<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/NCT03282799</url>
  </required_header>
  <id_info>
    <org_study_id>PRO17080453</org_study_id>
    <nct_id>NCT03282799</nct_id>
  </id_info>
  <brief_title>Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women</brief_title>
  <official_title>Pharmacokinetic and Pharmacodynamic Evaluation of Etonogestrel Dose Escalation With Efavirenz-based Antiretroviral Therapy in HIV-infected Ugandan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Catherine Anne Chappell</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Infectious Disease Institute, Kampala, Uganda</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the frequency of ovulation and cervical mucus quality of&#xD;
      HIV-infected women on efavirenz (EFV)-based antiretroviral therapy (ART) using either a&#xD;
      single etonogestrel (ENG) implant or two ENG implants for at least one year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to drug-drug interactions between efavirenz (EFV) and progestins, HIV-infected women on&#xD;
      EFV-based antiretroviral therapy (ART) and using the etonogestrel implant have significantly&#xD;
      lower systemic ENG concentrations than HIV-infected women not on ART. This finding has raised&#xD;
      concerns regarding the contraceptive efficacy of the ENG implant for women on EFV-based ART&#xD;
      and clinical studies have an increased rate of pregnancies for women on EFV-based ART and&#xD;
      using a contraceptive implant. This study a randomized, open-label, longitudinal&#xD;
      pharmacodynamic study to compare frequency of ovulation between a control group of&#xD;
      HIV-infected women on efavirenz-based antiretroviral therapy receiving standard dose&#xD;
      etonogestrel (ENG) implant and a treatment group receiving increased dose ENG implant. The&#xD;
      overall goal is to assess the pharmacodynamic significance of the known drug-drug interaction&#xD;
      between EFV and ENG and to determine if the increased dose will overcome this interaction.&#xD;
      Overall, this study will improve long-acting reversible contraceptive treatment options for&#xD;
      women living with HIV and prevent unintended pregnancy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 19, 2019</start_date>
  <completion_date type="Actual">October 25, 2022</completion_date>
  <primary_completion_date type="Actual">December 22, 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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ovulation</measure>
    <time_frame>weekly at months 3, 6, and 12</time_frame>
    <description>Ovulation evaluated by endogenous progesterone concentrations of &gt;3ng/mL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cervical mucus quality</measure>
    <time_frame>weekly at months 3, 6, and 12</time_frame>
    <description>World Health Organization Cervical Mucus Scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Etonogestrel pharmacokinetics</measure>
    <time_frame>Week 1, 4, 12, 24, 36, and 48</time_frame>
    <description>Etonogestrel serum concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>up to months 12</time_frame>
    <description>Safety</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>HIV/AIDS</condition>
  <condition>Contraception</condition>
  <arm_group>
    <arm_group_label>Standard Dose Etonogestrel Implant</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single 68 mg etonogestrel implant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Increased Dose Etonogestrel Implant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two 68 mg (136 mg total) etonogestrel implants</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>etonogestrel implant</intervention_name>
    <description>The etonogestrel implant is an contraceptive implant that is placed into the upper arm.</description>
    <arm_group_label>Increased Dose Etonogestrel Implant</arm_group_label>
    <arm_group_label>Standard Dose Etonogestrel Implant</arm_group_label>
    <other_name>Nexplanon</other_name>
    <other_name>Implanon</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the participant has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          2. Participants who are willing and able to comply with scheduled visits, treatment plan,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
          3. Women age 18 years to 40 years&#xD;
&#xD;
          4. Diagnosed with HIV infection&#xD;
&#xD;
          5. Medically eligible for the ENG subdermal implant as a contraceptive method based on&#xD;
             the WHO Medical Eligibility Criteria for Contraceptive Use20&#xD;
&#xD;
          6. Receiving EFV-based ART for a minimum of 3 months prior to screening&#xD;
&#xD;
          7. Must agree to have concurrent highly effective non-hormonal contraception with a&#xD;
             copper IUD, if not previously medically sterilized.&#xD;
&#xD;
          8. Participants must report regular menses (bleeding for 4-8 days at 21 to 35 day&#xD;
             intervals) for the preceding 2 month&#xD;
&#xD;
          9. Participants must have a negative urine pregnancy test at entry and report no&#xD;
             unprotected sex since the last menstrual period or in the last two weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. HIV RNA &gt; 50 copies/mL at screening visit&#xD;
&#xD;
          2. Serum hemoglobin &lt; 10.0 g/dl&#xD;
&#xD;
          3. Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit&#xD;
             of normal&#xD;
&#xD;
          4. Elevations in serum creatinine above 2.5 times the upper limit of normal&#xD;
&#xD;
          5. Use of drugs known to be contraindicated with ENG or EFV within 30 days of study&#xD;
             entry. Due to the dynamic nature of drug interactions related to ART, the study team&#xD;
             will review all concomitant medications at screening based on the US Department of&#xD;
             Health and Human Services drug interaction table45 and the ENG implant product&#xD;
             labeling15.&#xD;
&#xD;
          6. Currently pregnant or postpartum &lt;30 days at study entry.&#xD;
&#xD;
          7. Breastfeeding women within 6 months of delivery.&#xD;
&#xD;
          8. Use of hormonal contraception in the preceding 3 months prior to entry&#xD;
&#xD;
          9. Participants determined to be ineligible for IUD placement by the WHO Medical&#xD;
             Eligibility Criteria for Contraceptive Use46&#xD;
&#xD;
         10. Patients with a history of hypersensitivity to ENG implant, undiagnosed vaginal&#xD;
             bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant&#xD;
             liver tumor, or thromboembolic disease.&#xD;
&#xD;
         11. Presence of any active clinically significant disease or life-threatening disease&#xD;
             that, in the investigator's opinion, would compromise the subject's safety or outcome&#xD;
             of the study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Infectious Disease Institute</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Uganda</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>March 10, 2023</last_update_submitted>
  <last_update_submitted_qc>March 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Catherine Anne Chappell</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>etonogestrel</keyword>
  <keyword>efavirenz</keyword>
  <keyword>antiretroviral therapy</keyword>
  <keyword>HIV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etonogestrel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03282799
org study id: PRO17080453
nct id: NCT03282799
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will evaluate the frequency of ovulation and cervical mucus quality of
      HIV-infected women on efavirenz (EFV)-based antiretroviral therapy (ART) using either a
      single etonogestrel (ENG) implant or two ENG implants for at least one year.
Due to drug-drug interactions between efavirenz (EFV) and progestins, HIV-infected women on
      EFV-based antiretroviral therapy (ART) and using the etonogestrel implant have significantly
      lower systemic ENG concentrations than HIV-infected women not on ART. This finding has raised
      concerns regarding the contraceptive efficacy of the ENG implant for women on EFV-based ART
      and clinical studies have an increased rate of pregnancies for women on EFV-based ART and
      using a contraceptive implant. This study a randomized, open-label, longitudinal
      pharmacodynamic study to compare frequency of ovulation between a control group of
      HIV-infected women on efavirenz-based antiretroviral therapy receiving standard dose
      etonogestrel (ENG) implant and a treatment group receiving increased dose ENG implant. The
      overall goal is to assess the pharmacodynamic significance of the known drug-drug interaction
      between EFV and ENG and to determine if the increased dose will overcome this interaction.
      Overall, this study will improve long-acting reversible contraceptive treatment options for
      women living with HIV and prevent unintended pregnancy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Ovulation
time frame: weekly at months 3, 6, and 12
description: Ovulation evaluated by endogenous progesterone concentrations of >3ng/mL
measure: Cervical mucus quality
time frame: weekly at months 3, 6, and 12
description: World Health Organization Cervical Mucus Scores
measure: Etonogestrel pharmacokinetics
time frame: Week 1, 4, 12, 24, 36, and 48
description: Etonogestrel serum concentrations
measure: Adverse events
time frame: up to months 12
description: Safety
arm group label: Standard Dose Etonogestrel Implant
arm group type: Active Comparator
description: Single 68 mg etonogestrel implant
arm group label: Increased Dose Etonogestrel Implant
arm group type: Experimental
description: Two 68 mg (136 mg total) etonogestrel implants
intervention type: Drug
intervention name: etonogestrel implant
description: The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
arm group label: Increased Dose Etonogestrel Implant
arm group label: Standard Dose Etonogestrel Implant
other name: Nexplanon
other name: Implanon
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
facility: 
country: Uganda
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Catherine Anne Chappell
investigator title: Assistant Professor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Etonogestrel
sharing ipd: No