<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/NCT03234738</url>
  </required_header>
  <id_info>
    <org_study_id>TP-271-002</org_study_id>
    <secondary_id>HHSN272201100028C</secondary_id>
    <nct_id>NCT03234738</nct_id>
  </id_info>
  <brief_title>A Phase 1 Safety and PK Study of IV TP-271</brief_title>
  <official_title>A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Intravenous TP-271 in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tetraphase Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </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>
      This is a single-center, randomized, placebo-controlled, double-blind,&#xD;
      multiple-ascending-dose, inpatient study to assess the safety, tolerability, and&#xD;
      pharmacokinetics of TP-271 in healthy subjects. Subjects aged 18 to 50 years who fulfill the&#xD;
      inclusion/exclusion criteria will be enrolled in this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 5 cohorts of 8 subjects each (up to a total of 40 subjects) will be enrolled. The 8&#xD;
      subjects within each cohort will be randomized 6:2 to receive multiple IV doses of TP-271 or&#xD;
      placebo. Study drug will be administered IV once daily on the morning of Days 1 through 7&#xD;
      following an overnight fast (minimum 8 hours). The planned doses for study drug for Cohorts A&#xD;
      - E are 0.5 mg/kg TP-271 or placebo, 1.0 mg/kg TP-271 or placebo, 2.0 mg/kg TP-271 or&#xD;
      placebo, 2.5 mg/kg TP-271 or placebo and 3.0 mg/kg TP-271 or placebo respectively.&#xD;
&#xD;
      During the Screening period (Days -28 to -2 prior to the subject receiving TP-271 or&#xD;
      placebo), each subject will be assessed for eligibility. Each subject must sign and date the&#xD;
      ICF prior to undergoing any study-related procedures.&#xD;
&#xD;
      All cohorts will follow the same study design. On Day -1, subjects will be admitted to the&#xD;
      study unit and eligibility confirmed. On Day 1, eligible subjects will be enrolled and&#xD;
      randomized to receive either TP-271 or placebo and will receive the assigned drug from Days 1&#xD;
      through 7. Subjects will be required to stay at the study unit from Days -1 through 11 to&#xD;
      assess safety and obtain the required PK samples. On Day 11, subjects will be discharged from&#xD;
      the study unit. A final safety assessment will be performed once between Days 14 and 20, 7 to&#xD;
      13 days following administration of the subject's final dose of study drug.&#xD;
&#xD;
      After all 8 subjects in a cohort have completed study procedures through Day 11, the&#xD;
      Principal Investigator and the Sponsor's Medical Monitor will evaluate all blinded safety and&#xD;
      plasma PK data to determine whether any criteria that would require a meeting of the Safety&#xD;
      Monitoring Committee (SMC) are met. If no such criteria are met, the study may proceed to the&#xD;
      subsequent cohort at the next higher dose of TP-271 without consulting the SMC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 16, 2017</start_date>
  <completion_date type="Actual">January 2, 2018</completion_date>
  <primary_completion_date type="Actual">January 2, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Five Multiple-Ascending Doses</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>IV bags and lines are covered to prevent unblinding.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Throughout the study, ~ 49 days</time_frame>
    <description>Incidence, intensity, and type of adverse events (AEs) from the time of signing the informed consent form (ICF) through the EOS Visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical Exams</measure>
    <time_frame>~ 20 days</time_frame>
    <description>Changes in physical examination findings between Day -1 and the EOS Visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital Signs</measure>
    <time_frame>~ 20 days</time_frame>
    <description>Changes in vital signs from Day -1 through the EOS Visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety Laboratory Results</measure>
    <time_frame>~ 20 days</time_frame>
    <description>Changes in safety laboratory (clinical chemistry, electrolytes, hematology, blood glucose, and coagulation) results from Day -1 through the EOS Visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ECG measurements</measure>
    <time_frame>~ 20 days</time_frame>
    <description>Changes in electrocardiogram (ECG) measurements from Day -1 through the EOS Visit</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the Pharmacokinetics (PK) of TP-271in Plasma</measure>
    <time_frame>~11 days</time_frame>
    <description>Plasma concentrations of TP-271 and its C-4 epimer, TP-9555, for PK analysis from Days 1 through 11</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Pharmacokinetics (PK) of TP-271 in Urine</measure>
    <time_frame>~11 days</time_frame>
    <description>Urine concentrations of TP-271 and its C-4 epimer, TP-9555, from Days 1 through 11</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Bacterial Infections</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 0.5 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 1.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.5 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort E</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 3.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TP-271</intervention_name>
    <description>multiple oral doses of TP-271 or placebo, dosed once daily for 7 days, randomized 3:1, doses escalating as 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_label>Cohort E</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo is sterile 0.45% saline randomized 3:1 to receive</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_label>Cohort E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be within the age range of 18 to 50 years, inclusive, at the time of Screening&#xD;
&#xD;
          2. Voluntarily sign an Institutional Review Board (IRB)/Independent Ethics Committee&#xD;
             (IEC) approved ICF to participate in the study after all relevant aspects of the study&#xD;
             have been explained and discussed with the subject and before undergoing any&#xD;
             study-related procedures&#xD;
&#xD;
          3. Have a body mass index (BMI) ≥18.0 and ≤33.0 kg/m2&#xD;
&#xD;
          4. Have a negative history of and negative screening results for human immunodeficiency&#xD;
             virus 1 and 2 and hepatitis B and C antibodies&#xD;
&#xD;
          5. Have the ability to communicate with the study unit staff in a manner sufficient to&#xD;
             carry out all protocol procedures as described&#xD;
&#xD;
          6. For female subjects, be of non-childbearing potential, either 1 year postmenopausal or&#xD;
             surgically sterile (bilateral oophorectomy, bilateral tubal ligation, or complete&#xD;
             hysterectomy)&#xD;
&#xD;
          7. For male subjects, be willing and able to use a barrier method of contraception or&#xD;
             practice abstinence (including males who had a vasectomy) from dosing through 90 days&#xD;
             after administration of the final dose of study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History and/or presence of any clinically significant disease or disorder such as&#xD;
             cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal, endocrine,&#xD;
             psychiatric, or mental disease or disorder, or mental or legal incapacitation, which,&#xD;
             in the opinion of the PI or Sub-Investigator(s), may either put the subject at risk&#xD;
             because of participation in the study, influence the results of the study, or&#xD;
             influence the subject's ability to participate in the study&#xD;
&#xD;
          2. Clinical laboratory values that fall outside the eligibility range specified in&#xD;
             Appendix D; for laboratory values that are not included in Appendix D, values outside&#xD;
             the reference range are exclusionary, with the following exceptions (Table 4.&#xD;
             Acceptable Out-of-Range Clinical Laboratory Values&#xD;
&#xD;
          3. Known allergy to tetracycline antibiotics or to any of the excipients in TP-271&#xD;
&#xD;
          4. Clinically significant abnormality on a 12-lead ECG, including the following:&#xD;
&#xD;
               -  Rhythm other than sinus&#xD;
&#xD;
               -  Corrected QT interval using Fridericia's formula (QTcF) &gt;450 msec&#xD;
&#xD;
               -  Evidence of second- or third-degree atrioventricular block&#xD;
&#xD;
               -  Pathological Q-waves (defined as Q-wave &gt;40 msec or depth &gt;0.4 to 0.5 mV)&#xD;
&#xD;
               -  Evidence of ventricular pre-excitation&#xD;
&#xD;
               -  Evidence of complete left bundle branch block (BBB), right BBB, or incomplete&#xD;
                  left BBB&#xD;
&#xD;
               -  Intraventricular conduction delay with QRS duration &gt;120 msec&#xD;
&#xD;
               -  ST segment abnormalities, unless judged by the PI or Sub-Investigator(s) to be&#xD;
                  non pathologic&#xD;
&#xD;
          5. History of seizures&#xD;
&#xD;
          6. History within 3 years of a positive result on a urine screen for drugs of abuse or a&#xD;
             positive result at Screening for any of the following drugs of abuse:&#xD;
             tetrahydrocannabinols, cocaine, opioids, phencyclidines, amphetamine, benzodiazepine,&#xD;
             and barbiturates&#xD;
&#xD;
          7. Use of tobacco, nicotine, or nicotine-replacement products within 3 months prior to&#xD;
             administration of the study drug through the last visit&#xD;
&#xD;
          8. Typical weekly alcohol consumption of 7 or more alcoholic drinks, where 1 alcoholic&#xD;
             drink is defined as 1 glass of beer (approximately 10 to 12 oz), 1 can (12 oz) of&#xD;
             beer, 1 glass of wine (approximately 4 to 5 oz), or distilled spirits (approximately 1&#xD;
             oz or 30 mL of liquor)&#xD;
&#xD;
          9. Alcohol consumption within 48 hours prior to dosing&#xD;
&#xD;
         10. Participation in a clinical study within 10 half-lives of the prior study drug&#xD;
             administration or within the previous 3 months if the half-life or dose of the&#xD;
             investigational agent is unknown or planned participation in another clinical study&#xD;
             concurrent with the current clinical study&#xD;
&#xD;
         11. History of difficulty donating blood or poor venous access&#xD;
&#xD;
         12. Blood donation (1 unit or approximately 350 mL) within 1 month prior to receiving&#xD;
             study drug or plans to donate prior to receiving study drug or during the clinical&#xD;
             study&#xD;
&#xD;
         13. Use of any prescription or nonprescription medication, including vitamins or herbal&#xD;
             medications, vaccination, or immunization within 7 days or 5 half-lives (if known),&#xD;
             whichever is longer, prior to dosing of study drug, with the following exceptions:&#xD;
             medications used to treat an AE, and the use of acetaminophen, naproxen, and ibuprofen&#xD;
             (except for within 24 hours prior to dosing)&#xD;
&#xD;
         14. Male subject donates or plans to donate sperm during the study and for at least 90&#xD;
             days after study drug administration.&#xD;
&#xD;
         15. Unwillingness or inability to follow the procedures outlined in the clinical study&#xD;
             protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>PPD Phase 1 Clinic</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 6, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>December 9, 2021</last_update_submitted>
  <last_update_submitted_qc>December 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2021</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>Bacterial Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03234738
org study id: TP-271-002
secondary id: HHSN272201100028C
nct id: NCT03234738
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single-center, randomized, placebo-controlled, double-blind,
      multiple-ascending-dose, inpatient study to assess the safety, tolerability, and
      pharmacokinetics of TP-271 in healthy subjects. Subjects aged 18 to 50 years who fulfill the
      inclusion/exclusion criteria will be enrolled in this study.
Up to 5 cohorts of 8 subjects each (up to a total of 40 subjects) will be enrolled. The 8
      subjects within each cohort will be randomized 6:2 to receive multiple IV doses of TP-271 or
      placebo. Study drug will be administered IV once daily on the morning of Days 1 through 7
      following an overnight fast (minimum 8 hours). The planned doses for study drug for Cohorts A
      - E are 0.5 mg/kg TP-271 or placebo, 1.0 mg/kg TP-271 or placebo, 2.0 mg/kg TP-271 or
      placebo, 2.5 mg/kg TP-271 or placebo and 3.0 mg/kg TP-271 or placebo respectively.

      During the Screening period (Days -28 to -2 prior to the subject receiving TP-271 or
      placebo), each subject will be assessed for eligibility. Each subject must sign and date the
      ICF prior to undergoing any study-related procedures.

      All cohorts will follow the same study design. On Day -1, subjects will be admitted to the
      study unit and eligibility confirmed. On Day 1, eligible subjects will be enrolled and
      randomized to receive either TP-271 or placebo and will receive the assigned drug from Days 1
      through 7. Subjects will be required to stay at the study unit from Days -1 through 11 to
      assess safety and obtain the required PK samples. On Day 11, subjects will be discharged from
      the study unit. A final safety assessment will be performed once between Days 14 and 20, 7 to
      13 days following administration of the subject's final dose of study drug.

      After all 8 subjects in a cohort have completed study procedures through Day 11, the
      Principal Investigator and the Sponsor's Medical Monitor will evaluate all blinded safety and
      plasma PK data to determine whether any criteria that would require a meeting of the Safety
      Monitoring Committee (SMC) are met. If no such criteria are met, the study may proceed to the
      subsequent cohort at the next higher dose of TP-271 without consulting the SMC.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Five Multiple-Ascending Doses
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: IV bags and lines are covered to prevent unblinding.
measure: Adverse Events
time frame: Throughout the study, ~ 49 days
description: Incidence, intensity, and type of adverse events (AEs) from the time of signing the informed consent form (ICF) through the EOS Visit
measure: Physical Exams
time frame: ~ 20 days
description: Changes in physical examination findings between Day -1 and the EOS Visit
measure: Vital Signs
time frame: ~ 20 days
description: Changes in vital signs from Day -1 through the EOS Visit
measure: Safety Laboratory Results
time frame: ~ 20 days
description: Changes in safety laboratory (clinical chemistry, electrolytes, hematology, blood glucose, and coagulation) results from Day -1 through the EOS Visit
measure: ECG measurements
time frame: ~ 20 days
description: Changes in electrocardiogram (ECG) measurements from Day -1 through the EOS Visit
measure: Assess the Pharmacokinetics (PK) of TP-271in Plasma
time frame: ~11 days
description: Plasma concentrations of TP-271 and its C-4 epimer, TP-9555, for PK analysis from Days 1 through 11
measure: Assess the Pharmacokinetics (PK) of TP-271 in Urine
time frame: ~11 days
description: Urine concentrations of TP-271 and its C-4 epimer, TP-9555, from Days 1 through 11
arm group label: Cohort A
arm group type: Active Comparator
description: Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 0.5 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion
arm group label: Cohort B
arm group type: Active Comparator
description: Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 1.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion
arm group label: Cohort C
arm group type: Active Comparator
description: Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion
arm group label: Cohort D
arm group type: Active Comparator
description: Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.5 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion
arm group label: Cohort E
arm group type: Active Comparator
description: Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 3.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion
intervention type: Drug
intervention name: TP-271
description: multiple oral doses of TP-271 or placebo, dosed once daily for 7 days, randomized 3:1, doses escalating as 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort D
arm group label: Cohort E
intervention type: Drug
intervention name: Placebo
description: Placebo is sterile 0.45% saline randomized 3:1 to receive
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort D
arm group label: Cohort E
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Bacterial Infections
sharing ipd: No