<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/NCT03032510</url>
  </required_header>
  <id_info>
    <org_study_id>TP-434-021</org_study_id>
    <nct_id>NCT03032510</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections</brief_title>
  <acronym>IGNITE3</acronym>
  <official_title>A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of IV Eravacycline Compared With Ertapenem in Complicated Urinary Tract Infections</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tetraphase Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>La Jolla Pharmaceutical Company</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of&#xD;
      eravacycline compared to ertapenem in treating participants with complicated urinary tract&#xD;
      infections (cUTI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of&#xD;
      eravacycline compared to ertapenem in treating participants with complicated urinary tract&#xD;
      infections (cUTI).&#xD;
&#xD;
      This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to&#xD;
      assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in&#xD;
      the treatment of cUTI.&#xD;
&#xD;
      Randomization will be stratified based on two criteria: (1) by primary site of infection&#xD;
      (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the&#xD;
      receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72&#xD;
      hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects&#xD;
      with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of&#xD;
      approximately 20% is planned for subjects who have received a single dose of non-study&#xD;
      antibiotics for the acute cUTI within 72 hours prior to randomization.&#xD;
&#xD;
      In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1&#xD;
      ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) /&#xD;
      levofloxacin (PO).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit</measure>
    <time_frame>End of Infusion</time_frame>
    <description>This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to &lt;10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit</measure>
    <time_frame>TOC visit (14-17 days after randomization)</time_frame>
    <description>This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to &lt;10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit</measure>
    <time_frame>TOC visit (14-17 days after randomization)</time_frame>
    <description>Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry.&#xD;
Clinical failure: Subjects were classified as clinical failure in the event of&#xD;
Death related to cUTI at any timepoint&#xD;
Persistence of clinical symptoms of cUTI or new symptoms developed&#xD;
Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1205</enrollment>
  <condition>Complicated Urinary Tract Infections</condition>
  <arm_group>
    <arm_group_label>Eravacycline (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Ertapenem (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eravacycline</intervention_name>
    <arm_group_label>Eravacycline (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <other_name>TP-434</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ertapenem</intervention_name>
    <arm_group_label>Ertapenem (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <other_name>Invanz</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Eravacycline (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <arm_group_label>Ertapenem (Intravenous)/Levofloxacin (Oral)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levofloxacin</intervention_name>
    <arm_group_label>Eravacycline (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <arm_group_label>Ertapenem (Intravenous)/Levofloxacin (Oral)</arm_group_label>
    <other_name>Levaquin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female participant with either:&#xD;
&#xD;
               1. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total&#xD;
                  population), or&#xD;
&#xD;
               2. cUTI with at least one of the following conditions associated with a risk for&#xD;
                  developing cUTI:&#xD;
&#xD;
                    -  Indwelling urinary catheter&#xD;
&#xD;
                    -  Urinary retention (at least approximately 100 milliliters (mL) of residual&#xD;
                       urine after voiding)&#xD;
&#xD;
                    -  History of neurogenic bladder&#xD;
&#xD;
                    -  Partial obstructive uropathy (for example, nephrolithiasis, bladder stones,&#xD;
                       and ureteral strictures)&#xD;
&#xD;
                    -  Azotemia of renal origin (not congestive heart failure [CHF] or volume&#xD;
                       related) such that the serum blood urea nitrogen [BUN] is elevated (&gt;20&#xD;
                       milligrams [mg]/deciliters [dL]) and the serum BUN:creatinine ratio is &lt;15&#xD;
&#xD;
                    -  Surgically modified or abnormal urinary tract anatomy (for example, bladder&#xD;
                       diverticula, redundant urine collection system) except urinary tract surgery&#xD;
                       within the last 30 days (placing of stents or catheters is not considered to&#xD;
                       be surgical modification)&#xD;
&#xD;
          2. At least 18 years of age at time of consent&#xD;
&#xD;
          3. Able to provide informed consent&#xD;
&#xD;
          4. At least two of the following signs or symptoms:&#xD;
&#xD;
               1. Chills, rigors, or warmth associated with fever or hypothermia&#xD;
&#xD;
               2. Flank pain (pyelonephritis) or pelvic pain (cUTI)&#xD;
&#xD;
               3. Nausea or vomiting&#xD;
&#xD;
               4. Dysuria, urinary frequency, or urinary urgency&#xD;
&#xD;
               5. Costo-vertebral angle tenderness on physical examination&#xD;
&#xD;
          5. Urine specimen with evidence of pyuria&#xD;
&#xD;
               1. Dipstick analysis positive for leukocyte esterase (where positive result is at&#xD;
                  least &quot;++&quot; as indicated on the urine dipstick provided in the laboratory kit), or&#xD;
&#xD;
               2. ≥10 white blood cells (WBCs) per cubic millimeter, or&#xD;
&#xD;
               3. ≥10 WBCs per high power field&#xD;
&#xD;
          6. If male: must agree to use an effective barrier method of contraception (for example,&#xD;
             condom) during the study and for 14 days following the last dose if sexually active&#xD;
             with a female of childbearing potential&#xD;
&#xD;
          7. If female, not pregnant or nursing or, if of childbearing potential: must commit to&#xD;
             either use at least two medically accepted, effective methods of birth control (for&#xD;
             example, condom, spermicidal gel, oral contraceptive, indwelling intrauterine device,&#xD;
             hormonal implant /patch, injections, approved cervical ring) during study drug dosing&#xD;
             and for 14 days following last study drug dose or practicing sexual abstinence&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment&#xD;
             except under the following circumstances:&#xD;
&#xD;
               1. Participants with suspected acute cUTI who have received a single dose of&#xD;
                  effective non-study antibiotics for the acute cUTI&#xD;
&#xD;
               2. Signs and symptoms of cUTI developed while on the antibiotic for another&#xD;
                  indication&#xD;
&#xD;
          2. History of an ertapenem-resistant urinary tract infection within 1 year of enrollment&#xD;
&#xD;
          3. Likely to require &gt;10 days of antibiotic treatment to cure the acute cUTI or likely to&#xD;
             receive ongoing antibacterial drug prophylaxis prior to the Follow Up visit (21-28&#xD;
             days after randomization) [for example, participants with chronic vesiculo-ureteral&#xD;
             reflux]&#xD;
&#xD;
          4. Unlikely to survive at least through the duration of the study&#xD;
&#xD;
          5. Hypotension, systolic blood pressure ≤90 millimeters of mercury [mmHg]&#xD;
&#xD;
          6. Complicated pyelonephritis with complete obstruction or known or suspected renal or&#xD;
             perinephric abscess, emphysematous pyelonephritis, or Any condition likely to require&#xD;
             surgery to achieve cure (this does not include procedure to place catheters or obtain&#xD;
             diagnosis)&#xD;
&#xD;
          7. Known or suspected urinary fungal infection&#xD;
&#xD;
          8. Uncomplicated lower urinary tract infections&#xD;
&#xD;
          9. Suspected or confirmed active prostatitis, or currently under treatment for&#xD;
             prostatitis&#xD;
&#xD;
         10. High risk for cUTI due to Pseudomonas (for example, history of prior cUTIs due to&#xD;
             Pseudomonas, ≥20 mg once a day prednisone or equivalent steroid, and other risk&#xD;
             factors as perceived by the Investigator)&#xD;
&#xD;
         11. History of renal transplantation&#xD;
&#xD;
         12. Presence of an ileal loop&#xD;
&#xD;
         13. Any history of trauma to the pelvis or urinary tract occurring within 30 days of&#xD;
             screening&#xD;
&#xD;
         14. Indwelling urinary catheters present at screening which are not expected to be removed&#xD;
             or replaced within 72 hours of enrollment (for example, nephrostomy tubes, stents,&#xD;
             urethral and suprapubic catheters).&#xD;
&#xD;
         15. Known concomitant human immunodeficiency virus (HIV) infection with CD4 counts below&#xD;
             200 within the last six months, or an acquired immune deficiency syndrome (AIDS)&#xD;
             defining diagnosis within the last six months&#xD;
&#xD;
         16. Neutropenia (Absolute neutrophil count &lt;1,000 polymorphonuclear leukocytes&#xD;
             [PMNs]/microliters [µL])&#xD;
&#xD;
         17. Participation in a study with an experimental drug or device within 30 days prior to&#xD;
             enrollment&#xD;
&#xD;
         18. Known or suspected hypersensitivity to tetracyclines, carbapenems, or β-lactams&#xD;
&#xD;
         19. History of seizures&#xD;
&#xD;
         20. Any other unstable or clinically significant concurrent medical condition (for&#xD;
             example, immunosuppressive therapy, chemotherapy, class IV heart or lung disease, end&#xD;
             stage renal disease, or requiring hemodialysis) that would, in the opinion of the&#xD;
             Investigator, jeopardize the safety of a participant and/or their compliance with the&#xD;
             protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chief Medical Officer</last_name>
    <role>Study Director</role>
    <affiliation>Tetraphase Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Doral</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Columbus</city>
        <state>Georgia</state>
        <zip>31820</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baytown</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Graz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Linz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salzburg</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pleven</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plovdiv</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Razgrad</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ruse</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Smyadovo</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Varna</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Veliko Tarnovo</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tallinn</city>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tartu</city>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Voru</city>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>K'ut'aisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>T'bilisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baja</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miskolc</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nagykanizsa</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nyiregyhaza</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sopron</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Szentes</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tatabanya</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jelgava</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Riga</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valmiera</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chisinau</city>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Braşov</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bucharest</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Craiova</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oradea</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Arkhangel'sk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pyatigorsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rostov-on-the-Don</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Smolensk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vsevolozhsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Yaroslavl'</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nitra</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poprad</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Presov</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Svidnik</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zilina</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chernihiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chernivtsi</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dnipro</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ivano-Frankivsk</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>L'viv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lviv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mykolaiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Odesa</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poltava</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Uzhgorod</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Uzhorod</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vinnytsya</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zaporizhia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zhytomyr</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Bulgaria</country>
    <country>Estonia</country>
    <country>Georgia</country>
    <country>Hungary</country>
    <country>Latvia</country>
    <country>Moldova, Republic of</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Slovakia</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <results_first_submitted>July 12, 2019</results_first_submitted>
  <results_first_submitted_qc>September 9, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 2, 2019</results_first_posted>
  <last_update_submitted>December 16, 2021</last_update_submitted>
  <last_update_submitted_qc>December 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Urinary Tract Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levofloxacin</mesh_term>
    <mesh_term>Ertapenem</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT03032510/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 22, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT03032510/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Eravacycline (Intravenous)/Levofloxacin (Oral)</title>
          <description>Eravacycline 1.5mg/kg IV q24h&#xD;
Placebo IV q24h&#xD;
Levofloxacin (PO)</description>
        </group>
        <group group_id="P2">
          <title>Ertapenem (Intravenous)/Levofloxacin (Oral)</title>
          <description>Ertapenem 1g IV q24h&#xD;
Placebo IV q24h&#xD;
Levofloxacin (PO)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="603"/>
                <participants group_id="P2" count="602"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="576"/>
                <participants group_id="P2" count="584"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject noncompliance</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Eravacycline (Intravenous)/Levofloxacin (Oral)</title>
          <description>Eravacycline 1.5 mg/kg IV q24h&#xD;
Placebo IV&#xD;
Levofloxacin PO</description>
        </group>
        <group group_id="B2">
          <title>Ertapenem (Intravenous)/Levofloxacin (Oral)</title>
          <description>Ertapenem 1.0g IV q24h&#xD;
Placebo IV&#xD;
Levofloxacin PO</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="603"/>
            <count group_id="B2" value="602"/>
            <count group_id="B3" value="1205"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="338"/>
                    <measurement group_id="B2" value="331"/>
                    <measurement group_id="B3" value="669"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="265"/>
                    <measurement group_id="B2" value="271"/>
                    <measurement group_id="B3" value="536"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="57.1" spread="18.16"/>
                    <measurement group_id="B2" value="56.5" spread="19.34"/>
                    <measurement group_id="B3" value="56.8" spread="18.7"/>
                  </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="330"/>
                    <measurement group_id="B2" value="343"/>
                    <measurement group_id="B3" value="673"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="273"/>
                    <measurement group_id="B2" value="259"/>
                    <measurement group_id="B3" value="532"/>
                  </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="11"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="592"/>
                    <measurement group_id="B2" value="587"/>
                    <measurement group_id="B3" value="1179"/>
                  </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_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_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_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="600"/>
                    <measurement group_id="B2" value="601"/>
                    <measurement group_id="B3" value="1201"/>
                  </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_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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Latvia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Austria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Romania</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hungary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ukraine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="148"/>
                    <measurement group_id="B2" value="137"/>
                    <measurement group_id="B3" value="285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Georgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Slovakia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bulgaria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Estonia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="126"/>
                    <measurement group_id="B2" value="143"/>
                    <measurement group_id="B3" value="269"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moldova</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit</title>
        <description>This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to &lt;10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.</description>
        <time_frame>End of Infusion</time_frame>
        <population>micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.</population>
        <group_list>
          <group group_id="O1">
            <title>Eravacycline (Intravenous)</title>
            <description>Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.</description>
          </group>
          <group group_id="O2">
            <title>Ertapenem (Intravenous)</title>
            <description>Ertapenem was administered IV at a dose of 1 g q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit</title>
          <description>This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to &lt;10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.</description>
          <population>micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="428"/>
                <count group_id="O2" value="403"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Responder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="363"/>
                    <measurement group_id="O2" value="382"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Indeterminate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit</title>
        <description>This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to &lt;10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.</description>
        <time_frame>TOC visit (14-17 days after randomization)</time_frame>
        <population>micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.</population>
        <group_list>
          <group group_id="O1">
            <title>Eravacycline</title>
            <description>micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.</description>
          </group>
          <group group_id="O2">
            <title>Ertapenem</title>
            <description>micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit</title>
          <description>This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to &lt;10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.</description>
          <population>micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="428"/>
                <count group_id="O2" value="403"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Responder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="293"/>
                    <measurement group_id="O2" value="302"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="116"/>
                    <measurement group_id="O2" value="86"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Indeterminate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit</title>
        <description>Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry.&#xD;
Clinical failure: Subjects were classified as clinical failure in the event of&#xD;
Death related to cUTI at any timepoint&#xD;
Persistence of clinical symptoms of cUTI or new symptoms developed&#xD;
Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.</description>
        <time_frame>TOC visit (14-17 days after randomization)</time_frame>
        <population>ITT included all randomized participants, regardless of receiving study drug or not.</population>
        <group_list>
          <group group_id="O1">
            <title>Eravacycline (Intravenous)/Levofloxacin (Oral)</title>
            <description>ITT included all randomized participants, regardless of receiving study drug or not.</description>
          </group>
          <group group_id="O2">
            <title>Ertapenem (Intravenous)/Levofloxacin (Oral)</title>
            <description>ITT included all randomized participants, regardless of receiving study drug or not.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit</title>
          <description>Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry.&#xD;
Clinical failure: Subjects were classified as clinical failure in the event of&#xD;
Death related to cUTI at any timepoint&#xD;
Persistence of clinical symptoms of cUTI or new symptoms developed&#xD;
Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.</description>
          <population>ITT included all randomized participants, regardless of receiving study drug or not.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="603"/>
                <count group_id="O2" value="602"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Clinical Cure</title>
                  <measurement_list>
                    <measurement group_id="O1" value="547"/>
                    <measurement group_id="O2" value="566"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clinical Failure</title>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Indeterminate/missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The time frame for adverse event reporting was from the first dose of study drug through 30 days after the last dose of study drug or the FU visit (whichever was later).</time_frame>
      <desc>The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.</desc>
      <group_list>
        <group group_id="E1">
          <title>Eravacycline (Intravenous)</title>
          <description>Eravacycline 1.5 mg/kg IV -The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.</description>
        </group>
        <group group_id="E2">
          <title>Ertapenem (Intravenous)</title>
          <description>Ertapenem 1 g IV-The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDra Version 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Cardiorenal syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Renal abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Meningioma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aneurysm ruptured</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Circulatory collapse</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDra Version 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="174" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="52" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="84" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion site phlebitis</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="600"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="601"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="600"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Development Officer</name_or_title>
      <organization>La Jolla Pharmaceutical Company</organization>
      <phone>617-715-3600</phone>
      <email>ljpcregulatory@ljpc.com</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/NCT03032510
org study id: TP-434-021
nct id: NCT03032510
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of
      eravacycline compared to ertapenem in treating participants with complicated urinary tract
      infections (cUTI).
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of
      eravacycline compared to ertapenem in treating participants with complicated urinary tract
      infections (cUTI).

      This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to
      assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in
      the treatment of cUTI.

      Randomization will be stratified based on two criteria: (1) by primary site of infection
      (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the
      receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72
      hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects
      with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of
      approximately 20% is planned for subjects who have received a single dose of non-study
      antibiotics for the acute cUTI within 72 hours prior to randomization.

      In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1
      ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) /
      levofloxacin (PO).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit
time frame: End of Infusion
description: This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
measure: Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit
time frame: TOC visit (14-17 days after randomization)
description: This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
measure: Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit
time frame: TOC visit (14-17 days after randomization)
description: Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry.
Clinical failure: Subjects were classified as clinical failure in the event of
Death related to cUTI at any timepoint
Persistence of clinical symptoms of cUTI or new symptoms developed
Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.
arm group label: Eravacycline (Intravenous)/Levofloxacin (Oral)
arm group type: Experimental
arm group label: Ertapenem (Intravenous)/Levofloxacin (Oral)
arm group type: Active Comparator
intervention type: Drug
intervention name: Eravacycline
arm group label: Eravacycline (Intravenous)/Levofloxacin (Oral)
other name: TP-434
intervention type: Drug
intervention name: Ertapenem
arm group label: Ertapenem (Intravenous)/Levofloxacin (Oral)
other name: Invanz
intervention type: Drug
intervention name: Placebo
arm group label: Eravacycline (Intravenous)/Levofloxacin (Oral)
arm group label: Ertapenem (Intravenous)/Levofloxacin (Oral)
intervention type: Drug
intervention name: Levofloxacin
arm group label: Eravacycline (Intravenous)/Levofloxacin (Oral)
arm group label: Ertapenem (Intravenous)/Levofloxacin (Oral)
other name: Levaquin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chief Medical Officer
role: Study Director
affiliation: Tetraphase Pharmaceuticals
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country: Austria
country: Bulgaria
country: Estonia
country: Georgia
country: Hungary
country: Latvia
country: Moldova, Republic of
country: Romania
country: Russian Federation
country: Slovakia
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Urinary Tract Infections
mesh term: Levofloxacin
mesh term: Ertapenem
sharing ipd: No
provided document: 
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participant flow: 
baseline: 
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certain agreements: 
point of contact: 