<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/NCT01667978</url>
  </required_header>
  <id_info>
    <org_study_id>HS-12-00005</org_study_id>
    <nct_id>NCT01667978</nct_id>
  </id_info>
  <brief_title>The Effect of Protease Inhibitors on the Pharmacokinetics of Oral Norethindrone Contraception</brief_title>
  <acronym>NET</acronym>
  <official_title>The Effect of Protease Inhibitors on the Pharmacokinetics of Oral Norethindrone Contraception</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Society of Family Planning</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to learn if women taking the atazanavir and ritonavir have lower&#xD;
      levels of a birth control medication called norethindrone. Norethindrone (also called the&#xD;
      mini pill) is an FDA (Food and Drug Administration) approved progestin-only birth control&#xD;
      pill used to prevent pregnancy. Norethindrone is the standard medication used in women who&#xD;
      take the progestin only pill to prevent pregnancy. There are other birth control pills which&#xD;
      contain different medications. The investigators want to learn if HIV medications (atazanavir&#xD;
      and ritonavir) make the blood level of this birth control pill higher or lower. If the levels&#xD;
      of norethindrone are too low it may not work to prevent pregnancy. The investigators also&#xD;
      hope to learn about changes in the vaginal fluids and cervical fluids when women are taking&#xD;
      this birth control pill.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND/RATIONALE : It is recognized that there is a dearth of clinically applied,&#xD;
      population based, empiric data to guide contraceptive recommendations in HIV + women on&#xD;
      ARVs.(1) Protease inhibitors (PI) and non nucleoside reverse transcriptase inhibitors (NNRTI&#xD;
      ) induce micro enzyme systems such as CYP 3a4, which in turn alters the bio-availability and&#xD;
      pharmacokinetics of other concurrently administered medications.(2) Empiric trials from small&#xD;
      samples, often of 10-20 HIV negative subjects, have demonstrated that concurrent&#xD;
      administration of combined oral contraceptives (COC) and a PI or a NNRTI have been associated&#xD;
      with decreased plasma ethinyl estradiol (EE) levels. These pharmacokinetic findings have&#xD;
      raised concern that decreased bio-availability of EE may result in decreased contraceptive&#xD;
      efficacy, with possible increased unintended pregnancy. Some of these COC studies have&#xD;
      demonstrated that there is no change in the serum levels of norethindrone (NET) on&#xD;
      ARVs.(3-16) However, there are no published trials focused on oral NET or oral progestin-only&#xD;
      pills (POP) to guide management in HIV+ women.(17)&#xD;
&#xD;
      OBJECTIVES:&#xD;
&#xD;
      Primary objective of this study is:&#xD;
&#xD;
      To detect a ±40% difference in AUC of serum NET in HIV+ women taking ATV/RTV as compared to&#xD;
      AUC of NET in HIV+ women taking an ARV regimen that has demonstrated no interaction with NET&#xD;
      in the past.&#xD;
&#xD;
      Primary endpoint: Natural log-transformed NET PK parameter AUC from 0 to 72 hours following&#xD;
      oral administration, with multiple discrete serum data points for each subject on ATV/RTV.&#xD;
      This will be compared to natural log-transformed NET PK AUC from 0 to 72 hours following oral&#xD;
      administration, with multiple discrete serum data points for controls HIV+ women taking an&#xD;
      ARV regimen that has demonstrated no interaction with NET in the past.&#xD;
&#xD;
      The secondary objectives of this study are:&#xD;
&#xD;
      To evaluate the effect of ATV/RTV on other PK exposure endpoints and parameters of NET (with&#xD;
      natural log transformation). The sample and control groups mentioned above will again be&#xD;
      compared. Endpoints include:&#xD;
&#xD;
      minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), time to Cmax&#xD;
      (Tmax), and half-life (T1/2).&#xD;
&#xD;
      SAMPLE SIZE: Recruitment of 16 participants in each arm, with the goal of attaining 32&#xD;
      evaluable HIV-1-seropositive female subjects in total.&#xD;
&#xD;
      POPULATION/STUDY ARMS: HIV-1-infected female subjects 18-44 years of age&#xD;
&#xD;
      METHODOLOGY/INTERVENTIONS/FOLLOW-UP: A two-arm, open-label, prospective, steady state trial&#xD;
      to characterize the pharmacokinetics (PK) of oral norethindrone (NET) as a progestin only&#xD;
      contraceptive pill (POP) in HIV+ women receiving atazanavir and ritonavir therapy (ATV/RTV).&#xD;
      The investigators will identify a control group of HIV+ women who are taking ARV regimens&#xD;
      that have not significantly altered oral NET levels in prior trials. Subjects will be&#xD;
      enrolled in the trial for approximately 4 weeks A 28 day continuous packet of NET 0.35 mg&#xD;
      will be provided to all enrolled volunteers for 21 days of continuous administration. Women&#xD;
      who participate in this study will demonstrate a means of continuing their ARV regimens for&#xD;
      the duration of the study, ARV therapy will not be provided by this study. On day 22 subjects&#xD;
      will be admitted for serial pharmacokinetic (PK) specimens collection following the final&#xD;
      study dose of NET.&#xD;
&#xD;
      Subjects will be enrolled into one of the 2 arms based on their current ARV regimen.&#xD;
&#xD;
      Study group: Women on stable ARV/RTV (300/100mg daily) with additional ARV regimens that have&#xD;
      not significantly altered oral NET levels in prior trials. (n=12).&#xD;
&#xD;
      Control group: Stable on current ARV, no protease inhibitors (PI), ARV regimens that have not&#xD;
      significantly altered oral NET levels in previous research.&#xD;
&#xD;
      OUTCOMES: Intensive PK sampling for NET will be performed in those in intervention and&#xD;
      control arms after 21 days of NET administration. To determine side effect profile of NET by&#xD;
      self-administered daily questionnaire during the 3-4 week study enrollment period&#xD;
&#xD;
      STATISTICS: Area under the concentration-time curve (AUC), peak plasma concentration, and the&#xD;
      lowest plasma concentration for NET in HIV+ women receiving this PI therapy will be&#xD;
      determined and compared to similar values in HIV positive control subjects who are not taking&#xD;
      PI therapy. Statistical consultation will be obtained from the USC Keck School of Medicine&#xD;
      Department of Bio statistics and Laboratory of Applied Pharmacokinetics&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC Norethindrone</measure>
    <time_frame>following 21 days of continuous ingestion</time_frame>
    <description>0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 21</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Pregnancy</condition>
  <condition>HIV</condition>
  <condition>AIDS</condition>
  <arm_group>
    <arm_group_label>PI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study group with PI: atazanavir ritonavir</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>o PI therapy, control group</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norethindrone acetate</intervention_name>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>PI</arm_group_label>
    <other_name>Both control and experimental group with take norethindrone. However the experimental group will be taking a protease inhibitor: atazanavir and ritonavir</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Ages: 18-44 years Gender: female Accepts: healthy volunteers and HIV-1 infected women&#xD;
        Acceptable medications include: no other medications, NRTI combinations, entry inhibitors,&#xD;
        integrase inhibitors, and CCR5 agonists. NRTI combinations may include but are not limited&#xD;
        to: zidovudine (ZDV), lamivudine (3TC), emtricitabine (FTC), didanosine (ddl), stavudine&#xD;
        (d4T), abacavir (ABC), and tenofovir disoproxil fumarate (TDF). NNRTI: etravirine, and&#xD;
        rilpivirine.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        History of bilateral oophorectomy, ovarian dysfunction or no regular periods. CD4+ cell&#xD;
        count &lt;200 cells/mm3 No current or uncontrolled thyroid, liver, or renal disease BMI &lt;40&#xD;
        kg/m^2 Current pregnancy, breastfeeding or pregnancy within 30 days of enrollment.&#xD;
        Depomedroxyprogesterone acetate injection (DMPA) within 180 days prior to study entry.&#xD;
&#xD;
        Other hormonal therapies (e.g. oral contraceptive agents, Provera, vaginal ring,&#xD;
        contraceptive patch, monthly contraceptive injection, hormone replacement therapy, anabolic&#xD;
        therapies, including nandrolone decanoate or megestrol acetate) within the 21 days prior to&#xD;
        study entry.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>44 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jessica M Atrio, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Los Angeles County Hospital University of Southern California (LAC USC)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033-1029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Los Angeles County University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033-1029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>May 27, 2015</results_first_submitted>
  <results_first_submitted_qc>August 19, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 20, 2015</results_first_posted>
  <last_update_submitted>August 19, 2015</last_update_submitted>
  <last_update_submitted_qc>August 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern California</investigator_affiliation>
    <investigator_full_name>Jessica Maria Atrio</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>contraception</keyword>
  <keyword>mini pill</keyword>
  <keyword>norethindrone</keyword>
  <keyword>atazanavir</keyword>
  <keyword>ritonavir</keyword>
  <keyword>norvir</keyword>
  <keyword>reyataz</keyword>
  <keyword>pregnancy prevent</keyword>
  <keyword>birth control</keyword>
  <keyword>HIV</keyword>
  <keyword>AIDS</keyword>
  <keyword>antiviral</keyword>
  <keyword>antiretroviral</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Atazanavir Sulfate</mesh_term>
    <mesh_term>Norethindrone</mesh_term>
    <mesh_term>Norethindrone Acetate</mesh_term>
    <mesh_term>Protease Inhibitors</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Protease Inhibitor</title>
          <description>Study group with PI: atazanavir ritonavir&#xD;
Norethindrone acetate&#xD;
16 HIV positive on PI (atazanavir ritonavir 10, darunovir, lopinavir)</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>no PI therapy, control group&#xD;
Norethindrone acetate&#xD;
17 controls (4 no ARV)</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="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Protease Inhibitor</title>
          <description>Study group with PI: atazanavir ritonavir&#xD;
Norethindrone acetate</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>o PI therapy, control group&#xD;
Norethindrone acetate</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="17"/>
            <count group_id="B3" value="35"/>
          </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="17"/>
                    <measurement group_id="B3" value="35"/>
                  </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>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.9" lower_limit="35.9" upper_limit="42.3"/>
                    <measurement group_id="B2" value="38" lower_limit="33.4" upper_limit="41.3"/>
                    <measurement group_id="B3" value="39" lower_limit="34" upper_limit="41"/>
                  </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="18"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC Norethindrone</title>
        <description>0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 21</description>
        <time_frame>following 21 days of continuous ingestion</time_frame>
        <population>2 withdrew because unable to present for study visit and another changed her medication</population>
        <group_list>
          <group group_id="O1">
            <title>Protease Inhibitor</title>
            <description>Study group with PI: atazanavir ritonavir&#xD;
Norethindrone acetate</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>o PI therapy, control group&#xD;
Norethindrone acetate</description>
          </group>
        </group_list>
        <measure>
          <title>AUC Norethindrone</title>
          <description>0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 21</description>
          <population>2 withdrew because unable to present for study visit and another changed her medication</population>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.81" lower_limit="19.24" upper_limit="81.71"/>
                    <measurement group_id="O2" value="25.21" lower_limit="15.89" upper_limit="42.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Protease Inhibitor</title>
          <description>Study group with PI: atazanavir ritonavir&#xD;
Norethindrone acetate</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>o PI therapy, control group&#xD;
Norethindrone acetate</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Jessica Atrio</name_or_title>
      <organization>Montefiore</organization>
      <phone>718 405 82 60</phone>
      <email>jatrio@montefiore.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/NCT01667978
org study id: HS-12-00005
nct id: NCT01667978
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to learn if women taking the atazanavir and ritonavir have lower
      levels of a birth control medication called norethindrone. Norethindrone (also called the
      mini pill) is an FDA (Food and Drug Administration) approved progestin-only birth control
      pill used to prevent pregnancy. Norethindrone is the standard medication used in women who
      take the progestin only pill to prevent pregnancy. There are other birth control pills which
      contain different medications. The investigators want to learn if HIV medications (atazanavir
      and ritonavir) make the blood level of this birth control pill higher or lower. If the levels
      of norethindrone are too low it may not work to prevent pregnancy. The investigators also
      hope to learn about changes in the vaginal fluids and cervical fluids when women are taking
      this birth control pill.
BACKGROUND/RATIONALE : It is recognized that there is a dearth of clinically applied,
      population based, empiric data to guide contraceptive recommendations in HIV + women on
      ARVs.(1) Protease inhibitors (PI) and non nucleoside reverse transcriptase inhibitors (NNRTI
      ) induce micro enzyme systems such as CYP 3a4, which in turn alters the bio-availability and
      pharmacokinetics of other concurrently administered medications.(2) Empiric trials from small
      samples, often of 10-20 HIV negative subjects, have demonstrated that concurrent
      administration of combined oral contraceptives (COC) and a PI or a NNRTI have been associated
      with decreased plasma ethinyl estradiol (EE) levels. These pharmacokinetic findings have
      raised concern that decreased bio-availability of EE may result in decreased contraceptive
      efficacy, with possible increased unintended pregnancy. Some of these COC studies have
      demonstrated that there is no change in the serum levels of norethindrone (NET) on
      ARVs.(3-16) However, there are no published trials focused on oral NET or oral progestin-only
      pills (POP) to guide management in HIV+ women.(17)

      OBJECTIVES:

      Primary objective of this study is:

      To detect a ±40% difference in AUC of serum NET in HIV+ women taking ATV/RTV as compared to
      AUC of NET in HIV+ women taking an ARV regimen that has demonstrated no interaction with NET
      in the past.

      Primary endpoint: Natural log-transformed NET PK parameter AUC from 0 to 72 hours following
      oral administration, with multiple discrete serum data points for each subject on ATV/RTV.
      This will be compared to natural log-transformed NET PK AUC from 0 to 72 hours following oral
      administration, with multiple discrete serum data points for controls HIV+ women taking an
      ARV regimen that has demonstrated no interaction with NET in the past.

      The secondary objectives of this study are:

      To evaluate the effect of ATV/RTV on other PK exposure endpoints and parameters of NET (with
      natural log transformation). The sample and control groups mentioned above will again be
      compared. Endpoints include:

      minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), time to Cmax
      (Tmax), and half-life (T1/2).

      SAMPLE SIZE: Recruitment of 16 participants in each arm, with the goal of attaining 32
      evaluable HIV-1-seropositive female subjects in total.

      POPULATION/STUDY ARMS: HIV-1-infected female subjects 18-44 years of age

      METHODOLOGY/INTERVENTIONS/FOLLOW-UP: A two-arm, open-label, prospective, steady state trial
      to characterize the pharmacokinetics (PK) of oral norethindrone (NET) as a progestin only
      contraceptive pill (POP) in HIV+ women receiving atazanavir and ritonavir therapy (ATV/RTV).
      The investigators will identify a control group of HIV+ women who are taking ARV regimens
      that have not significantly altered oral NET levels in prior trials. Subjects will be
      enrolled in the trial for approximately 4 weeks A 28 day continuous packet of NET 0.35 mg
      will be provided to all enrolled volunteers for 21 days of continuous administration. Women
      who participate in this study will demonstrate a means of continuing their ARV regimens for
      the duration of the study, ARV therapy will not be provided by this study. On day 22 subjects
      will be admitted for serial pharmacokinetic (PK) specimens collection following the final
      study dose of NET.

      Subjects will be enrolled into one of the 2 arms based on their current ARV regimen.

      Study group: Women on stable ARV/RTV (300/100mg daily) with additional ARV regimens that have
      not significantly altered oral NET levels in prior trials. (n=12).

      Control group: Stable on current ARV, no protease inhibitors (PI), ARV regimens that have not
      significantly altered oral NET levels in previous research.

      OUTCOMES: Intensive PK sampling for NET will be performed in those in intervention and
      control arms after 21 days of NET administration. To determine side effect profile of NET by
      self-administered daily questionnaire during the 3-4 week study enrollment period

      STATISTICS: Area under the concentration-time curve (AUC), peak plasma concentration, and the
      lowest plasma concentration for NET in HIV+ women receiving this PI therapy will be
      determined and compared to similar values in HIV positive control subjects who are not taking
      PI therapy. Statistical consultation will be obtained from the USC Keck School of Medicine
      Department of Bio statistics and Laboratory of Applied Pharmacokinetics
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC Norethindrone
time frame: following 21 days of continuous ingestion
description: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 21
arm group label: PI
arm group type: Experimental
description: Study group with PI: atazanavir ritonavir
arm group label: Control
arm group type: Placebo Comparator
description: o PI therapy, control group
intervention type: Drug
intervention name: Norethindrone acetate
arm group label: Control
arm group label: PI
other name: Both control and experimental group with take norethindrone. However the experimental group will be taking a protease inhibitor: atazanavir and ritonavir
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 44 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jessica M Atrio, MD
role: Principal Investigator
affiliation: University of Southern California
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Southern California
investigator full name: Jessica Maria Atrio
investigator title: Principle Investigator
mesh term: Ritonavir
mesh term: Atazanavir Sulfate
mesh term: Norethindrone
mesh term: Norethindrone Acetate
mesh term: Protease Inhibitors
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 