<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/NCT04421885</url>
  </required_header>
  <id_info>
    <org_study_id>SPR994-105</org_study_id>
    <nct_id>NCT04421885</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study Comparing Two Tablet Formulations of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects</brief_title>
  <official_title>An Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover, Bioequivalence Study Comparing Two Tablet Formulations of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spero Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spero Therapeutics</source>
  <oversight_info>
    <has_dmc>No</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>
      A bioequivalence and food-effect study comparing two tablet formulations of tebipenem pivoxil&#xD;
      hydrobromide (TBPM-PI-HBr) in healthy adult subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">July 29, 2020</completion_date>
  <primary_completion_date type="Actual">July 11, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the curve extrapolated to infinity (AUC0-∞).</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t).</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax).</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to the maximum plasma concentration (Tmax).</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life (t½).</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CL/F)</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).</measure>
    <time_frame>24h (Day 2) post dose (Arms: A, B, C)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.</measure>
    <time_frame>12 to 14 days after the last dose of study drug</time_frame>
    <description>ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve extrapolated to infinity (AUC0-∞).</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t).</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax).</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to the maximum plasma concentration (Tmax).</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life (t½).</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CL/F)</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).</measure>
    <time_frame>24h (Day 2) post dose (Arms: B, C)</time_frame>
    <description>TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>A: TBPM-PI-HBr (Reference - fasted)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: TBPM-PI-HBr (Test - fasted)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: TBPM-PI-HBr (Test - fed)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fed conditions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference</intervention_name>
    <description>600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr.</description>
    <arm_group_label>A: TBPM-PI-HBr (Reference - fasted)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test</intervention_name>
    <description>600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.</description>
    <arm_group_label>B: TBPM-PI-HBr (Test - fasted)</arm_group_label>
    <arm_group_label>C: TBPM-PI-HBr (Test - fed)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy, adult, male or female, 18 to 55 years of age&#xD;
&#xD;
          -  Continuous non-smoker.&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2.&#xD;
&#xD;
          -  Medically healthy with no clinically significant medical history, physical&#xD;
             examination, laboratory profiles, vital signs or ECGs.&#xD;
&#xD;
          -  Has suitable venous access for repeated blood sampling.&#xD;
&#xD;
          -  A female of childbearing potential must agree to abstain from sexual activity that&#xD;
             could lead to pregnancy.&#xD;
&#xD;
          -  A female of non-childbearing potential.&#xD;
&#xD;
          -  Understands the study procedures in the informed consent form (ICF), and be willing&#xD;
             and able to comply with the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is mentally or legally incapacitated or has significant emotional problems at the time&#xD;
             of the screening visit or expected to have during the conduct of the study.&#xD;
&#xD;
          -  History or presence of clinically significant medical or psychiatric condition or&#xD;
             disease.&#xD;
&#xD;
          -  History of any illness that might confound the results of the study or poses an&#xD;
             additional risk to the subject by their participation in the study.&#xD;
&#xD;
          -  History of significant allergic disease requiring treatment.&#xD;
&#xD;
          -  History or presence of alcoholism or drug abuse.&#xD;
&#xD;
          -  History or presence of hypersensitivity or idiosyncratic reaction to the study drug or&#xD;
             related compounds.&#xD;
&#xD;
          -  History of known genetic metabolism anomaly associated with carnitine deficiency.&#xD;
&#xD;
          -  Female subjects with a positive pregnancy test or who are lactating.&#xD;
&#xD;
          -  Positive urine drug or alcohol results.&#xD;
&#xD;
          -  Positive results for human immunodeficiency virus (HIV 1 and 2), hepatitis B surface&#xD;
             antigen (HBsAg), or hepatitis C virus (HCV).&#xD;
&#xD;
          -  QTcF interval is &gt; 460 msec (males) or &gt; 470 msec (females) or has ECG findings deemed&#xD;
             abnormal with clinical significance by the PI or designee at the screening visit.&#xD;
&#xD;
          -  Estimated creatinine clearance &lt; 80 mL/min at the screening visit.&#xD;
&#xD;
          -  Unable to refrain from or anticipates the use of any drug, including prescription and&#xD;
             non-prescription medications, herbal remedies, or vitamin supplements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Melnick</last_name>
    <role>Study Director</role>
    <affiliation>Spero Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical Facility</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>August 10, 2020</last_update_submitted>
  <last_update_submitted_qc>August 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04421885
org study id: SPR994-105
nct id: NCT04421885
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A bioequivalence and food-effect study comparing two tablet formulations of tebipenem pivoxil
      hydrobromide (TBPM-PI-HBr) in healthy adult subjects.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover
primary purpose: Other
masking: None (Open Label)
measure: Area under the curve extrapolated to infinity (AUC0-∞).
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t).
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Maximum plasma concentration (Cmax).
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Time to the maximum plasma concentration (Tmax).
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Terminal elimination half-life (t½).
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Apparent total body clearance (CL/F)
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).
time frame: 24h (Day 2) post dose (Arms: A, B, C)
measure: Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.
time frame: 12 to 14 days after the last dose of study drug
description: ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.
measure: Area under the curve extrapolated to infinity (AUC0-∞).
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
measure: Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t).
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
measure: Maximum plasma concentration (Cmax).
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
measure: Time to the maximum plasma concentration (Tmax).
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
measure: Terminal elimination half-life (t½).
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
measure: Apparent total body clearance (CL/F)
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
measure: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).
time frame: 24h (Day 2) post dose (Arms: B, C)
description: TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.
arm group label: A: TBPM-PI-HBr (Reference - fasted)
arm group type: Experimental
description: 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.
arm group label: B: TBPM-PI-HBr (Test - fasted)
arm group type: Experimental
description: 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.
arm group label: C: TBPM-PI-HBr (Test - fed)
arm group type: Experimental
description: 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fed conditions.
intervention type: Drug
intervention name: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference
description: 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr.
arm group label: A: TBPM-PI-HBr (Reference - fasted)
intervention type: Drug
intervention name: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test
description: 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.
arm group label: B: TBPM-PI-HBr (Test - fasted)
arm group label: C: TBPM-PI-HBr (Test - fed)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Melnick
role: Study Director
affiliation: Spero Therapeutics
facility: 
country: United States
responsible party type: Sponsor