<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/NCT04476407</url>
  </required_header>
  <id_info>
    <org_study_id>5081-I-1004</org_study_id>
    <nct_id>NCT04476407</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Benapenem in Subjects With Renal Impairment</brief_title>
  <official_title>&quot;Pharmacokinetics of Benapenem in Subjects With Mild or Moderate Renal Impairment &quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sihuan Pharmaceutical Holdings Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sihuan Pharmaceutical Holdings Group Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, multiple center, parallel-group Study to compare the pharmacokinetics&#xD;
      and safety of single-dose benapenem (1.0mg) in subjects with mild or moderate Renal&#xD;
      Impairment(RI) and healthy subjects. Subjects were enrolled with defined degrees of RI based&#xD;
      on eGFR(estimated Glomerular Filtration Rate) calculated by MDRD (Modification of Diet in&#xD;
      Renal Disease)formular as follows: nomal renal function(≥90ml/min/1.73m2 ; N=6); mild RI&#xD;
      (60-89mL/min/1.73 m2 ; N=6), moderate RI (30-59 mL/min/1.73m2 ; N=6)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2019</start_date>
  <completion_date type="Actual">October 21, 2019</completion_date>
  <primary_completion_date type="Actual">October 21, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve</measure>
    <time_frame>predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose</time_frame>
    <description>Area under the plasma concentration-time curve from time 0 to the time of thelast quantifiable concentration (AUC0-t )of benapenem and the metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve</measure>
    <time_frame>predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose</time_frame>
    <description>Area under the plasma concentration-time curve from time 0 to infinity ( AUC0-inf ) of benapenem and the metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration(Cmax)</measure>
    <time_frame>predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose</time_frame>
    <description>Maximum observed plasma concentration(Cmax) of benapenem and the metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Observed terminal elimination half-life (T1/2)</measure>
    <time_frame>predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Observed terminal elimination half-life (T1/2) of benapenem and its metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total body clearance (CLt)</measure>
    <time_frame>predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Total body clearance (CLt) of benapenem</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution (Vz)</measure>
    <time_frame>predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Apparent volume of distribution (Vz) based on the terminal phase of benapenem</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative urine exeretion</measure>
    <time_frame>predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Cumulative urine exeretion (Ae0-72h%) of benapenem and its metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal clearance (CLr)</measure>
    <time_frame>predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Renal clearance (CLr) of Benapenem and its metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolite-to-parent ratio of AUC0-inf</measure>
    <time_frame>predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Metabolite-to-parent ratio of AUC0-inf (MR)</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Complicated Urinary Tract Infection; Cuti</condition>
  <arm_group>
    <arm_group_label>G1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects with nomal renal function</description>
  </arm_group>
  <arm_group>
    <arm_group_label>G2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects with mild renal impairment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>G3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects with moderate renal impairment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>benapenem</intervention_name>
    <description>single-dose Benapenem 1.0mg(iv), 60min infusion</description>
    <arm_group_label>G1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>benapenem</intervention_name>
    <description>single-dose Benapenem 1.0mg(iv), 60min infusion</description>
    <arm_group_label>G2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>benapenem</intervention_name>
    <description>single-dose Benapenem 1.0mg(iv), 60min infusion</description>
    <arm_group_label>G3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1.18~75 years old&#xD;
&#xD;
          -  2. BMI 17 to 30 kg/m2&#xD;
&#xD;
          -  3. No known diseases or significant abnormalities on physical exam (subjects with&#xD;
             normal renal function only)&#xD;
&#xD;
          -  4. eGFR ≥ 90 mL/min/1.73m2 (subjects with normal renal function only)&#xD;
&#xD;
          -  5. eGFR 30 to 59 mL/min/1.73m2 (subjects with mild renal impairment only); eGFR 60 to&#xD;
             89 mL/min/1.73m2 (subjects with moderate renal impairment only)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Hypersensitivity to any of the beta-lactam antibiotics&#xD;
&#xD;
          -  2.Conditions or disease that may interfere with the evaluation of study drug&#xD;
&#xD;
          -  3. Acute disease requiring antibiotics within 30 days prior to administration, or a&#xD;
             fever within 7 days prior to administration;&#xD;
&#xD;
          -  4. Drug abuse in 2 years&#xD;
&#xD;
          -  5. A blood donation or more than 400 ml of blood loss within 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai Tongji Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 15, 2020</last_update_submitted>
  <last_update_submitted_qc>July 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2020</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>Urinary Tract Infections</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04476407
org study id: 5081-I-1004
nct id: NCT04476407
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is an open-label, multiple center, parallel-group Study to compare the pharmacokinetics
      and safety of single-dose benapenem (1.0mg) in subjects with mild or moderate Renal
      Impairment(RI) and healthy subjects. Subjects were enrolled with defined degrees of RI based
      on eGFR(estimated Glomerular Filtration Rate) calculated by MDRD (Modification of Diet in
      Renal Disease)formular as follows: nomal renal function(≥90ml/min/1.73m2 ; N=6); mild RI
      (60-89mL/min/1.73 m2 ; N=6), moderate RI (30-59 mL/min/1.73m2 ; N=6)
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the plasma concentration-time curve
time frame: predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose
description: Area under the plasma concentration-time curve from time 0 to the time of thelast quantifiable concentration (AUC0-t )of benapenem and the metabolite
measure: Area under the plasma concentration-time curve
time frame: predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose
description: Area under the plasma concentration-time curve from time 0 to infinity ( AUC0-inf ) of benapenem and the metabolite
measure: Maximum observed plasma concentration(Cmax)
time frame: predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose
description: Maximum observed plasma concentration(Cmax) of benapenem and the metabolite
measure: Observed terminal elimination half-life (T1/2)
time frame: predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose
description: Observed terminal elimination half-life (T1/2) of benapenem and its metabolite
measure: Total body clearance (CLt)
time frame: predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose
description: Total body clearance (CLt) of benapenem
measure: Apparent volume of distribution (Vz)
time frame: predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose
description: Apparent volume of distribution (Vz) based on the terminal phase of benapenem
measure: Cumulative urine exeretion
time frame: predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose
description: Cumulative urine exeretion (Ae0-72h%) of benapenem and its metabolite
measure: Renal clearance (CLr)
time frame: predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose
description: Renal clearance (CLr) of Benapenem and its metabolite
measure: Metabolite-to-parent ratio of AUC0-inf
time frame: predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose
description: Metabolite-to-parent ratio of AUC0-inf (MR)
arm group label: G1
arm group type: Experimental
description: subjects with nomal renal function
arm group label: G2
arm group type: Experimental
description: subjects with mild renal impairment
arm group label: G3
arm group type: Experimental
description: subjects with moderate renal impairment
intervention type: Drug
intervention name: benapenem
description: single-dose Benapenem 1.0mg(iv), 60min infusion
arm group label: G1
intervention type: Drug
intervention name: benapenem
description: single-dose Benapenem 1.0mg(iv), 60min infusion
arm group label: G2
intervention type: Drug
intervention name: benapenem
description: single-dose Benapenem 1.0mg(iv), 60min infusion
arm group label: G3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Urinary Tract Infections