<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/NCT02236026</url>
  </required_header>
  <id_info>
    <org_study_id>648</org_study_id>
    <nct_id>NCT02236026</nct_id>
  </id_info>
  <brief_title>A Study With an Open-Label Active Control to Evaluate the Potential of Nestorone® to Delay Cardiac Repolarization in Healthy Female Volunteers</brief_title>
  <official_title>A Double-Blind, Placebo-Controlled, Randomized, Crossover Design Study With an Open-Label Active Control to Evaluate the Potential of Nestorone® to Delay Cardiac Repolarization in Healthy Female Volunteers: A Thorough QT/QTc Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Population Council</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Population Council</source>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the effect of Nestorone (NES) administered as an&#xD;
      bolus injection on the corrected QT interval using Fridericia's formula (QTcF).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the effect of Nestorone (NES) administered as an IV solution on the corrected QT interval using Fridericia's formula (QTcF).</measure>
    <time_frame>Days 1, 2, 30, 31, 32, and 33</time_frame>
    <description>Measurement of any changes from baseline in heart rhythm using an electrocardiogram at different time points after receiving NES as an IV solution</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Supratherapeutic dose of Nestorone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxifloxacin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Supratherapuetic dose of Nestorone</intervention_name>
    <arm_group_label>Supratherapeutic dose of Nestorone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <arm_group_label>Moxifloxacin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is a premenopausal female, ≥ 18 to &lt; 40 years of age at the time of Screening;&#xD;
&#xD;
          -  Has a BMI ≥ 18.5 and ≤ 32 kg/m2 (weight ≥ 50 kg) at Screening&#xD;
&#xD;
          -  Is in a state of general good health based on medical history and physical&#xD;
             examination;&#xD;
&#xD;
          -  Is regularly menstruating (cycles of 22 to 35 days duration) over the previous 6&#xD;
             months prior to Screening, as reported by the subject;&#xD;
&#xD;
          -  If of childbearing potential, must be practicing an acceptable non-hormonal, method of&#xD;
             birth control until the end of the study (Exit/Early Termination). Such methods&#xD;
             include but are not limited to: Sexual abstinence; Male or female condom in&#xD;
             combination with spermicidal foam/gel/cream/ suppository; Vasectomized or female&#xD;
             partner; Diaphragm/cervical cap with spermicide; Bilateral tubal ligation&#xD;
             sterilization at least 6 months before the screening visit, or an ESSURE or ADIANA&#xD;
             procedure with an hysterosalpingography confirmation test at least 6 months before the&#xD;
             screening visit; Copper intrauterine device.&#xD;
&#xD;
          -  Is able to fulfill the requirements of the protocol, and indicates a willingness to&#xD;
             participate in the study by providing written informed consent and an authorization to&#xD;
             disclose PHI.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is pregnant or lactating;&#xD;
&#xD;
          -  Has hypersensitivity or allergy to NES, moxifloxacin, or related compounds, or any of&#xD;
             the inactive ingredients used in the investigational product formulations;&#xD;
&#xD;
          -  Has a contraindication to progestin or estrogen therapy;&#xD;
&#xD;
          -  Has impaired hypothalamic-pituitary-adrenal reserve, or history of oral glucocorticoid&#xD;
             replacement therapy in 12 months prior to Screening.&#xD;
&#xD;
          -  Has experienced undiagnosed genital bleeding, excluding inter-menstrual spotting,&#xD;
             within 6 months of Screening;&#xD;
&#xD;
          -  Has undergone a gynecological examination, which results in clinically significant&#xD;
             abnormalities, at Screening;&#xD;
&#xD;
          -  Has had treatment with oral, topical or vaginal steroid hormones (e.g., estrogens,&#xD;
             progestogens, androgens [including dehydroepiandrosterone], corticosteroids) within 8&#xD;
             weeks prior to Screening, or treatment with injectable or implantable steroids at any&#xD;
             time during the 6 months prior to Screening;&#xD;
&#xD;
          -  Is currently using, or has used within 6 months prior to Screening, hormonal&#xD;
             contraception or progestin intrauterine device.&#xD;
&#xD;
          -  Has known or suspected carcinoma of the breast;&#xD;
&#xD;
          -  Has benign or malignant liver tumors or acute liver disease;&#xD;
&#xD;
          -  Has current or past thrombophlebitis or thromboembolic disorders or a family history&#xD;
             of thromboembolic disorders;&#xD;
&#xD;
          -  Has a personal history of myocardial disease, Long QT Syndrome or a personal or family&#xD;
             history of Long QT Syndrome (e.g., Anderson-Tawil Syndrome [micrognathia, low set&#xD;
             ears, clinodactyly]; Timothy's Syndrome [syndactyly and autism spectrum disorder];:&#xD;
             Jervell/Lange-Nielsen Syndrome [bilateral hearing loss]; Romano-Ward Syndrome&#xD;
             [fainting, seizures]), unexplained syncope or presyncope, or current or recurrent&#xD;
             hypokalemia.&#xD;
&#xD;
          -  Has a family history in genetically related grandparents, parents, uncles/aunts,&#xD;
             cousins, or children of Long QT Syndrome, non-ischemic cardiomyopathy, or unexplained&#xD;
             sudden death before 50 years of age.&#xD;
&#xD;
          -  Has an abnormal 12-lead ECG, with clinically significant abnormalities of rate,&#xD;
             rhythm, or conduction including: HR &lt; 45 or &gt; 90 beats per minute (bpm), after a 5&#xD;
             minute supine rest; PR interval &gt; 220 ms; QRS interval &gt; 120 ms; QTcF or corrected QT&#xD;
             interval using Bazett's formula (to be determined by Investigator) &gt; 450 ms; QTcF &lt;&#xD;
             300 ms; Any degree of clinically significant fascicular block, bundle branch block, or&#xD;
             intraventricular conduction delay; QRS and/or T wave that the Investigator judges to&#xD;
             be unfavorable for consistently accurate QT measurements (e.g., indistinct QRS onset,&#xD;
             low amplitude T wave, inverted or terminally inverted T wave, merged T/U waves,&#xD;
             indistinct T wave offset, or prominent U wave that affects QT measurement);&#xD;
             Neuromuscular artifact that cannot be readily eliminated;&#xD;
&#xD;
          -  Has, on ECG, premature atrial or ventricular beats or other findings that in the&#xD;
             Investigator's opinion represent clinically significant excessive HR variation;&#xD;
&#xD;
          -  Has any clinically significant deviation from normal in any of the screening tests or&#xD;
             initial exams that, in the opinion of the Investigator, might present a safety risk&#xD;
             for participation or would confound analysis or interpretation of the study results;&#xD;
&#xD;
          -  Has participated in a clinical study or used any investigational drug within the 60&#xD;
             days prior to Screening;&#xD;
&#xD;
          -  Requires the use of medication, including over-the-counter products, or nutritional&#xD;
             supplements, with the exception of aspirin, ibuprofen, and acetaminophen. Medications&#xD;
             are not exclusionary if they are discontinued as described below; however, under no&#xD;
             circumstance should medication be discontinued if doing so would place a subject at&#xD;
             risk; Medications (including nutritional supplements) known to be moderate or potent&#xD;
             inhibitor of cytochrome P450 (CYP) 3A4, or to prolong the QT/QTc interval, must be&#xD;
             discontinued at least 21 days prior to study entry (Day -1 of Treatment Period 1); All&#xD;
             other prescription medications must be discontinued at least 14 days prior to study&#xD;
             entry (Day -1 of Treatment Period 1), unless in the opinion of the Investigator the&#xD;
             concomitant use of such medication does not place the subject at risk and will not&#xD;
             confound the collection, analysis, or interpretation of study data; Over-the-counter&#xD;
             medications (including nutritional supplements) must be discontinued at least 7 days&#xD;
             prior to study entry (Day -1 of Treatment Period 1);&#xD;
&#xD;
          -  Foods or beverages containing alcohol, caffeine, xanthine, or grapefruit are not&#xD;
             allowed within 48 hours of Day -1 of each treatment period.&#xD;
&#xD;
          -  Has a positive hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) screen;&#xD;
&#xD;
          -  Has a positive test for alcohol or drugs of abuse, or a history of known or suspected&#xD;
             alcohol or drug abuse;&#xD;
&#xD;
          -  Has used tobacco products within 6 months prior to Screening, or has a positive urine&#xD;
             test for tobacco use;&#xD;
&#xD;
          -  Has donated more than 400 mL of blood/plasma in the 60 days prior to Day -1 of&#xD;
             Treatment Period 1;&#xD;
&#xD;
          -  Is unable or unwilling to provide written informed consent or comply with the&#xD;
             activities or instructions of the study;&#xD;
&#xD;
          -  Is judged by the Investigator to be unsuitable for any reason.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>George W. Creasy, MD</last_name>
    <role>Study Director</role>
    <affiliation>Population Council</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Harbor Hospital, 3001 South Hanover Street, 7th Floor</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>August 11, 2017</last_update_submitted>
  <last_update_submitted_qc>August 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nestorone use as an IV solution on heart rate;</keyword>
  <keyword>Abnormality in Heart Rate or Rhythm, Unspecified as to Time of Onset</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>ST 1435</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02236026
org study id: 648
nct id: NCT02236026
lead sponsor: 
collaborator: 
The purpose of the study is to evaluate the effect of Nestorone (NES) administered as an
      bolus injection on the corrected QT interval using Fridericia's formula (QTcF).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: To evaluate the effect of Nestorone (NES) administered as an IV solution on the corrected QT interval using Fridericia's formula (QTcF).
time frame: Days 1, 2, 30, 31, 32, and 33
description: Measurement of any changes from baseline in heart rhythm using an electrocardiogram at different time points after receiving NES as an IV solution
arm group label: Supratherapeutic dose of Nestorone
arm group type: Experimental
description: Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor
arm group label: Moxifloxacin
arm group type: Experimental
description: Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor
intervention type: Drug
intervention name: Supratherapuetic dose of Nestorone
arm group label: Supratherapeutic dose of Nestorone
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Moxifloxacin
arm group label: Moxifloxacin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: George W. Creasy, MD
role: Study Director
affiliation: Population Council
facility: 
country: United States
responsible party type: Sponsor
mesh term: Moxifloxacin
mesh term: ST 1435