects who are willing and able to comply with all scheduled visits, treatment plan,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or&#xD;
             allergic disease.&#xD;
&#xD;
          -  Any condition possibly affecting drug absorption (eg, gastrectomy).&#xD;
&#xD;
          -  Subjects with a self-reported history of addiction, especially to stimulants.&#xD;
&#xD;
          -  A positive urine drug screen or alcohol breath test.&#xD;
&#xD;
          -  Pregnant female subjects; breastfeeding female subjects; female subjects of&#xD;
             childbearing potential; male subjects with partners currently pregnant; male subjects&#xD;
             of childbearing potential who are unwilling or unable to use a highly effective method&#xD;
             of contraception as outlined in this protocol for the duration of the study and for 90&#xD;
             days after the last dose of investigational product.&#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>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New Haven Clinical Research Unit</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A5481039&amp;StudyName=Effect%20Of%20Modafinil%20And%20Pioglitazone%20On%20The%20Pharmacokinetics%20Of%20Palbociclib%20%28PD-0332991%29</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <last_update_submitted>February 18, 2015</last_update_submitted>
  <last_update_submitted_qc>February 18, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 20, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Palbociclib</keyword>
  <keyword>Modafinil</keyword>
  <keyword>Pioglitazone</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Drug-Drug Interaction Study</keyword>
  <keyword>Healthy Volunteers</keyword>
  <keyword>CYP3A Inducers</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pioglitazone</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
    <mesh_term>Modafinil</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/NCT02222441
org study id: A5481039
nct id: NCT02222441
lead sponsor: 
has dmc: No
This study is designed to evaluate the potential effect of the moderate CYP3A inducer
      modafinil and the weak CYP3A inducer pioglitazone on the pharmacokinetics of palbociclib.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
time frame: 0-120 hours
description: AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: 0-120 hours
measure: Plasma Palbociclib Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
time frame: 0 to 120 hours
description: Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
measure: Plasma Palbociclib Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: 0 to 120 hours
measure: Plasma Palbociclib Decay Half-Life (t1/2)
time frame: 0 to 120 hours
description: Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
measure: Apparent Oral Clearance (CL/F) of Palbociclib
time frame: 0 to 120 hours
description: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
measure: Apparent Volume of Distribution (Vz/F) of Palbociclib
time frame: 0 to 120 hours
description: Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
measure: Trough Plasma Concentrations of Modafinil, Modafinil sulfone, pioglitazone, hydroxy derivative of pioglitazone, and keto derivative of pioglitazone
time frame: 0 to 120 hours
measure: Time of last quantifiable concentration for palbociclib
time frame: 0 to 120 hours
arm group label: Fixed sequence modafinil DDI arm (Cohort 1)
arm group type: Experimental
description: Fixed sequence study with treatment A of palbociclib alone, followed by treatment B of palbociclib with modafinil in Cohort 1.
arm group label: Fixed sequence pioglitazone DDI arm (Cohort 2)
arm group type: Experimental
description: For Cohort 2, fixed sequence study with treatment A of palbociclib alone, followed by treatment C of palbociclib with pioglitazone.
intervention type: Drug
intervention name: Palbociclib alone
description: A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection.
arm group label: Fixed sequence modafinil DDI arm (Cohort 1)
other name: Palbociclib, PD-0332991
intervention type: Drug
intervention name: Palbociclib plus Modafinil
description: For Cohort 1, modafinil 200 mg once daily for 7 days, followed by 400 mg once daily for 25 days; on Day 28, a single oral 125 mg dose of palbociclib will be given with modafinil after a meal, followed by 120 hours of PK sample collection.
arm group label: Fixed sequence modafinil DDI arm (Cohort 1)
other name: Palbociclib (PD-0332991); Modafinil (Provigil)
intervention type: Drug
intervention name: Palbociclib alone
description: A single 125 mg dose of palbociclib free base capsule given orally alone in the fed state, followed by 120 hours of PK sample collection.
arm group label: Fixed sequence pioglitazone DDI arm (Cohort 2)
other name: Palbociclib, PD-0332991
intervention type: Drug
intervention name: Palbociclib plus pioglitazone
description: For Cohort 2, pioglitazone 45 mg once daily for a total of 19 days; On Day 15, a single oral 125 mg dose of palbociclib will be given with pioglitazone after a meal, followed by 120 hours of PK sample collection.
arm group label: Fixed sequence pioglitazone DDI arm (Cohort 2)
other name: Palbociclib (PD-0332991); Pioglitazone (Actos)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: United States
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A5481039&StudyName=Effect%20Of%20Modafinil%20And%20Pioglitazone%20On%20The%20Pharmacokinetics%20Of%20Palbociclib%20%28PD-0332991%29
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Pioglitazone
mesh term: Palbociclib
mesh term: Modafinil