<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/NCT01712828</url>
  </required_header>
  <id_info>
    <org_study_id>CC-5013-CP-011</org_study_id>
    <nct_id>NCT01712828</nct_id>
  </id_info>
  <brief_title>Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Males</brief_title>
  <official_title>A Phase 1, Open-Label, Two-Part, Fixed-Sequence Crossover Study to Evaluate the Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Covance</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To find out if the blood level of lenalidomide can be changed when a drug that prevents&#xD;
      p-glycoprotein (a protein naturally present in the body that helps carry substances across&#xD;
      cell membranes that is found in many parts of the body like the intestines, liver, and&#xD;
      kidneys) from working (called a P-gp inhibitor) when taken together with lenalidomide. The&#xD;
      study is also trying to find out if blood level of temsirolimus can be changed when a subject&#xD;
      takes lenalidomide together with temsirolimus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a single-center, open label, 2-part study. Part 1 will be a two-period,&#xD;
      fixed-sequence crossover study with lenalidomide alone in Period 1, followed by lenalidomide&#xD;
      in combination with quinidine in Period 2. Part 2 will be a fixed-sequence, three-period,&#xD;
      crossover study with lenalidomide alone in Period 1, temsirolimus (via direct intravenous&#xD;
      infusion) in Period 2, and lenalidomide in combination with temsirolimus (via direct&#xD;
      intravenous infusion) in Period 3. Diphenhydramine (given via intravenous injection) will be&#xD;
      administered shortly before temsirolimus in order to decrease the chances of an allergic&#xD;
      reaction to temsirolimus. Part 1 and Part 2 will be conducted at the same time. Subjects can&#xD;
      only participate in either Part 1 or Part 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2012</start_date>
  <completion_date type="Actual">January 1, 2013</completion_date>
  <primary_completion_date type="Actual">January 1, 2013</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lenalidomide PK-AUC (0-24)</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to 24 hours post dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lenalidomide PK-(Cmax)</measure>
    <time_frame>Up to 21 days (including washout phase)</time_frame>
    <description>Maximum observed plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lenalidomide PK-(Tmax)</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Time to maximum observed plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lenalidomide PK-AUC(0-t)</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lenalidomide PK-AUC(0-∞)</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero extrapolated to infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lenalidomide PK-(T1/2)</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Estimate of the terminal elimination half-life in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Temsirolimus and Sirolimus PK-AUC (0-24)</measure>
    <time_frame>Up to 38 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to 24 hours post dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Temsirolimus and Sirolimus PK-(Cmax)</measure>
    <time_frame>Up to 38 days</time_frame>
    <description>Maximum observed plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Temsirolimus and Sirolimus PK-(Tmax)</measure>
    <time_frame>Up to 38 days</time_frame>
    <description>Time to maximum observed plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Temsirolimus and Sirolimus PK-(AUC 0-t)</measure>
    <time_frame>Up to 38 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>Safety monitoring will be done by regular adverse event assessment, concomitant medication, clinical laboratory tests, physical exams, ECGs, and vital signs.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Lenalidomide plus Quinidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Lenalidomide plusTemsirolimus and Diphenhydramine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period</description>
    <arm_group_label>Lenalidomide plus Quinidine</arm_group_label>
    <arm_group_label>Lenalidomide plusTemsirolimus and Diphenhydramine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quinidine</intervention_name>
    <description>300 mg of Quinidine will be administered orally every 12 hours for 1 day followed by 600 mg of Quinidine administered orally every 12 hours for the next 4 consecutive days</description>
    <arm_group_label>Lenalidomide plus Quinidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temsirolimus</intervention_name>
    <description>25 mg/mL injection of Temsirolimus will be given directly into the vein over 30 minutes once in the second period and once with Lenalidomide in the third period.</description>
    <arm_group_label>Lenalidomide plusTemsirolimus and Diphenhydramine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diphenhydramine</intervention_name>
    <description>Just before Temsirolimus is given, 25 mg of Diphenhydramine (Benadryl) will be given directly into the vein to decrease chances of an allergic reaction to Temsirolimus.</description>
    <arm_group_label>Lenalidomide plusTemsirolimus and Diphenhydramine</arm_group_label>
    <other_name>Benadryl</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must understand and voluntarily sign a written informed consent form prior to any&#xD;
             study-related procedures being performed.&#xD;
&#xD;
          -  Must be able to communicate with the investigator, understand and comply with the&#xD;
             requirements of the study, and agree to adhere to restrictions and examination&#xD;
             schedules.&#xD;
&#xD;
          -  Healthy male volunteer of any race between 18 to 65 years of age (inclusive), and in&#xD;
             good health as determined by a physical exam.&#xD;
&#xD;
          -  Agree to use barrier contraception (i.e., condoms not made of natural (animal)&#xD;
             membrane [e.g., latex or polyurethane condoms are acceptable]) when engaging in sexual&#xD;
             activity with a female of child-bearing potential while on study drug, and for at&#xD;
             least 90 days after the last dose of study drug.&#xD;
&#xD;
          -  Must have a body mass index between 18 and 33 kg/m2 (inclusive).&#xD;
&#xD;
          -  Clinical laboratory tests must be within normal limits or acceptable to the principal&#xD;
             investigator.&#xD;
&#xD;
          -  Must have confirmation of normal renal function (defined as an estimate glomerular&#xD;
             filtration rate &gt;90 mL/min).&#xD;
&#xD;
          -  Must be afebrile, with supine systolic blood pressure: 90 to 140 mmHg, supine&#xD;
             diastolic blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm.&#xD;
&#xD;
          -  Must have a normal or clinically acceptable 12-lead electrocardiogram, with a QTcF&#xD;
             (Fridericia's correction formula) value ≤ 430 msec.&#xD;
&#xD;
          -  Must refrain from sperm donations for the entire duration of the study, and for at&#xD;
             least 90 days after the last dose of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any clinically significant and relevant neurological, gastrointestinal,&#xD;
             renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine,&#xD;
             hematological, allergic disease, drug allergies, known hypersensitivity to a member of&#xD;
             the class of immunomodulatory drugs (IMiDs®), temosirolimus, sirolimus, polysorbate&#xD;
             80, diphenhydramine, or to any other component (or excipients) of Torisel®, or other&#xD;
             major disorders.&#xD;
&#xD;
          -  Any condition which places the subject at unacceptable risk if he were to participate&#xD;
             in the study, or confounds the ability to interpret data from the study.&#xD;
&#xD;
          -  Used any prescribed systemic or topical medication within 30 days of the first dose&#xD;
             administration, unless Sponsor agreement is obtained.&#xD;
&#xD;
          -  Used any non-prescribed systemic or topical medication (including vitamin/mineral&#xD;
             supplements, and herbal medicines) within 14 days of the first dose administration,&#xD;
             unless Sponsor agreement is obtained.&#xD;
&#xD;
          -  Used any prescribed, or non-prescribed, systemic or topical medication that is a CYP3A&#xD;
             inhibitor or inducer within 30 days of first dose administration. (refer to&#xD;
             (http://medicine.iupui.edu/clinpharm/ddis/p450_Table_Oct_11_2009.pdf)&#xD;
&#xD;
          -  Has any surgical or medical conditions (excluding appendectomy) possibly affecting&#xD;
             drug absorption, distribution, metabolism and excretion, e.g., bariatric procedure.&#xD;
&#xD;
          -  Donated blood or plasma within 8 weeks before the first dose administration to a blood&#xD;
             bank or blood donation center.&#xD;
&#xD;
          -  History of drug abuse (as defined by the current version of the Diagnostic and&#xD;
             Statistical Manual within 2 years before dosing, or positive drug screening test&#xD;
             reflecting consumption of illicit drugs.&#xD;
&#xD;
          -  History of alcohol abuse (as defined by the current version of the Diagnostic and&#xD;
             Statistical Manual) within 2 years before dosing, or positive alcohol screen.&#xD;
&#xD;
          -  Known to have serum hepatitis or known to be a carrier of the hepatitis B surface&#xD;
             antigen (HBsAg), or hepatitis C antibody (HCVAb), or have a positive result to the&#xD;
             test for HIV antibodies at Screening.&#xD;
&#xD;
          -  Exposed to an investigational drug (new chemical entity) within 30 days preceding the&#xD;
             first dose administration, or 5 half-lives of that investigational drug, if known&#xD;
             (whichever is longer).&#xD;
&#xD;
          -  For Part 2 only: has total bilirubin ≥ 1.5x upper limit of normal&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>Edward O'Mara, MD</last_name>
    <role>Study Director</role>
    <affiliation>Celgene Corporation</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>
  <link>
    <url>http://us.testwiththebest.com/find-our--clinics/our-dallas-clinic.html</url>
    <description>Related Info</description>
  </link>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <last_update_submitted>November 6, 2019</last_update_submitted>
  <last_update_submitted_qc>November 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lenalidomide,</keyword>
  <keyword>Revlimid,</keyword>
  <keyword>pharmacokinetics,</keyword>
  <keyword>healthy male subjects</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diphenhydramine</mesh_term>
    <mesh_term>Promethazine</mesh_term>
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Quinidine</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Temsirolimus</mesh_term>
    <mesh_term>MTOR Inhibitors</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/NCT01712828
org study id: CC-5013-CP-011
nct id: NCT01712828
lead sponsor: 
collaborator: 
has dmc: No
To find out if the blood level of lenalidomide can be changed when a drug that prevents
      p-glycoprotein (a protein naturally present in the body that helps carry substances across
      cell membranes that is found in many parts of the body like the intestines, liver, and
      kidneys) from working (called a P-gp inhibitor) when taken together with lenalidomide. The
      study is also trying to find out if blood level of temsirolimus can be changed when a subject
      takes lenalidomide together with temsirolimus.
This will be a single-center, open label, 2-part study. Part 1 will be a two-period,
      fixed-sequence crossover study with lenalidomide alone in Period 1, followed by lenalidomide
      in combination with quinidine in Period 2. Part 2 will be a fixed-sequence, three-period,
      crossover study with lenalidomide alone in Period 1, temsirolimus (via direct intravenous
      infusion) in Period 2, and lenalidomide in combination with temsirolimus (via direct
      intravenous infusion) in Period 3. Diphenhydramine (given via intravenous injection) will be
      administered shortly before temsirolimus in order to decrease the chances of an allergic
      reaction to temsirolimus. Part 1 and Part 2 will be conducted at the same time. Subjects can
      only participate in either Part 1 or Part 2.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Lenalidomide PK-AUC (0-24)
time frame: Up to 21 days
description: Area under the plasma concentration-time curve from time zero to 24 hours post dose
measure: Lenalidomide PK-(Cmax)
time frame: Up to 21 days (including washout phase)
description: Maximum observed plasma concentration
measure: Lenalidomide PK-(Tmax)
time frame: Up to 21 days
description: Time to maximum observed plasma concentration
measure: Lenalidomide PK-AUC(0-t)
time frame: Up to 21 days
description: Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point
measure: Lenalidomide PK-AUC(0-∞)
time frame: Up to 21 days
description: Area under the plasma concentration-time curve from time zero extrapolated to infinity
measure: Lenalidomide PK-(T1/2)
time frame: Up to 21 days
description: Estimate of the terminal elimination half-life in plasma
measure: Temsirolimus and Sirolimus PK-AUC (0-24)
time frame: Up to 38 days
description: Area under the plasma concentration-time curve from time zero to 24 hours post dose
measure: Temsirolimus and Sirolimus PK-(Cmax)
time frame: Up to 38 days
description: Maximum observed plasma concentration
measure: Temsirolimus and Sirolimus PK-(Tmax)
time frame: Up to 38 days
description: Time to maximum observed plasma concentration
measure: Temsirolimus and Sirolimus PK-(AUC 0-t)
time frame: Up to 38 days
description: Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point
measure: Number of participants with adverse events
time frame: Up to 6 weeks
description: Safety monitoring will be done by regular adverse event assessment, concomitant medication, clinical laboratory tests, physical exams, ECGs, and vital signs.
arm group label: Lenalidomide plus Quinidine
arm group type: Experimental
arm group label: Lenalidomide plusTemsirolimus and Diphenhydramine
arm group type: Experimental
intervention type: Drug
intervention name: Lenalidomide
description: 25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period
arm group label: Lenalidomide plus Quinidine
arm group label: Lenalidomide plusTemsirolimus and Diphenhydramine
intervention type: Drug
intervention name: Quinidine
description: 300 mg of Quinidine will be administered orally every 12 hours for 1 day followed by 600 mg of Quinidine administered orally every 12 hours for the next 4 consecutive days
arm group label: Lenalidomide plus Quinidine
intervention type: Drug
intervention name: Temsirolimus
description: 25 mg/mL injection of Temsirolimus will be given directly into the vein over 30 minutes once in the second period and once with Lenalidomide in the third period.
arm group label: Lenalidomide plusTemsirolimus and Diphenhydramine
intervention type: Drug
intervention name: Diphenhydramine
description: Just before Temsirolimus is given, 25 mg of Diphenhydramine (Benadryl) will be given directly into the vein to decrease chances of an allergic reaction to Temsirolimus.
arm group label: Lenalidomide plusTemsirolimus and Diphenhydramine
other name: Benadryl
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Edward O'Mara, MD
role: Study Director
affiliation: Celgene Corporation
facility: 
country: United States
url: http://us.testwiththebest.com/find-our--clinics/our-dallas-clinic.html
description: Related Info
responsible party type: Sponsor
mesh term: Diphenhydramine
mesh term: Promethazine
mesh term: Sirolimus
mesh term: Quinidine
mesh term: Lenalidomide
mesh term: Temsirolimus
mesh term: MTOR Inhibitors