<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/NCT01695954</url>
  </required_header>
  <id_info>
    <org_study_id>11-01787</org_study_id>
    <nct_id>NCT01695954</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz</brief_title>
  <official_title>The Effect of Efavirenz and Ritonavir-boosted Darunavir on the Pharmacokinetics of the HMG CoA Reductase Inhibitor Pitavastatin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>New York City Health and Hospitals Corporation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kowa Pharmaceuticals America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University at Buffalo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main goal of this study is to determine how taking efavirenz affects the levels of&#xD;
      pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir&#xD;
      with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to&#xD;
      see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are&#xD;
      taken together and to see how taking pitavastatin affects the levels in the blood of&#xD;
      darunavir.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HIV infected persons are at risk for coronary heart disease due to chronic inflammation&#xD;
      associated with the virus itself, the side effects of the antiretroviral (ARV) therapies&#xD;
      which can cause elevated cholesterol, and the risk factors such as smoking, high blood&#xD;
      pressure and family history of heart disease.&#xD;
&#xD;
      The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the&#xD;
      protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol&#xD;
      in patients infected with HIV, guidelines recommend the use of statins (a class of lipid&#xD;
      lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the&#xD;
      levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food&#xD;
      and Drug Administration (FDA) for the treatment of high cholesterol.&#xD;
&#xD;
      In order to be able to use pitavastatin safely in HIV-infected patients taking either&#xD;
      darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with&#xD;
      darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these&#xD;
      drugs in the bloodstream.&#xD;
&#xD;
      Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in&#xD;
      Arm B.&#xD;
&#xD;
      Arm A:&#xD;
&#xD;
      Participants will start taking pitavastatin 2 mg tablets every night at bedtime. On day 4&#xD;
      participants will come in for a 14-hour pharmacokinetic (PK) overnight visit and will have&#xD;
      about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood&#xD;
      draw for a final blood draw. They will then stop taking pitavastatin. Participants will then&#xD;
      start taking one efavirenz 600 mg tablet at bedtime.&#xD;
&#xD;
      On day 14, participants will come in for a second 14-hour visit and will have about 9&#xD;
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final&#xD;
      blood draw. Participants will then start taking both pitavastatin and efavirenz at bedtime.&#xD;
&#xD;
      On day 18, participants will come in for a third 14-hour PK visit and will have about 9&#xD;
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final&#xD;
      blood draw. They will then stop taking all study drugs and will either come in or receive a&#xD;
      final phone call on day 25.&#xD;
&#xD;
      Arm B:&#xD;
&#xD;
      Participants will start taking one pitavastatin 2 mg tablet every morning. On day 4&#xD;
      participants will come in for a 14-hour pharmacokinetic (PK) daytime visit and will have&#xD;
      about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood&#xD;
      draw for a final blood draw. They will then stop taking pitavastatin. Participants will then&#xD;
      start taking darunavir 400 mg tablets (2) and ritonavir 100 mg tablets (1) every morning.&#xD;
&#xD;
      On day 14, participants will come in for a second 14-hour visit and will have about 9&#xD;
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final&#xD;
      blood draw. Participants will then start taking one pitavastatin 2mg tablet, two darunavir&#xD;
      400 mg tablets and one ritonavir 100 mg tablet.&#xD;
&#xD;
      On day 18, participants will come in for a third 14-hour PK visit and will have about 9&#xD;
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final&#xD;
      blood draw. They will then stop taking all study drugs and will either come in or receive a&#xD;
      final phone call on day 25.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">January 2013</completion_date>
  <primary_completion_date type="Actual">January 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>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>0 to 24 hours</time_frame>
    <description>24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin</measure>
    <time_frame>0 to 24 hours</time_frame>
    <description>Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir</measure>
    <time_frame>Day 18</time_frame>
    <description>Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Hyperlipidemia</condition>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pitavastatin</intervention_name>
    <description>Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Livalo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Darunavir</intervention_name>
    <description>Darunavir 400 mg tablets x 2 taken daily in Arm B</description>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Prezista</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <description>Ritonavir 100 mg tablets taken daily in Arm B</description>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Norvir</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Efavirenz</intervention_name>
    <description>Efavirenz 600 mg tablets taken at bedtime in Arm A</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>Sustiva</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Absence of HIV-1 infection as documented by any licensed ELISA test kit within 21 days&#xD;
             prior to study entry.&#xD;
&#xD;
          -  Male or female aged 18-60 years.&#xD;
&#xD;
          -  Able and willing to provide informed consent.&#xD;
&#xD;
          -  All men and women of reproductive potential must practice adequate birth control to&#xD;
             prevent pregnancy from start of the study until completion of the study.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             within 14 days prior to study entry and day of entry.&#xD;
&#xD;
          -  Hemoglobin &gt; 12.5 g/dL for men; &gt; 11.5 g/dL for women;&#xD;
&#xD;
          -  Absolute neutrophil count &gt;1,500 cells/mm3;&#xD;
&#xD;
          -  Platelet count &gt; 100,000 platelets/mm3;&#xD;
&#xD;
          -  AST (SGOT)/ALT (SGPT) &lt;1.5X ULN;&#xD;
&#xD;
          -  Creatinine &lt;1.5 X ULN&#xD;
&#xD;
          -  Subject is within 20% (+/-) of ideal body weight and must weigh at least 50 kg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of illicit drugs or alcohol which would interfere with the completion of this&#xD;
             study.&#xD;
&#xD;
          -  Pregnancy or breast-feeding.&#xD;
&#xD;
          -  History of chronic illnesses such as hypertension, coronary artery disease, arthritis,&#xD;
             diabetes, or any chronic gastrointestinal conditions which might interfere with drug&#xD;
             absorption.&#xD;
&#xD;
          -  Any medical condition which, in the opinion of the investigator, would interfere with&#xD;
             the subjects ability to participate in this protocol.&#xD;
&#xD;
          -  Use of prohibited protocol-specified drugs, prescription or over-the-counter within 14&#xD;
             days prior to study entry.&#xD;
&#xD;
          -  Participation in any investigational drug studies within 30 days prior to study entry.&#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>Judith Aberg, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bellevue/NYU AIDS Clinical Trials Unit</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Malvestutto CD, Ma Q, Morse GD, Underberg JA, Aberg JA. Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):390-6. doi: 10.1097/QAI.0000000000000333.</citation>
    <PMID>25202920</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>January 22, 2014</results_first_submitted>
  <results_first_submitted_qc>July 22, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 11, 2020</results_first_posted>
  <last_update_submitted>July 22, 2020</last_update_submitted>
  <last_update_submitted_qc>July 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>Hyperlipidemia</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Statins</keyword>
  <keyword>Darunavir</keyword>
  <keyword>Efavirenz</keyword>
  <keyword>Pitavastatin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipidemias</mesh_term>
    <mesh_term>Hyperlipoproteinemias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Darunavir</mesh_term>
    <mesh_term>Efavirenz</mesh_term>
    <mesh_term>Pitavastatin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Accrual began August 24, 2012 and ended January, 8, 2013. All study procedures took place at the NYU/Bellevue Clinical Trials Unit and NYU Clinical and Translational Science Institute.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm A: (Pitavastatin and Efavirenz)</title>
          <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.</description>
        </group>
        <group group_id="P2">
          <title>Arm B: (Pitavastatin and Ritonavir-boosted Darunavir)</title>
          <description>Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm A: (Pitavastatin and Efavirenz)</title>
          <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.</description>
        </group>
        <group group_id="B2">
          <title>Arm B: (Pitavastatin and Ritonavir-boosted Darunavir)</title>
          <description>Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC</title>
        <description>24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin</description>
        <time_frame>0 to 24 hours</time_frame>
        <population>Subjects who completed all visits</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: (Pitavastatin and Efavirenz)</title>
            <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime for the first 4 days, then efavirenz 600 mg at bedtime for the next 10 days and both pitavastatin 2 mg and efavirenz 600 mg at bedtime for the final 4 days. Blood will be drawn on days 0, 4, 14 and 18.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: (Pitavastatin and Darunavir)</title>
            <description>Subjects in arm will receive pitavastatin 2 mg daily for the first 4 days, then darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the next 10 days and will receive both pitavastatin 2 mg and darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the final 4 days. Blood will be drawn on days 0, 4, 14, and 18.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC</title>
          <description>24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin</description>
          <population>Subjects who completed all visits</population>
          <units>ng*hr/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.3" spread="5.72"/>
                    <measurement group_id="O2" value="62.8" spread="6.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir</title>
        <description>Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.</description>
        <time_frame>Day 18</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: (Pitavastatin and Efavirenz)</title>
            <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: (Pitavastatin and Ritonavir-boosted Darunavir)</title>
            <description>Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.</description>
          </group>
        </group_list>
        <measure>
          <title>GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir</title>
          <description>Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.</description>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.20" lower_limit="0.79" upper_limit="1.83"/>
                    <measurement group_id="O2" value="0.93" lower_limit="0.72" upper_limit="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin</title>
        <description>Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin</description>
        <time_frame>0 to 24 hours</time_frame>
        <population>Subjects who completed all visits</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: (Pitavastatin and Efavirenz)</title>
            <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime for the first 4 days, then efavirenz 600 mg at bedtime for the next 10 days and both pitavastatin 2 mg and efavirenz 600 mg at bedtime for the final 4 days. Blood will be drawn on days 0, 4, 14 and 18.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: (Pitavastatin and Darunavir)</title>
            <description>Subjects in arm will receive pitavastatin 2 mg daily for the first 4 days, then darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the next 10 days and will receive both pitavastatin 2 mg and darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the final 4 days. Blood will be drawn on days 0, 4, 14, and 18.</description>
          </group>
        </group_list>
        <measure>
          <title>GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin</title>
          <description>Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin</description>
          <population>Subjects who completed all visits</population>
          <units>Ratio</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>GMR of Pitavastatin with (EFV or DRV)/Pitavastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".89" lower_limit=".7321" upper_limit="1.09"/>
                    <measurement group_id="O2" value=".91" lower_limit=".78" upper_limit="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GMR of (EFV or DRV) with Pitavastatin/(EFV or DRV)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".90" lower_limit=".75" upper_limit="1.06"/>
                    <measurement group_id="O2" value="1.08" lower_limit=".96" upper_limit="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>7 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A: (Pitavastatin and Efavirenz)</title>
          <description>Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.</description>
        </group>
        <group group_id="E2">
          <title>Arm B: (Pitavastatin and Ritonavir-boosted Darunavir)</title>
          <description>Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="14" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>CPK elevation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain at venipuncture site</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vivid dreams</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </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="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </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>
    <limitations_and_caveats>Pitavastatin levels for 4 subjects enrolled in Arm B were lost due to emergency transfer of specimens to temporary storage facility during Hurricane Sandy.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Carlos Malvestutto, MD, MPH</name_or_title>
      <organization>NYU School of Medicine</organization>
      <phone>212-263-3570</phone>
      <email>carlos.malvestutto@nyumc.org</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/NCT01695954
org study id: 11-01787
nct id: NCT01695954
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The main goal of this study is to determine how taking efavirenz affects the levels of
      pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir
      with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to
      see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are
      taken together and to see how taking pitavastatin affects the levels in the blood of
      darunavir.
HIV infected persons are at risk for coronary heart disease due to chronic inflammation
      associated with the virus itself, the side effects of the antiretroviral (ARV) therapies
      which can cause elevated cholesterol, and the risk factors such as smoking, high blood
      pressure and family history of heart disease.

      The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the
      protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol
      in patients infected with HIV, guidelines recommend the use of statins (a class of lipid
      lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the
      levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food
      and Drug Administration (FDA) for the treatment of high cholesterol.

      In order to be able to use pitavastatin safely in HIV-infected patients taking either
      darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with
      darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these
      drugs in the bloodstream.

      Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in
      Arm B.

      Arm A:

      Participants will start taking pitavastatin 2 mg tablets every night at bedtime. On day 4
      participants will come in for a 14-hour pharmacokinetic (PK) overnight visit and will have
      about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood
      draw for a final blood draw. They will then stop taking pitavastatin. Participants will then
      start taking one efavirenz 600 mg tablet at bedtime.

      On day 14, participants will come in for a second 14-hour visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. Participants will then start taking both pitavastatin and efavirenz at bedtime.

      On day 18, participants will come in for a third 14-hour PK visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. They will then stop taking all study drugs and will either come in or receive a
      final phone call on day 25.

      Arm B:

      Participants will start taking one pitavastatin 2 mg tablet every morning. On day 4
      participants will come in for a 14-hour pharmacokinetic (PK) daytime visit and will have
      about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood
      draw for a final blood draw. They will then stop taking pitavastatin. Participants will then
      start taking darunavir 400 mg tablets (2) and ritonavir 100 mg tablets (1) every morning.

      On day 14, participants will come in for a second 14-hour visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. Participants will then start taking one pitavastatin 2mg tablet, two darunavir
      400 mg tablets and one ritonavir 100 mg tablet.

      On day 18, participants will come in for a third 14-hour PK visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. They will then stop taking all study drugs and will either come in or receive a
      final phone call on day 25.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC
time frame: 0 to 24 hours
description: 24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin
measure: GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin
time frame: 0 to 24 hours
description: Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin
measure: GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir
time frame: Day 18
description: Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.
arm group label: Arm A
arm group type: Experimental
description: Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.
arm group label: Arm B
arm group type: Experimental
description: Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
intervention type: Drug
intervention name: Pitavastatin
description: Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.
arm group label: Arm A
arm group label: Arm B
other name: Livalo
intervention type: Drug
intervention name: Darunavir
description: Darunavir 400 mg tablets x 2 taken daily in Arm B
arm group label: Arm B
other name: Prezista
intervention type: Drug
intervention name: Ritonavir
description: Ritonavir 100 mg tablets taken daily in Arm B
arm group label: Arm B
other name: Norvir
intervention type: Drug
intervention name: Efavirenz
description: Efavirenz 600 mg tablets taken at bedtime in Arm A
arm group label: Arm A
other name: Sustiva
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Judith Aberg, M.D.
role: Principal Investigator
affiliation: NYU School of Medicine
facility: 
country: United States
citation: Malvestutto CD, Ma Q, Morse GD, Underberg JA, Aberg JA. Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):390-6. doi: 10.1097/QAI.0000000000000333.
PMID: 25202920
responsible party type: Sponsor
mesh term: Hyperlipidemias
mesh term: Hyperlipoproteinemias
mesh term: Ritonavir
mesh term: Darunavir
mesh term: Efavirenz
mesh term: Pitavastatin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Pitavastatin levels for 4 subjects enrolled in Arm B were lost due to emergency transfer of specimens to temporary storage facility during Hurricane Sandy.
point of contact: 