<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/NCT03819114</url>
  </required_header>
  <id_info>
    <org_study_id>ACTG A5375</org_study_id>
    <secondary_id>38493</secondary_id>
    <secondary_id>UM1AI068636</secondary_id>
    <nct_id>NCT03819114</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study to Evaluate Double-Dose Levonorgestrel Emergency Contraception in Combination With Efavirenz-Based Antiretroviral Therapy or Rifampicin-Containing Anti-Tuberculosis Therapy</brief_title>
  <official_title>An Open-Label, Phase II Pharmacokinetic Study to Evaluate Double-Dose Levonorgestrel Emergency Contraception in Combination With Efavirenz-Based Antiretroviral Therapy or Rifampicin-Containing Anti-Tuberculosis Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AIDS Clinical Trials Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>AIDS Clinical Trials Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this pharmacokinetic (PK) study was to evaluate if a double dose (3 mg) of&#xD;
      levonorgestrel (LNG) overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based&#xD;
      antiretroviral therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The&#xD;
      safety of double-dose (3.0 mg) LNG versus standard-dose (1.5 mg) was also compared.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This pharmacokinetic (PK) study evaluated if a double dose (3.0 mg) of levonorgestrel (LNG)&#xD;
      overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based antiretroviral&#xD;
      therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The safety of&#xD;
      double-dose (3.0 mg) LNG versus standard-dose (1.5 mg) was also compared.&#xD;
&#xD;
      Participants were volunteers who did not require emergency contraception (EC) for&#xD;
      contraception at the time of trial participation. This trial enrolled persons assigned female&#xD;
      sex at birth who were 16 years of age or older. Group assignment was determined by disease&#xD;
      status (HIV or TB; participants could not have been living with both HIV and TB), and, for&#xD;
      those with HIV, by ART regimen at enrollment. Participants with HIV who were taking EFV-based&#xD;
      ART were randomized to receive a standard dose LNG (Group A) or a double dose of LNG (Group&#xD;
      B). Participants taking dolutegravir (DTG)-based ART were assigned to a standard dose of LNG&#xD;
      (Group C). Participants in the continuation phase of active TB treatment taking RIF and&#xD;
      isoniazid (INH) with or without ethambutol were assigned to a double dose of LNG (Group D).&#xD;
&#xD;
      At study entry, participants in Groups A and C received a standard single dose of LNG.&#xD;
      Participants in Groups B and D received a double dose of LNG. Intensive PK monitoring was&#xD;
      conducted pre-dose, and after the LNG dose. Participants were expected to remain at the&#xD;
      clinical site while the initial 8 hour PK samples were collected, and to return to the&#xD;
      clinical site for the 24 and 48 hour samples.&#xD;
&#xD;
      All participants completed self-report questionnaires to assess adherence to TB therapy and&#xD;
      ART, menstrual history and patterns after LNG administration, and to collect adverse effects&#xD;
      commonly reported with LNG (i.e., irregular bleeding patterns). Adherence to ART and RIF was&#xD;
      also assessed by collecting hair samples and single plasma concentrations at entry.&#xD;
      Participants were followed for 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 6, 2019</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 2, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>LNG Area Under the Concentration-time Curve (AUC0-8h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose</time_frame>
    <description>AUC for each participant was calculated from all available LNG concentrations measured over 8 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification (LLOQ) for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number and Percentage of Participants Experiencing Either a Serious Adverse Event (SAE) or Adverse Event (AE) Potentially or Definitely Associated With Single Dose LNG Administration.</measure>
    <time_frame>From Day 0 through study Day 28</time_frame>
    <description>Adverse events were Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 and DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007. Relationship of AE to study treatment was determined by the site, study core team, and DAIDS clinical representative.&#xD;
AEs evaluated in this outcome fulfilled the below criteria:&#xD;
Potentially or definitely related to LNG dose&#xD;
Grade 3 or higher AEs&#xD;
Grade 2 of higher nausea, diarrhea, menorrhagia or metrorrhagia, and ectopic pregnancies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration (Cmax) of LNG</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
    <description>Cmax for each participant was calculated as the maximum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmax using the software package Phoenix WinNonLin (Certara®).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Concentration (Cmin) of LNG</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
    <description>Cmin for each participant was calculated as the minimum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmin using the software package Phoenix WinNonLin (Certara®). Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Clearance (CL/F) of LNG</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
    <description>Apparent oral clearance (CL/F) for each participant was calculated as CL/F = dose/AUC0-24 or CL/F = dose/AUC0-48 of the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine CL/F using the software package Phoenix WinNonLin (Certara®).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution (Vd) of LNG</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
    <description>Vd for each participant was calculated from observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Vd using the software package Phoenix WinNonLin (Certara®).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (T1/2) of LNG</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
    <description>T1/2 for each participant was calculated using regression analysis when possible from the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine T1/2 using the software package Phoenix WinNonLin (Certara®).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Minimum Concentration (Tmin) of LNG</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose</time_frame>
    <description>Tmin for each participant was time to the minimum observed LNG concentration after the observed dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LNG Area Under the Concentration Time Curve (AUC0-24h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours post-dose</time_frame>
    <description>AUC for each participant was calculated from all available LNG concentrations measured over 24 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LNG Area Under the Concentration Time Curve (AUC0-48h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose</time_frame>
    <description>AUC for each participant was calculated from all available LNG concentrations measured over 48 hours using the linear up/log down version of the trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LNG Total Area Under the Concentration Time Curve AUCinf (Infinity) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</measure>
    <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose</time_frame>
    <description>AUC for each participant was calculated from all available LNG concentrations measured to infinity hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>HIV Infections</condition>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>A: LNG 1.5 mg among participants on EFV-based ART (randomized)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: LNG 3.0 mg among participants on EFV-based ART (randomized)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 3mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: LNG 1.5 mg among participants on DTG-based ART (assigned)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D: LNG 3.0 mg among participants on RIF-INH TB Therapy (assigned)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 3mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levonorgestrel (LNG)</intervention_name>
    <description>LNG tablet(s) were administered by mouth in a directly observed manner.</description>
    <arm_group_label>A: LNG 1.5 mg among participants on EFV-based ART (randomized)</arm_group_label>
    <arm_group_label>B: LNG 3.0 mg among participants on EFV-based ART (randomized)</arm_group_label>
    <arm_group_label>C: LNG 1.5 mg among participants on DTG-based ART (assigned)</arm_group_label>
    <arm_group_label>D: LNG 3.0 mg among participants on RIF-INH TB Therapy (assigned)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenarcheal female.&#xD;
&#xD;
               -  Note: Participant report and clinician's opinion were acceptable.&#xD;
&#xD;
          -  The following laboratory values obtained within 30 days prior to study entry by any US&#xD;
             laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification&#xD;
             or its equivalent, or at any ACTG network-approved non-US laboratory that operated in&#xD;
             accordance with Good Clinical Laboratory Practices (GCLP) and participated in&#xD;
             appropriate external quality assurance (EQA) programs.&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) greater than or equal to 500 cells/mm^3&#xD;
&#xD;
               -  Platelet count greater than or equal to 50,000 platelets/mm^3&#xD;
&#xD;
               -  Hemoglobin greater than or equal to 8.0 g/dL&#xD;
&#xD;
               -  Aspartate transaminase (AST) less than 5 x upper limit of normal (ULN)&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) less than 5 x ULN&#xD;
&#xD;
               -  Creatinine less than or equal to 1.5 x ULN&#xD;
&#xD;
               -  Total bilirubin less than or equal to 2.0 x ULN&#xD;
&#xD;
          -  Negative serum or urine pregnancy test within 30 days prior to study entry and within&#xD;
             48 hours prior to entry (if screening occurred more than 48 hours prior to entry) by&#xD;
             any US clinic or US laboratory that had a CLIA certification or its equivalent, or&#xD;
             used a point of care (POC)/CLIA-waived test, or at any network-approved non-US&#xD;
             laboratory or non-US clinic that operated in accordance with GCLP and participated in&#xD;
             appropriate EQA programs. The serum or urine pregnancy test must have had a&#xD;
             sensitivity of at least 25 mIU/mL.&#xD;
&#xD;
          -  Had not had sex that could lead to pregnancy without contraception within 14 days&#xD;
             prior to study entry as defined in the criteria below, according to participant&#xD;
             self-report.&#xD;
&#xD;
          -  Contraception requirements&#xD;
&#xD;
               -  All participants agreed not to participate in a conception process (e.g., active&#xD;
                  attempt to become pregnant or in vitro fertilization) for the duration of the&#xD;
                  study. Women of reproductive potential, who were participating in sexual activity&#xD;
                  that could lead to pregnancy, agreed to use at least one reliable method of&#xD;
                  contraception while in the study. Acceptable forms of contraceptives included:&#xD;
&#xD;
                    -  Male condom with or without a spermicidal agent&#xD;
&#xD;
                    -  Diaphragm or cervical cap with spermicide&#xD;
&#xD;
                    -  Non-hormonal intrauterine device (IUD)&#xD;
&#xD;
                    -  Bilateral tubal ligation&#xD;
&#xD;
                    -  Male partner vasectomy&#xD;
&#xD;
          -  Ability and willingness of participant or legal guardian/representative to have&#xD;
             provided informed consent.&#xD;
&#xD;
          -  Body mass index (BMI) (kg/m^2) available at entry. See the study protocol for BMI&#xD;
             calculation instructions.&#xD;
&#xD;
               -  Note: A maximum of 5 participants with BMI greater than or equal to 30 kg/m^2&#xD;
                  were allowed in each arm B-D and a maximum of 3 participants in Arm A.&#xD;
&#xD;
          -  For participants with HIV: HIV-1 infection, documented by any licensed rapid HIV test&#xD;
             or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to&#xD;
             study entry and confirmed by a licensed Western blot or a second antibody test by a&#xD;
             method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma&#xD;
             HIV-1 RNA viral load.&#xD;
&#xD;
               -  Note: The term &quot;licensed&quot; referred to a US Food and Drug Administration&#xD;
                  (FDA)-approved kit, which was required for all investigational new drug (IND)&#xD;
                  studies, or for sites located in countries other than the United States, a kit&#xD;
                  that had been certified or licensed by an oversight body within that country and&#xD;
                  validated internally. Non-US sites were encouraged to use US FDA-approved methods&#xD;
                  for IND studies.&#xD;
&#xD;
               -  World Health Organization (WHO) and Centers for Disease Control and Prevention&#xD;
                  (CDC) guidelines mandated that confirmation of the initial test result must have&#xD;
                  used a test that was different from the one used for the initial assessment. A&#xD;
                  reactive initial rapid test was confirmed by either another type of rapid assay&#xD;
                  or an E/CIA that was based on a different antigen preparation and/or different&#xD;
                  test principle (e.g., indirect versus competitive), or a Western blot or a plasma&#xD;
                  HIV-1 RNA viral load.&#xD;
&#xD;
          -  For participants with HIV: Received a stable qualifying concomitant ART regimen&#xD;
             containing either once-daily DTG 50 mg or EFV 600 mg with no changes in the components&#xD;
             of their ART for at least 30 days prior to study entry.&#xD;
&#xD;
          -  For participants who were being treated for TB: HIV-negative at screening, documented&#xD;
             within the prior 6 months by any licensed rapid HIV test or HIV enzyme or&#xD;
             chemiluminescence immunoassay (E/CIA) test kit and confirmed by a licensed Western&#xD;
             blot or a second antibody test by a method other than the initial rapid HIV and/or&#xD;
             E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load.&#xD;
&#xD;
               -  Note: The term &quot;licensed&quot; referred to a US FDA-approved kit, which was required&#xD;
                  for all IND studies, or for sites located in countries other than the United&#xD;
                  States, a kit that had been certified or licensed by an oversight body within&#xD;
                  that country and validated internally. Non-US sites were encouraged to use US&#xD;
                  FDA-approved methods for IND studies.&#xD;
&#xD;
               -  WHO and CDC guidelines mandated that confirmation of the initial test result must&#xD;
                  have used a test that was different from the one used for the initial assessment.&#xD;
                  A reactive initial rapid test was confirmed by either another type of rapid assay&#xD;
                  or an E/CIA that was based on a different antigen preparation and/or different&#xD;
                  test principle (e.g., indirect versus competitive), or a Western blot or a plasma&#xD;
                  HIV-1 RNA viral load.&#xD;
&#xD;
          -  For participants who were living without HIV and being treated for TB: Received RIF&#xD;
             and INH on a once daily dosing (7 days per week) schedule at study entry, after&#xD;
             completion of the intensive phase of TB treatment.&#xD;
&#xD;
               -  Note: Inclusion of ethambutol as part of continuation phase of TB therapy was&#xD;
                  allowed.&#xD;
&#xD;
          -  Ability and willingness of participant to have been contacted remotely for study&#xD;
             visits.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Known allergy/sensitivity or any hypersensitivity to LNG or components of the&#xD;
             formulation.&#xD;
&#xD;
          -  Bilateral oophorectomy, hysterectomy, or postmenopausal&#xD;
&#xD;
               -  Note: Postmenopausal was defined as amenorrhea for at least 12 consecutive months&#xD;
                  prior to study entry (in the absence of medications known to induce amenorrhea),&#xD;
                  and had a documented follicle stimulated hormone-release factor (FSH) measurement&#xD;
                  greater than 40 mIU/mL or a result in the testing laboratory's menopausal range.&#xD;
                  If an FSH level was not available, 24 consecutive months of amenorrhea prior to&#xD;
                  study entry (in the absence of medications known to induce amenorrhea).&#xD;
&#xD;
               -  Note: Clinical assessment and clinician's opinion were acceptable.&#xD;
&#xD;
          -  Was currently pregnant, was within 6 weeks of delivery, or was currently breastfeeding&#xD;
             an infant under 6 months of age.&#xD;
&#xD;
               -  Note: For recent pregnancy resolution during the first or second trimester, the&#xD;
                  participant was only eligible when the pregnancy test result was negative.&#xD;
&#xD;
          -  Receipt of LNG within 30 days prior to study entry.&#xD;
&#xD;
          -  Receipt of depo-medroxyprogesterone for 90 days prior to study entry, or&#xD;
             norethisterone enanthate (NET-EN) within 60 days prior to study entry, or other&#xD;
             hormonal contraceptives within 30 days prior to study entry.&#xD;
&#xD;
          -  Used any drugs other than RIF and EFV known to: 1) induce CYP3A4 system within 30 days&#xD;
             prior to study entry, and 2) inhibit the CYP3A4 system within 7 days prior to study&#xD;
             entry. See the study protocol for prohibited and precautionary medications.&#xD;
&#xD;
          -  Active drug or alcohol use or dependence that, in the opinion of the site&#xD;
             investigator, would have interfered with adherence to study requirements.&#xD;
&#xD;
          -  Acute or serious illness that required systemic treatment and/or hospitalization&#xD;
             within 14 days prior to study entry.&#xD;
&#xD;
          -  Other medical, psychiatric, or psychological condition that, in the opinion of the&#xD;
             site investigator, would have interfered with completion of study procedures and or&#xD;
             adherence to study drug.&#xD;
&#xD;
          -  For participants with HIV: Was currently receiving medications for TB infection.&#xD;
&#xD;
          -  For participants with HIV: Had missed one or more of the prescribed doses of HIV&#xD;
             medications within 3 days prior to study entry.&#xD;
&#xD;
               -  Note: The entry visit could have been rescheduled within the screening period&#xD;
                  once the participant had taken all prescribed doses within 3 days prior to study&#xD;
                  entry.&#xD;
&#xD;
          -  For participants who were not living with HIV and were being treated for TB: Had&#xD;
             missed one or more of the prescribed doses of TB medication within 3 days prior to&#xD;
             study entry.&#xD;
&#xD;
               -  Note: The entry visit could have been rescheduled within the screening period&#xD;
                  once the participant had taken all prescribed doses within 3 days prior to study&#xD;
                  entry.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kimberly Scarsi, PharmD, MS</last_name>
    <role>Study Chair</role>
    <affiliation>Northwestern University CRS, University of Nebraska Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>2701 Northwestern University CRS</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush Univ. Med. Ctr. ACTG CRS (2702)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Upton CRS (7803)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unc Aids Crs (3201)</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. of the Univ. of Pennsylvania CRS (6201)</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pitt CRS (1001)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trinity Health and Wellness Center CRS (31443)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gaborone CRS (12701)</name>
      <address>
        <city>Gaborone</city>
        <country>Botswana</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>12101 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>21040</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS (12501)</name>
      <address>
        <city>Kericho</city>
        <zip>20200</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blantyre CRS (30301)</name>
      <address>
        <city>Blantyre</city>
        <country>Malawi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Malawi CRS (12001)</name>
      <address>
        <city>Lilongwe</city>
        <country>Malawi</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101)</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Family Clinical Research Unit (FAM-CUR) CRS (8950)</name>
      <address>
        <city>Cape Town</city>
        <state>West Cape</state>
        <zip>7505</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Durban Adult HIV CRS (11201)</name>
      <address>
        <city>Durban</city>
        <zip>4013 SF</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soweto ACTG CRS (12301)</name>
      <address>
        <city>Johannesburg</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS</name>
      <address>
        <city>Bangkok</city>
        <state>Patumwan</state>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>31784 Chiang Mai University HIV Treatment CRS</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Botswana</country>
    <country>Brazil</country>
    <country>Kenya</country>
    <country>Malawi</country>
    <country>South Africa</country>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables</url>
    <description>The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1, July 2017.</description>
  </link>
  <link>
    <url>https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids</url>
    <description>Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010</description>
  </link>
  <link>
    <url>https://rsc.niaid.nih.gov/sites/default/files/addendum-1-female-genital-grading-table-v1-nov-2007.pdf</url>
    <description>DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0, November 2007</description>
  </link>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <results_first_submitted>November 2, 2021</results_first_submitted>
  <results_first_submitted_qc>November 2, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 30, 2021</results_first_posted>
  <last_update_submitted>December 22, 2021</last_update_submitted>
  <last_update_submitted_qc>December 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Levonorgestrel</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Efavirenz</keyword>
  <keyword>Dolutegravir</keyword>
  <keyword>Rifampin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Emergencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levonorgestrel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie results in the publication, after deidentification.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH</ipd_time_frame>
    <ipd_access_criteria>With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.&#xD;
For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.&#xD;
By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group &quot;Data Request&quot; form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 30, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03819114/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 24, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03819114/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 31, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03819114/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants enrolled from 18 sites. Sites were located in the United States and internationally (Botswana, Brazil, Kenya, Malawi, South Africa, Thailand). The first participant accrued in May 2019, and the last participant accrued in November 2020.</recruitment_details>
      <pre_assignment_details>Participants receiving EFV-based ART therapy were randomized between Group A (1.5mg dose of LNG) and Group B (3.0mg dose of LNG) in a 1:2 ratio using permuted blocks and institutional balancing. Participants living with HIV receiving DTG-based ART therapy and participants with TB receiving RIF-INH therapy were assigned to study groups C and D, respectively.&#xD;
Women with BMI greater than or equal to 30 kg/m2 were limited to no more than 5 within Groups B-D and no more than three within Group A.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
          <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="P2">
          <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
          <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="P3">
          <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
          <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="P4">
          <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
          <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="36"/>
                <participants group_id="P3" count="35"/>
                <participants group_id="P4" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received LNG Treatment</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="36"/>
                <participants group_id="P3" count="35"/>
                <participants group_id="P4" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="35"/>
                <participants group_id="P3" count="33"/>
                <participants group_id="P4" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
      <group_list>
        <group group_id="B1">
          <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
          <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="B2">
          <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
          <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="B3">
          <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
          <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="B4">
          <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
          <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="B5">
          <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="17"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="32"/>
            <count group_id="B4" value="34"/>
            <count group_id="B5" value="118"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="42" lower_limit="35" upper_limit="45"/>
                    <measurement group_id="B2" value="36" lower_limit="29" upper_limit="42"/>
                    <measurement group_id="B3" value="34" lower_limit="29" upper_limit="40"/>
                    <measurement group_id="B4" value="25" lower_limit="21" upper_limit="35"/>
                    <measurement group_id="B5" value="34" lower_limit="27" upper_limit="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Sex assigned at birth</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="34"/>
                    <measurement group_id="B5" value="118"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black (Non-Hispanic)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="30"/>
                    <measurement group_id="B5" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic or Latino (Regardless of race)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple Races</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White (Non-Hispanic)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Botswana</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Brazil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Kenya</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Malawi</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>South Africa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="18"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thailand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender Identity</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Cisgender</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="34"/>
                    <measurement group_id="B5" value="118"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Transgender spectrum</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HIV-1 Infection Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>HIV-1 infection present</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HIV-1 infection absent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="34"/>
                    <measurement group_id="B5" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>LNG Area Under the Concentration-time Curve (AUC0-8h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
        <description>AUC for each participant was calculated from all available LNG concentrations measured over 8 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification (LLOQ) for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>LNG Area Under the Concentration-time Curve (AUC0-8h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
          <description>AUC for each participant was calculated from all available LNG concentrations measured over 8 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification (LLOQ) for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>hours * ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.13" lower_limit="36.72" upper_limit="88.27"/>
                    <measurement group_id="O2" value="102.13" lower_limit="64.52" upper_limit="114.75"/>
                    <measurement group_id="O3" value="80.50" lower_limit="66.64" upper_limit="125.06"/>
                    <measurement group_id="O4" value="124.39" lower_limit="87.10" upper_limit="168.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Confidence Interval (CI) on Geometric Mean Ratio compared to reference interval (0.7, 1.43).</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.99</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.81</ci_lower_limit>
            <ci_upper_limit>1.20</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Confidence Interval on Geometric Mean Ratio compared to reference interval (0.7, 1.43).</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.34</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.12</ci_lower_limit>
            <ci_upper_limit>1.60</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Confidence Interval on Geometric Mean Ratio excluding 1.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.66</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.27</ci_lower_limit>
            <ci_upper_limit>2.18</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Confidence Interval on Geometric Mean Ratio excluding 1.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.59</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.45</ci_lower_limit>
            <ci_upper_limit>0.78</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number and Percentage of Participants Experiencing Either a Serious Adverse Event (SAE) or Adverse Event (AE) Potentially or Definitely Associated With Single Dose LNG Administration.</title>
        <description>Adverse events were Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 and DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007. Relationship of AE to study treatment was determined by the site, study core team, and DAIDS clinical representative.&#xD;
AEs evaluated in this outcome fulfilled the below criteria:&#xD;
Potentially or definitely related to LNG dose&#xD;
Grade 3 or higher AEs&#xD;
Grade 2 of higher nausea, diarrhea, menorrhagia or metrorrhagia, and ectopic pregnancies</description>
        <time_frame>From Day 0 through study Day 28</time_frame>
        <population>Participants who received LNG study treatment, grouped by LNG dose. LNG 1.5mg includes Group A (LNG 1.5 mg Among Participants on EFV-based ART (Randomized)) and Group C (LNG 1.5 mg Among Participants on DTG-based ART (Assigned)) participants. LNG 3.0mg includes Group B (LNG 3.0 mg Among Participants on EFV-based ART (Randomized)) and Group D (LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)) participants.</population>
        <group_list>
          <group group_id="O1">
            <title>LNG 1.5 mg</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>LNG 3.0 mg</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number and Percentage of Participants Experiencing Either a Serious Adverse Event (SAE) or Adverse Event (AE) Potentially or Definitely Associated With Single Dose LNG Administration.</title>
          <description>Adverse events were Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 and DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007. Relationship of AE to study treatment was determined by the site, study core team, and DAIDS clinical representative.&#xD;
AEs evaluated in this outcome fulfilled the below criteria:&#xD;
Potentially or definitely related to LNG dose&#xD;
Grade 3 or higher AEs&#xD;
Grade 2 of higher nausea, diarrhea, menorrhagia or metrorrhagia, and ectopic pregnancies</description>
          <population>Participants who received LNG study treatment, grouped by LNG dose. LNG 1.5mg includes Group A (LNG 1.5 mg Among Participants on EFV-based ART (Randomized)) and Group C (LNG 1.5 mg Among Participants on DTG-based ART (Assigned)) participants. LNG 3.0mg includes Group B (LNG 3.0 mg Among Participants on EFV-based ART (Randomized)) and Group D (LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)) participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.00</p_value>
            <p_value_desc>No adjustments for multiple comparisons were made. Statistical significance was declared if p&lt;0.05.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Concentration (Cmax) of LNG</title>
        <description>Cmax for each participant was calculated as the maximum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmax using the software package Phoenix WinNonLin (Certara®).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Concentration (Cmax) of LNG</title>
          <description>Cmax for each participant was calculated as the maximum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmax using the software package Phoenix WinNonLin (Certara®).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.10" lower_limit="11.20" upper_limit="24.00"/>
                    <measurement group_id="O2" value="24.90" lower_limit="16.20" upper_limit="29.60"/>
                    <measurement group_id="O3" value="18.65" lower_limit="14.05" upper_limit="26.15"/>
                    <measurement group_id="O4" value="28.01" lower_limit="23.00" upper_limit="39.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.17</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.96</ci_lower_limit>
            <ci_upper_limit>1.41</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.43</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.21</ci_lower_limit>
            <ci_upper_limit>1.69</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.51</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.17</ci_lower_limit>
            <ci_upper_limit>1.96</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.77</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.60</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Minimum Concentration (Cmin) of LNG</title>
        <description>Cmin for each participant was calculated as the minimum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmin using the software package Phoenix WinNonLin (Certara®). Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Minimum Concentration (Cmin) of LNG</title>
          <description>Cmin for each participant was calculated as the minimum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmin using the software package Phoenix WinNonLin (Certara®). Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" lower_limit="0.13" upper_limit="0.37"/>
                    <measurement group_id="O2" value="0.56" lower_limit="0.19" upper_limit="1.08"/>
                    <measurement group_id="O3" value="1.49" lower_limit="0.80" upper_limit="3.07"/>
                    <measurement group_id="O4" value="0.41" lower_limit="0.17" upper_limit="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.37</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.22</ci_lower_limit>
            <ci_upper_limit>0.61</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.25</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.15</ci_lower_limit>
            <ci_upper_limit>0.44</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>2.11</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.20</ci_lower_limit>
            <ci_upper_limit>3.70</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.17</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.09</ci_lower_limit>
            <ci_upper_limit>0.32</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oral Clearance (CL/F) of LNG</title>
        <description>Apparent oral clearance (CL/F) for each participant was calculated as CL/F = dose/AUC0-24 or CL/F = dose/AUC0-48 of the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine CL/F using the software package Phoenix WinNonLin (Certara®).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Clearance (CL/F) of LNG</title>
          <description>Apparent oral clearance (CL/F) for each participant was calculated as CL/F = dose/AUC0-24 or CL/F = dose/AUC0-48 of the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine CL/F using the software package Phoenix WinNonLin (Certara®).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>L/h</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.64" lower_limit="10.44" upper_limit="21.06"/>
                    <measurement group_id="O2" value="15.24" lower_limit="12.59" upper_limit="27.66"/>
                    <measurement group_id="O3" value="4.39" lower_limit="2.89" upper_limit="6.59"/>
                    <measurement group_id="O4" value="12.05" lower_limit="9.01" upper_limit="16.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>4.03</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.17</ci_lower_limit>
            <ci_upper_limit>5.12</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>2.92</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.33</ci_lower_limit>
            <ci_upper_limit>3.65</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.11</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.82</ci_lower_limit>
            <ci_upper_limit>1.52</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>3.62</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.65</ci_lower_limit>
            <ci_upper_limit>4.93</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution (Vd) of LNG</title>
        <description>Vd for each participant was calculated from observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Vd using the software package Phoenix WinNonLin (Certara®).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution (Vd) of LNG</title>
          <description>Vd for each participant was calculated from observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Vd using the software package Phoenix WinNonLin (Certara®).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>L</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="276.70" lower_limit="118.28" upper_limit="411.82"/>
                    <measurement group_id="O2" value="294.92" lower_limit="208.70" upper_limit="489.52"/>
                    <measurement group_id="O3" value="169.05" lower_limit="93.83" upper_limit="215.16"/>
                    <measurement group_id="O4" value="156.31" lower_limit="105.26" upper_limit="247.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>2.10</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.66</ci_lower_limit>
            <ci_upper_limit>2.65</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.11</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.89</ci_lower_limit>
            <ci_upper_limit>1.39</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.20</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.87</ci_lower_limit>
            <ci_upper_limit>1.66</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.75</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.24</ci_lower_limit>
            <ci_upper_limit>2.45</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Half-life (T1/2) of LNG</title>
        <description>T1/2 for each participant was calculated using regression analysis when possible from the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine T1/2 using the software package Phoenix WinNonLin (Certara®).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Half-life (T1/2) of LNG</title>
          <description>T1/2 for each participant was calculated using regression analysis when possible from the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine T1/2 using the software package Phoenix WinNonLin (Certara®).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.05" lower_limit="8.63" upper_limit="13.70"/>
                    <measurement group_id="O2" value="11.79" lower_limit="10.58" upper_limit="13.80"/>
                    <measurement group_id="O3" value="24.03" lower_limit="19.95" upper_limit="28.03"/>
                    <measurement group_id="O4" value="8.97" lower_limit="6.72" upper_limit="11.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.52</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.46</ci_lower_limit>
            <ci_upper_limit>0.59</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.38</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.34</ci_lower_limit>
            <ci_upper_limit>0.43</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.08</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.93</ci_lower_limit>
            <ci_upper_limit>1.25</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.48</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.41</ci_lower_limit>
            <ci_upper_limit>0.56</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time of Minimum Concentration (Tmin) of LNG</title>
        <description>Tmin for each participant was time to the minimum observed LNG concentration after the observed dose.</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Time of Minimum Concentration (Tmin) of LNG</title>
          <description>Tmin for each participant was time to the minimum observed LNG concentration after the observed dose.</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.07" lower_limit="46.13" upper_limit="48.00"/>
                    <measurement group_id="O2" value="47.95" lower_limit="46.13" upper_limit="48.00"/>
                    <measurement group_id="O3" value="47.61" lower_limit="0.50" upper_limit="48.31"/>
                    <measurement group_id="O4" value="48.00" lower_limit="46.55" upper_limit="48.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>LNG Area Under the Concentration Time Curve (AUC0-24h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
        <description>AUC for each participant was calculated from all available LNG concentrations measured over 24 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours post-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>LNG Area Under the Concentration Time Curve (AUC0-24h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
          <description>AUC for each participant was calculated from all available LNG concentrations measured over 24 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>hours * ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.64" lower_limit="56.14" upper_limit="128.49"/>
                    <measurement group_id="O2" value="153.40" lower_limit="100.13" upper_limit="190.48"/>
                    <measurement group_id="O3" value="157.56" lower_limit="132.30" upper_limit="282.32"/>
                    <measurement group_id="O4" value="213.69" lower_limit="148.64" upper_limit="283.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.75</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.60</ci_lower_limit>
            <ci_upper_limit>0.93</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.10</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.90</ci_lower_limit>
            <ci_upper_limit>1.36</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.74</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.29</ci_lower_limit>
            <ci_upper_limit>2.33</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.43</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.32</ci_lower_limit>
            <ci_upper_limit>0.58</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>LNG Area Under the Concentration Time Curve (AUC0-48h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
        <description>AUC for each participant was calculated from all available LNG concentrations measured over 48 hours using the linear up/log down version of the trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>LNG Area Under the Concentration Time Curve (AUC0-48h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
          <description>AUC for each participant was calculated from all available LNG concentrations measured over 48 hours using the linear up/log down version of the trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>hours * ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.95" lower_limit="66.38" upper_limit="141.27"/>
                    <measurement group_id="O2" value="180.25" lower_limit="106.87" upper_limit="216.75"/>
                    <measurement group_id="O3" value="224.81" lower_limit="178.30" upper_limit="400.90"/>
                    <measurement group_id="O4" value="242.68" lower_limit="181.56" upper_limit="321.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.62</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.49</ci_lower_limit>
            <ci_upper_limit>0.78</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.89</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>1.10</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.77</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.31</ci_lower_limit>
            <ci_upper_limit>2.40</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.35</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.26</ci_lower_limit>
            <ci_upper_limit>0.47</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>LNG Total Area Under the Concentration Time Curve AUCinf (Infinity) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
        <description>AUC for each participant was calculated from all available LNG concentrations measured to infinity hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
        <time_frame>Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose</time_frame>
        <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned)</title>
            <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)</title>
            <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>LNG Total Area Under the Concentration Time Curve AUCinf (Infinity) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants</title>
          <description>AUC for each participant was calculated from all available LNG concentrations measured to infinity hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values &lt; LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).</description>
          <population>Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame.</population>
          <units>hours * ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="118.71" lower_limit="71.23" upper_limit="143.69"/>
                    <measurement group_id="O2" value="196.83" lower_limit="108.48" upper_limit="238.24"/>
                    <measurement group_id="O3" value="345.80" lower_limit="227.80" upper_limit="518.69"/>
                    <measurement group_id="O4" value="248.96" lower_limit="183.87" upper_limit="333.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.39</ci_lower_limit>
            <ci_upper_limit>0.63</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.69</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.55</ci_lower_limit>
            <ci_upper_limit>0.86</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.80</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.32</ci_lower_limit>
            <ci_upper_limit>2.45</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>No hypothesis testing was performed.</non_inferiority_desc>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.28</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.20</ci_lower_limit>
            <ci_upper_limit>0.38</ci_upper_limit>
            <estimate_desc>The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From study entry to study completion at Day 28 or premature study discontinuation.</time_frame>
      <desc>The DAIDS AE Grading Table (V2.1) and Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007 were used.&#xD;
AEs were recorded on the case report forms (CRFs) if any of the following criteria had been met:&#xD;
All Grade ≥3 AEs considered potentially or definitely related to LNG&#xD;
All Grade ≥2 nausea, diarrhea, menorrhagia, or metrorrhagia&#xD;
Ectopic pregnancy&#xD;
All AEs meeting Serious Adverse Event (SAE) definition</desc>
      <group_list>
        <group group_id="E1">
          <title>A: LNG 1.5 mg Among Women on EFV-based ART (Randomized)</title>
          <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="E2">
          <title>B: LNG 3.0 mg Among Women on EFV-based ART (Randomized)</title>
          <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="E3">
          <title>C: LNG 1.5 mg Among Women on DTG-based ART (Assigned)</title>
          <description>Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
        <group group_id="E4">
          <title>D: LNG 3.0 mg Among Women on RIF-INH TB Therapy (Assigned)</title>
          <description>Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <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="1" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Heavy menstrual bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Intermenstrual bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Menstrual discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="34"/>
              </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>ACTG Clinicaltrials.gov Coordinator</name_or_title>
      <organization>ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company.</organization>
      <phone>(301) 628-3348</phone>
      <email>ACTGCT.gov@fstrf.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/NCT03819114
org study id: ACTG A5375
secondary id: 38493
secondary id: UM1AI068636
nct id: NCT03819114
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this pharmacokinetic (PK) study was to evaluate if a double dose (3 mg) of
      levonorgestrel (LNG) overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based
      antiretroviral therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The
      safety of double-dose (3.0 mg) LNG versus standard-dose (1.5 mg) was also compared.
This pharmacokinetic (PK) study evaluated if a double dose (3.0 mg) of levonorgestrel (LNG)
      overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based antiretroviral
      therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The safety of
      double-dose (3.0 mg) LNG versus standard-dose (1.5 mg) was also compared.

      Participants were volunteers who did not require emergency contraception (EC) for
      contraception at the time of trial participation. This trial enrolled persons assigned female
      sex at birth who were 16 years of age or older. Group assignment was determined by disease
      status (HIV or TB; participants could not have been living with both HIV and TB), and, for
      those with HIV, by ART regimen at enrollment. Participants with HIV who were taking EFV-based
      ART were randomized to receive a standard dose LNG (Group A) or a double dose of LNG (Group
      B). Participants taking dolutegravir (DTG)-based ART were assigned to a standard dose of LNG
      (Group C). Participants in the continuation phase of active TB treatment taking RIF and
      isoniazid (INH) with or without ethambutol were assigned to a double dose of LNG (Group D).

      At study entry, participants in Groups A and C received a standard single dose of LNG.
      Participants in Groups B and D received a double dose of LNG. Intensive PK monitoring was
      conducted pre-dose, and after the LNG dose. Participants were expected to remain at the
      clinical site while the initial 8 hour PK samples were collected, and to return to the
      clinical site for the 24 and 48 hour samples.

      All participants completed self-report questionnaires to assess adherence to TB therapy and
      ART, menstrual history and patterns after LNG administration, and to collect adverse effects
      commonly reported with LNG (i.e., irregular bleeding patterns). Adherence to ART and RIF was
      also assessed by collecting hair samples and single plasma concentrations at entry.
      Participants were followed for 4 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: LNG Area Under the Concentration-time Curve (AUC0-8h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose
description: AUC for each participant was calculated from all available LNG concentrations measured over 8 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification (LLOQ) for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
measure: Number and Percentage of Participants Experiencing Either a Serious Adverse Event (SAE) or Adverse Event (AE) Potentially or Definitely Associated With Single Dose LNG Administration.
time frame: From Day 0 through study Day 28
description: Adverse events were Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 and DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007. Relationship of AE to study treatment was determined by the site, study core team, and DAIDS clinical representative.
AEs evaluated in this outcome fulfilled the below criteria:
Potentially or definitely related to LNG dose
Grade 3 or higher AEs
Grade 2 of higher nausea, diarrhea, menorrhagia or metrorrhagia, and ectopic pregnancies
measure: Maximum Concentration (Cmax) of LNG
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose
description: Cmax for each participant was calculated as the maximum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmax using the software package Phoenix WinNonLin (Certara®).
measure: Minimum Concentration (Cmin) of LNG
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose
description: Cmin for each participant was calculated as the minimum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmin using the software package Phoenix WinNonLin (Certara®). Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
measure: Oral Clearance (CL/F) of LNG
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose
description: Apparent oral clearance (CL/F) for each participant was calculated as CL/F = dose/AUC0-24 or CL/F = dose/AUC0-48 of the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine CL/F using the software package Phoenix WinNonLin (Certara®).
measure: Volume of Distribution (Vd) of LNG
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose
description: Vd for each participant was calculated from observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Vd using the software package Phoenix WinNonLin (Certara®).
measure: Half-life (T1/2) of LNG
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose
description: T1/2 for each participant was calculated using regression analysis when possible from the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine T1/2 using the software package Phoenix WinNonLin (Certara®).
measure: Time of Minimum Concentration (Tmin) of LNG
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose
description: Tmin for each participant was time to the minimum observed LNG concentration after the observed dose.
measure: LNG Area Under the Concentration Time Curve (AUC0-24h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours post-dose
description: AUC for each participant was calculated from all available LNG concentrations measured over 24 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
measure: LNG Area Under the Concentration Time Curve (AUC0-48h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose
description: AUC for each participant was calculated from all available LNG concentrations measured over 48 hours using the linear up/log down version of the trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
measure: LNG Total Area Under the Concentration Time Curve AUCinf (Infinity) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants
time frame: Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose
description: AUC for each participant was calculated from all available LNG concentrations measured to infinity hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
arm group label: A: LNG 1.5 mg among participants on EFV-based ART (randomized)
arm group type: Experimental
description: Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.
arm group label: B: LNG 3.0 mg among participants on EFV-based ART (randomized)
arm group type: Experimental
description: Participants received 3mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.
arm group label: C: LNG 1.5 mg among participants on DTG-based ART (assigned)
arm group type: Experimental
description: Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.
arm group label: D: LNG 3.0 mg among participants on RIF-INH TB Therapy (assigned)
arm group type: Experimental
description: Participants received 3mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks.
intervention type: Drug
intervention name: Levonorgestrel (LNG)
description: LNG tablet(s) were administered by mouth in a directly observed manner.
arm group label: A: LNG 1.5 mg among participants on EFV-based ART (randomized)
arm group label: B: LNG 3.0 mg among participants on EFV-based ART (randomized)
arm group label: C: LNG 1.5 mg among participants on DTG-based ART (assigned)
arm group label: D: LNG 3.0 mg among participants on RIF-INH TB Therapy (assigned)
criteria: 
gender: Female
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Kimberly Scarsi, PharmD, MS
role: Study Chair
affiliation: Northwestern University CRS, University of Nebraska Medical Center
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country: Botswana
country: Brazil
country: Kenya
country: Malawi
country: South Africa
country: Thailand
country: United States
url: https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables
description: The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1, July 2017.
url: https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids
description: Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
url: https://rsc.niaid.nih.gov/sites/default/files/addendum-1-female-genital-grading-table-v1-nov-2007.pdf
description: DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0, November 2007
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Emergencies
mesh term: Levonorgestrel
sharing ipd: Yes
ipd description: Individual participant data that underlie results in the publication, after deidentification.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH
ipd access criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 