<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/NCT03840811</url>
  </required_header>
  <id_info>
    <org_study_id>09-0106</org_study_id>
    <nct_id>NCT03840811</nct_id>
  </id_info>
  <brief_title>Experimental Human Infection With Neisseria Gonorrhoeae</brief_title>
  <official_title>Experimental Human Infection With Isogenic Mutants of Neisseria Gonorrhoeae</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</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 is a Phase 1, interventional, non-randomized, experimental infection model study with&#xD;
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is&#xD;
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for&#xD;
      gonococcal infection in the male urethra. The duration for all participants will be about 3&#xD;
      weeks. Study duration will be approximately about 18 months for implementation and&#xD;
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of&#xD;
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections&#xD;
      and to (2) assess relative fitness of the mutant in competitive infections initiated by&#xD;
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT&#xD;
      infectivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, interventional, non-randomized, experimental infection model study with&#xD;
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is&#xD;
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for&#xD;
      gonococcal infection in the male urethra. For each mutant to be investigated under this&#xD;
      protocol, groups of subjects will be enrolled first in noncompetitive infection studies:&#xD;
      Group 1 (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant&#xD;
      N. gonorrhoeae strain, and Group 2 (n = up to 8) will receive a bacterial inoculum containing&#xD;
      only the wild-type (WT) N. gonorrhoeae strain. If primary and secondary outcomes are not&#xD;
      different for the isogenic mutant and WT strains, a group of subjects will be enrolled in&#xD;
      competitive infection studies: Group 3 (up to 16) will receive a bacterial inoculum&#xD;
      containing a mixture of equivalent numbers the isogenic mutant and WT strain. All subjects&#xD;
      will be examined daily for symptoms of infection and receive antibiotic treatment at the end&#xD;
      of the inpatient portion of the trial. Within 7 days of antibiotic treatment, subjects will&#xD;
      return for a follow-up examination. A final follow-up phone interview will be conducted&#xD;
      within 2 weeks of antibiotic treatment. The duration for all participants will be about 3&#xD;
      weeks. Study duration will be approximately about 18 months for implementation and&#xD;
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of&#xD;
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections&#xD;
      and to (2) assess relative fitness of the mutant in competitive infections initiated by&#xD;
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT&#xD;
      infectivity. Note, competitive infections will not be performed if non-competitive infections&#xD;
      are substantially different. If this is the case, there will be no analysis for this primary&#xD;
      objective. The study secondary objective is to compare the clinical course of infection with&#xD;
      mutant and WT N. gonorrhoeae in noncompetitive infections.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 23, 2017</start_date>
  <completion_date type="Actual">November 25, 2019</completion_date>
  <primary_completion_date type="Actual">November 25, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants</measure>
    <time_frame>Baseline and the day of treatment, any day between Day 2 and Day 6</time_frame>
    <description>The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input):&#xD;
CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input).&#xD;
The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index.&#xD;
The assessment was performed in the MtrD trial mixed group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections</measure>
    <time_frame>day of infection, any day between Day 2 and Day 6</time_frame>
    <description>Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 6.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula</measure>
    <time_frame>day of infection, any day between Day 2 and Day 6</time_frame>
    <description>Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula. Participants could become infected and received treatment any day before or on day 6.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections</measure>
    <time_frame>Day 2 through the day of treatment, up to Day 6</time_frame>
    <description>The median time from inoculation to antibiotic treatment were calculated for each group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain</measure>
    <time_frame>Day of occurrence, any day between Day 2 and Day 6</time_frame>
    <description>Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain</measure>
    <time_frame>Day of occurrence, any day between Day 2 and Day 6</time_frame>
    <description>Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections</measure>
    <time_frame>Day of occurrence, any day between Day 2 and Day 6</time_frame>
    <description>Urethritis is defined as &gt;= 5.8 Log10 WBC/mL urine sediment.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Gonococcal Infection</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects (n= up to 16) will receive a bacterial inoculum containing a mixture of equivalent numbers the isogenic mutant and WT strain</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cefixime</intervention_name>
    <description>Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceftriaxone</intervention_name>
    <description>Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ciprofloxacin</intervention_name>
    <description>Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positie test of cure 1 week post initial antibiotic treatment</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Neisseria gonorrhoeae strain FA1090 A26</intervention_name>
    <description>0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.</description>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Neisseria gonorrhoeae strain FA7537</intervention_name>
    <description>0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy man &gt; / = 18 and &lt; 36 years old&#xD;
&#xD;
          2. Able and willing to be located easily by providing street address and telephone number&#xD;
             (land line and/or cell phone number)&#xD;
&#xD;
          3. Willingness to provide written informed consent&#xD;
&#xD;
          4. Able and willing to attend all study visits including 6-day stay in the Clinical&#xD;
             Translational Research Center (CTRC) during the trial (with ability to leave the unit&#xD;
             during the day) and follow-up visit during the week after treatment&#xD;
&#xD;
          5. Able and willing to abstain from all sexual activity until completion of the study and&#xD;
             the follow-up test for gonorrhea is negative&#xD;
&#xD;
          6. Acceptable medical history by screening evaluation&#xD;
&#xD;
          7. No clinically significant abnormalities on physical exam&#xD;
&#xD;
          8. Urinalysis: leukocyte esterase, and White Blood Cell (WBC) values within normal limits&#xD;
             (WNL)&#xD;
&#xD;
          9. CH50 WNL&#xD;
&#xD;
         10. Urine negative for chlamydia, gonorrhea, and trichomonas&#xD;
&#xD;
         11. Negative Human Immunodeficiency Virus (HIV), syphilis, and Hepatitis C (HCV) test&#xD;
             results&#xD;
&#xD;
         12. Negative Hepatitis B (HBV) core and surface antibodies or results consistent with&#xD;
             immunization (negative HBV core antibody/positive HBV surface antibody)&#xD;
&#xD;
         13. Denies history of Sexually Transmitted Infections (STIs) including gonorrhea,&#xD;
             chlamydia, syphilis, HIV, HBV, and HCV&#xD;
&#xD;
         14. Denies history of bleeding diathesis&#xD;
&#xD;
         15. Denies history of seizures (due to reports of seizures with ciprofloxacin)&#xD;
&#xD;
         16. Denies history of cancer, except basal cell carcinoma of the skin &gt; 5 years ago&#xD;
&#xD;
         17. Denies history of drug abuse&#xD;
&#xD;
         18. Denies history of genitourinary surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Student or employee under the direct supervision of any of the study investigators&#xD;
&#xD;
          2. Any known immunodeficiencies including complement deficiency, antibody deficiency,&#xD;
             chronic granulomatous disease or Human Immunodeficiency Virus (HIV) infection&#xD;
&#xD;
          3. Psychiatric disorders that, in the opinion of the physician, would interfere with the&#xD;
             integrity of the data or volunteer safety&#xD;
&#xD;
          4. Unstable depression (defined as receiving either &lt; 3 months of the same medication&#xD;
             (and dose) or a decompensating event during the previous 3 months) or depression that,&#xD;
             in the opinion of the investigator, will compromise the subject's ability to comply&#xD;
             with protocol requirements&#xD;
&#xD;
          5. Heart murmur or heart disease&#xD;
&#xD;
          6. Anatomic abnormality of the urinary tract&#xD;
&#xD;
          7. Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days&#xD;
&#xD;
          8. Self-reported chemotherapy within the past year&#xD;
&#xD;
          9. Current steroid use, except for topical application&#xD;
&#xD;
         10. Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine&#xD;
&#xD;
         11. Treatment with medications in the previous month that are contraindicated with&#xD;
             cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single&#xD;
             doses given in this study&#xD;
&#xD;
         12. Serum creatinine level &lt; 0.7 or &gt; 1.75 mg/dL and deemed clinically significant by the&#xD;
             study physician&#xD;
&#xD;
         13. Serum ALT level &lt; LLN or &gt; 105 U/L and deemed clinically significant by the study&#xD;
             physician&#xD;
&#xD;
         14. WBC count &lt; 2.5 or &gt; 15.0 x 10^9/L and deemed clinically significant by the study&#xD;
             physician&#xD;
&#xD;
         15. Absolute neutrophil count (ANC) &lt; 1.5 or &gt; 7.5 x 10^9/L and deemed clinically&#xD;
             significant by the study physician Exception: For African Americans, ANC values as low&#xD;
             as 1.3 x 10^9/L will be allowed (25)&#xD;
&#xD;
         16. Hemoglobin level &lt; 12.0 g/dL or above ULN and deemed clinically significant by the&#xD;
             study physician&#xD;
&#xD;
         17. Urinalysis: Qualitative protein level &gt; 1+ or RBC count &gt; 10/hpf&#xD;
&#xD;
        Medications not permitted with cefixime or ceftriaxone:&#xD;
&#xD;
          1. Warfarin&#xD;
&#xD;
          2. Probenecid&#xD;
&#xD;
          3. Aspirin&#xD;
&#xD;
          4. Diuretics such as furosemide&#xD;
&#xD;
          5. Aminoglycoside antibiotics&#xD;
&#xD;
          6. Chloramphenicol&#xD;
&#xD;
        Medications not permitted with ciprofloxacin:&#xD;
&#xD;
          1. Tizanidine&#xD;
&#xD;
          2. Theophylline&#xD;
&#xD;
          3. Warfarin&#xD;
&#xD;
          4. Glyburide&#xD;
&#xD;
          5. Cyclosporine&#xD;
&#xD;
          6. Probenecid&#xD;
&#xD;
          7. Phenytoin&#xD;
&#xD;
          8. Methotrexate&#xD;
&#xD;
          9. Antacids, multivitamins, and other dietary supplements containing magnesium, calcium,&#xD;
             aluminum, iron or zinc&#xD;
&#xD;
         10. Caffeine-containing medications&#xD;
&#xD;
         11. Sucralfate or didanosine chewable or buffered tablets&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>36 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of North Carolina Health Care - Infectious Diseases</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514-4220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 16, 2020</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <results_first_submitted>November 12, 2020</results_first_submitted>
  <results_first_submitted_qc>February 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 23, 2021</results_first_posted>
  <last_update_submitted>February 26, 2021</last_update_submitted>
  <last_update_submitted_qc>February 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ceftriaxone</keyword>
  <keyword>challenge</keyword>
  <keyword>ciprofloxacin</keyword>
  <keyword>males</keyword>
  <keyword>Neisseria gonorrhoeae</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Gonorrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciprofloxacin</mesh_term>
    <mesh_term>Ceftriaxone</mesh_term>
    <mesh_term>Cefixime</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03840811/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Males aged 18-&lt;36 years old, living in central North Carolina, in general good health with no history of sexually transmitted infection (STIs) were enrolled. Participants were enrolled between 23APR2017 and 10NOV2019.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Mutant FA7537</title>
          <description>Participants received a bacterial inoculum containing only the isogenic mtrD mutant N. gonorrhoeae strain.&#xD;
Cefixime: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.&#xD;
Ceftriaxone: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.&#xD;
Ciprofloxacin: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the participant has a positie test of cure 1 week post initial antibiotic treatment.&#xD;
Neisseria gonorrhoeae strain FA7537: 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.</description>
        </group>
        <group group_id="P2">
          <title>Wild-type FA1090</title>
          <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.&#xD;
Cefixime: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.&#xD;
Ceftriaxone: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.&#xD;
Ciprofloxacin: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the participant has a positie test of cure 1 week post initial antibiotic treatment.&#xD;
Neisseria gonorrhoeae strain FA1090 A26: 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.</description>
        </group>
        <group group_id="P3">
          <title>Mixed FA1090/FA7537</title>
          <description>Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.&#xD;
Cefixime: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.&#xD;
Ceftriaxone: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.&#xD;
Ciprofloxacin: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the participant has a positie test of cure 1 week post initial antibiotic treatment.&#xD;
Neisseria gonorrhoeae strain FA1090 A26: 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.&#xD;
Neisseria gonorrhoeae strain FA7537: 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <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_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline analysis population includes all enrolled participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Mutant FA7537</title>
          <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
        </group>
        <group group_id="B2">
          <title>Wild-type FA1090</title>
          <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
        </group>
        <group group_id="B3">
          <title>Mixed FA1090/FA7537</title>
          <description>Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.</description>
        </group>
        <group group_id="B4">
          <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="9"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.2" spread="6.1"/>
                    <measurement group_id="B2" value="21.8" spread="2.8"/>
                    <measurement group_id="B3" value="25.2" spread="4.7"/>
                    <measurement group_id="B4" value="24.4" spread="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants</title>
        <description>The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input):&#xD;
CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input).&#xD;
The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index.&#xD;
The assessment was performed in the MtrD trial mixed group.</description>
        <time_frame>Baseline and the day of treatment, any day between Day 2 and Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose, reached an objective study endpoint (urethral discharge or day 6), and had a valid competitive index (the competitive index could not be calculated for participant who had a negative urine culture result on the day of treatment).</population>
        <group_list>
          <group group_id="O1">
            <title>Mixed FA1090/FA7537</title>
            <description>Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.</description>
          </group>
        </group_list>
        <measure>
          <title>The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants</title>
          <description>The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input):&#xD;
CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input).&#xD;
The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index.&#xD;
The assessment was performed in the MtrD trial mixed group.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose, reached an objective study endpoint (urethral discharge or day 6), and had a valid competitive index (the competitive index could not be calculated for participant who had a negative urine culture result on the day of treatment).</population>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.11" lower_limit="0.01" upper_limit="78.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>To assess whether the fitness of a given mutant is different than that of wild-type, the ratio of colony-forming units of the mutant strain was compared to those of the WT strain at the time of treatment and in the inoculum using a Wilcoxon Signed-Rank Test with a significance level of 0.025. CIs of participants in Mixed FA1090 + FA7537 group were compared to mean = 1.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.230</p_value>
            <method>Sign test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections</title>
        <description>Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 6.</description>
        <time_frame>day of infection, any day between Day 2 and Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Mutant FA7537</title>
            <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
          </group>
          <group group_id="O2">
            <title>Wild-type FA1090</title>
            <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections</title>
          <description>Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 6.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.86" lower_limit="0.42" upper_limit="1.00"/>
                    <measurement group_id="O2" value="1.00" lower_limit="0.54" upper_limit="1.00"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.54</p_value>
            <p_value_desc>One-sided Fisher's Exact Test with alpha=0.025</p_value_desc>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>-0.14</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.58</ci_lower_limit>
            <ci_upper_limit>0.34</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula</title>
        <description>Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula. Participants could become infected and received treatment any day before or on day 6.</description>
        <time_frame>day of infection, any day between Day 2 and Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Mixed FA1090/FA7537</title>
            <description>Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula</title>
          <description>Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula. Participants could become infected and received treatment any day before or on day 6.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" lower_limit="0.72" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections</title>
        <description>The median time from inoculation to antibiotic treatment were calculated for each group.</description>
        <time_frame>Day 2 through the day of treatment, up to Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Mutant FA7537</title>
            <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
          </group>
          <group group_id="O2">
            <title>Wild-type FA1090</title>
            <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections</title>
          <description>The median time from inoculation to antibiotic treatment were calculated for each group.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="1" upper_limit="5"/>
                    <measurement group_id="O2" value="3.0" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain</title>
        <description>Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.</description>
        <time_frame>Day of occurrence, any day between Day 2 and Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Mutant FA7537</title>
            <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
          </group>
          <group group_id="O2">
            <title>Wild-type FA1090</title>
            <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain</title>
          <description>Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.86" lower_limit="0.42" upper_limit="1.00"/>
                    <measurement group_id="O2" value="1.00" lower_limit="0.54" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain</title>
        <description>Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.</description>
        <time_frame>Day of occurrence, any day between Day 2 and Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Mutant FA7537</title>
            <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
          </group>
          <group group_id="O2">
            <title>Wild-type FA1090</title>
            <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain</title>
          <description>Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" lower_limit="0.59" upper_limit="1.00"/>
                    <measurement group_id="O2" value="1.00" lower_limit="0.54" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections</title>
        <description>Urethritis is defined as &gt;= 5.8 Log10 WBC/mL urine sediment.</description>
        <time_frame>Day of occurrence, any day between Day 2 and Day 6</time_frame>
        <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Mutant FA7537</title>
            <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
          </group>
          <group group_id="O2">
            <title>Wild-type FA1090</title>
            <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections</title>
          <description>Urethritis is defined as &gt;= 5.8 Log10 WBC/mL urine sediment.</description>
          <population>The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" lower_limit="0.59" upper_limit="1.00"/>
                    <measurement group_id="O2" value="1.00" lower_limit="0.54" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events that occurred from inoculation (Day 1) through the 2 week final follow-up phone call (Study Days 12-23) were reported.</time_frame>
      <desc>The solicited and unsolicited AEs reported for the MtrD trial were summarized using MedDRA 22.1</desc>
      <group_list>
        <group group_id="E1">
          <title>Mutant FA7537</title>
          <description>Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.</description>
        </group>
        <group group_id="E2">
          <title>Wild-type FA1090</title>
          <description>Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.</description>
        </group>
        <group group_id="E3">
          <title>Mixed FA1090/FA7537</title>
          <description>Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.</description>
        </group>
      </group_list>
      <serious_events>
        <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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Non-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="9" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Feverishness</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal Allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Pressure Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Heart Rate Irregular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tingling</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urethral Discharge</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" events="13" subjects_affected="12" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary Frequency</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urethral Discharge</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urethritis Noninfective</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Irritation or Itching</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Testicular Pain</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marcia M. Hobbs, PhD</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>(919) 843-6893</phone>
      <email>mmhobbs@med.unc.edu</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/NCT03840811
org study id: 09-0106
nct id: NCT03840811
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a Phase 1, interventional, non-randomized, experimental infection model study with
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for
      gonococcal infection in the male urethra. The duration for all participants will be about 3
      weeks. Study duration will be approximately about 18 months for implementation and
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections
      and to (2) assess relative fitness of the mutant in competitive infections initiated by
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT
      infectivity.
This is a Phase 1, interventional, non-randomized, experimental infection model study with
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for
      gonococcal infection in the male urethra. For each mutant to be investigated under this
      protocol, groups of subjects will be enrolled first in noncompetitive infection studies:
      Group 1 (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant
      N. gonorrhoeae strain, and Group 2 (n = up to 8) will receive a bacterial inoculum containing
      only the wild-type (WT) N. gonorrhoeae strain. If primary and secondary outcomes are not
      different for the isogenic mutant and WT strains, a group of subjects will be enrolled in
      competitive infection studies: Group 3 (up to 16) will receive a bacterial inoculum
      containing a mixture of equivalent numbers the isogenic mutant and WT strain. All subjects
      will be examined daily for symptoms of infection and receive antibiotic treatment at the end
      of the inpatient portion of the trial. Within 7 days of antibiotic treatment, subjects will
      return for a follow-up examination. A final follow-up phone interview will be conducted
      within 2 weeks of antibiotic treatment. The duration for all participants will be about 3
      weeks. Study duration will be approximately about 18 months for implementation and
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections
      and to (2) assess relative fitness of the mutant in competitive infections initiated by
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT
      infectivity. Note, competitive infections will not be performed if non-competitive infections
      are substantially different. If this is the case, there will be no analysis for this primary
      objective. The study secondary objective is to compare the clinical course of infection with
      mutant and WT N. gonorrhoeae in noncompetitive infections.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants
time frame: Baseline and the day of treatment, any day between Day 2 and Day 6
description: The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input):
CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input).
The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index.
The assessment was performed in the MtrD trial mixed group.
measure: Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections
time frame: day of infection, any day between Day 2 and Day 6
description: Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 6.
measure: Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula
time frame: day of infection, any day between Day 2 and Day 6
description: Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula. Participants could become infected and received treatment any day before or on day 6.
measure: Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections
time frame: Day 2 through the day of treatment, up to Day 6
description: The median time from inoculation to antibiotic treatment were calculated for each group.
measure: Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain
time frame: Day of occurrence, any day between Day 2 and Day 6
description: Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.
measure: Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain
time frame: Day of occurrence, any day between Day 2 and Day 6
description: Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.
measure: Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections
time frame: Day of occurrence, any day between Day 2 and Day 6
description: Urethritis is defined as >= 5.8 Log10 WBC/mL urine sediment.
arm group label: Group 1
arm group type: Experimental
description: Subjects (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain
arm group label: Group 2
arm group type: Experimental
description: Subjects (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
arm group label: Group 3
arm group type: Experimental
description: Subjects (n= up to 16) will receive a bacterial inoculum containing a mixture of equivalent numbers the isogenic mutant and WT strain
intervention type: Drug
intervention name: Cefixime
description: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
intervention type: Drug
intervention name: Ceftriaxone
description: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
intervention type: Drug
intervention name: Ciprofloxacin
description: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positie test of cure 1 week post initial antibiotic treatment
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
intervention type: Biological
intervention name: Neisseria gonorrhoeae strain FA1090 A26
description: 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.
arm group label: Group 2
arm group label: Group 3
intervention type: Biological
intervention name: Neisseria gonorrhoeae strain FA7537
description: 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter
arm group label: Group 1
arm group label: Group 3
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 36 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Gonorrhea
mesh term: Ciprofloxacin
mesh term: Ceftriaxone
mesh term: Cefixime
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 