<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/NCT01668147</url>
  </required_header>
  <id_info>
    <org_study_id>201205135</org_study_id>
    <nct_id>NCT01668147</nct_id>
  </id_info>
  <brief_title>Efavirenz and Ritonavir on Human Brain P-Glycoprotein</brief_title>
  <official_title>Influence of Efavirenz and Ritonavir on Human Brain P-Glycoprotein Activity Using PET Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine the effects of ritonavir and efavirenz on the activity of P-glycoprotein in&#xD;
      human brain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sequential crossover using tracer 11C-desmethylloperamide, a substrate for brain&#xD;
      P-glycoprotein, and positron emission tomography (PET), administered after nothing (control),&#xD;
      oral ritonavir (3d), and oral efavirenz (14d) with washout in between&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral [11C]dLop Distribution Volume</measure>
    <time_frame>1 day</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Drug Effects</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral ritonavir</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral efavirenz</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[11C] desmethyl-loperamide</intervention_name>
    <description>IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Oral efavirenz</arm_group_label>
    <arm_group_label>Oral ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control - no pretreatment</intervention_name>
    <description>Session 1: IV administration of 10-14 mCi [11C] desmethyl-loperamide (dLop) with PET/CT imaging and brain MRI</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral ritonavir</intervention_name>
    <description>Session 2: Pretreatment with oral ritonavir for 3 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI</description>
    <arm_group_label>Oral ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral efavirenz</intervention_name>
    <description>Session 3: Pretreatment with oral efavirenz for 14 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI</description>
    <arm_group_label>Oral efavirenz</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or non-pregnant female, 18-40 yr old&#xD;
&#xD;
          -  Good general health with no remarkable medical conditions&#xD;
&#xD;
          -  BMI &lt; 33&#xD;
&#xD;
          -  Provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known history of liver or kidney disease&#xD;
&#xD;
          -  History of major medical conditions&#xD;
&#xD;
          -  HIV seropositive&#xD;
&#xD;
          -  Fasting blood glucose &gt; 110 mg/dl&#xD;
&#xD;
          -  Family history of type 2 diabetes&#xD;
&#xD;
          -  Use of prescription or non prescription medications, herbals or foods known to be&#xD;
             metabolized by or altering P-glycoprotein or CYP3A activity (hormonal birth control&#xD;
             medications are acceptable if alternative means of contraception are used)&#xD;
&#xD;
          -  Females who are pregnant or nursing&#xD;
&#xD;
          -  Females taking hormonal contraceptives who are unwilling to use alternative means of&#xD;
             contraception&#xD;
&#xD;
          -  Contraindications to MRI&#xD;
&#xD;
          -  Contraindications to PET scanning&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Evan Kharasch, MD, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>June 21, 2018</results_first_submitted>
  <results_first_submitted_qc>January 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 22, 2020</results_first_posted>
  <last_update_submitted>January 8, 2020</last_update_submitted>
  <last_update_submitted_qc>January 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PET Imaging</keyword>
  <keyword>Efavirenz</keyword>
  <keyword>Ritonavir</keyword>
  <keyword>[11C] desmethyl-loperamide</keyword>
  <keyword>Healthy volunteers</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Efavirenz</mesh_term>
    <mesh_term>Loperamide</mesh_term>
    <mesh_term>Antidiarrheals</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>PET/CT Imaging</title>
          <description>Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Study Arm</title>
          <description>Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27" spread="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cerebral [11C]dLop Distribution Volume</title>
        <time_frame>1 day</time_frame>
        <population>0 Participants Analyzed/Assigned. The PI has left the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.</population>
        <group_list>
          <group group_id="O1">
            <title>Control (no Pretreatment)</title>
            <description>Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
          </group>
          <group group_id="O2">
            <title>Oral Ritonavir</title>
            <description>Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
          </group>
          <group group_id="O3">
            <title>Oral Efavirenz</title>
            <description>Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
          </group>
        </group_list>
        <measure>
          <title>Cerebral [11C]dLop Distribution Volume</title>
          <population>0 Participants Analyzed/Assigned. The PI has left the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Control (no Pretreatment)</title>
          <description>Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
        </group>
        <group group_id="E2">
          <title>Oral Ritonvir</title>
          <description>Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
        </group>
        <group group_id="E3">
          <title>Oral Efavirenz</title>
          <description>Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging&#xD;
[11C] desmethyl-loperamide: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging after control, ritonavir or efavirenz</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Evan Kharasch MD PhD</name_or_title>
      <organization>Washington University</organization>
      <phone>3143628796</phone>
      <email>kharasch@wustl.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01668147
org study id: 201205135
nct id: NCT01668147
lead sponsor: 
has dmc: No
To determine the effects of ritonavir and efavirenz on the activity of P-glycoprotein in
      human brain.
Sequential crossover using tracer 11C-desmethylloperamide, a substrate for brain
      P-glycoprotein, and positron emission tomography (PET), administered after nothing (control),
      oral ritonavir (3d), and oral efavirenz (14d) with washout in between
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Other
masking: None (Open Label)
measure: Cerebral [11C]dLop Distribution Volume
time frame: 1 day
arm group label: Control
arm group type: Experimental
description: Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging
arm group label: Oral ritonavir
arm group type: Active Comparator
description: Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging
arm group label: Oral efavirenz
arm group type: Active Comparator
description: Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging
intervention type: Drug
intervention name: [11C] desmethyl-loperamide
description: IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging
arm group label: Control
arm group label: Oral efavirenz
arm group label: Oral ritonavir
intervention type: Other
intervention name: Control - no pretreatment
description: Session 1: IV administration of 10-14 mCi [11C] desmethyl-loperamide (dLop) with PET/CT imaging and brain MRI
arm group label: Control
intervention type: Drug
intervention name: Oral ritonavir
description: Session 2: Pretreatment with oral ritonavir for 3 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI
arm group label: Oral ritonavir
intervention type: Drug
intervention name: Oral efavirenz
description: Session 3: Pretreatment with oral efavirenz for 14 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI
arm group label: Oral efavirenz
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Evan Kharasch, MD, PhD.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ritonavir
mesh term: Efavirenz
mesh term: Loperamide
mesh term: Antidiarrheals
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 