<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/NCT01702649</url>
  </required_header>
  <id_info>
    <org_study_id>Rempex 401</org_study_id>
    <nct_id>NCT01702649</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 (Biapenem) in Healthy Adult Subjects</brief_title>
  <official_title>A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single- and Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      RPX2003 (biapenem) is being studied in combination with a beta-lactamase inhibitor to treat&#xD;
      bacterial infections, including those due to multi-drug resistant bacteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The worldwide spread of resistance to antibiotics among Gram-negative bacteria, particularly&#xD;
      members of the ESKAPE group of pathogens, has resulted in a crisis in the treatment of&#xD;
      hospital acquired infections. In particular, the recent dissemination of a serine&#xD;
      carbapenemase (e.g., KPC) in Enterobacteriaceae in US hospitals now poses a considerable&#xD;
      threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.&#xD;
&#xD;
      Rempex is developing a fixed combination antibiotic of a carbapenem (RPX2003 or biapenem)&#xD;
      plus a new beta-lactamase inhibitor (RPX7009) which has activity against serine&#xD;
      beta-lactamases, including KPC. This Phase 1 study will assess the safety, tolerability and&#xD;
      pharmacokinetics of biapenem, administered alone, in healthy adult subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety from baseline through the end of the study.</measure>
    <time_frame>Study Day 1 to 13.</time_frame>
    <description>Number of patients with adverse events; assessed by patient reporting, collection of vital signs, ECGs and absolute values and changes over time of hematology, chemistry and urinalysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters RPX2003 &amp; placebo following single dose administration.</measure>
    <time_frame>Part 1A Study Day 1 to 3.</time_frame>
    <description>plasma AUC0-t, AUC0-inf, Cmax, and Tmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters RPX2003 &amp; placebo following multiple dose administration.</measure>
    <time_frame>Part 1B Day 4 to 12</time_frame>
    <description>plasma AUC0-t, AUC0-inf, Cmax, and Tmax.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Healthy Volunteers</condition>
  <condition>Bacterial Infections</condition>
  <arm_group>
    <arm_group_label>RPX2003 (Biapenem)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single and multiple dose of RPX2003 (Biapenem).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single and multiple doses of normal saline.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RPX2003 (Biapenem)</intervention_name>
    <description>Six (6) cohorts of 3 active or 8 subjects of 6 active are planned for evaluation.&#xD;
Single dose followed by multiple dose, three times a day.</description>
    <arm_group_label>RPX2003 (Biapenem)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Six (6) cohorts of 1 placebo or 8 subjects of 2 placebo are planned for evaluation.&#xD;
Single dose followed by multiple dose, three times a day.</description>
    <arm_group_label>Normal Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adult males and/or females, 18 to 55 years of age&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg&#xD;
             (inclusive).&#xD;
&#xD;
          -  Medically healthy with clinically insignificant screening results&#xD;
&#xD;
          -  Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Day&#xD;
             1.&#xD;
&#xD;
          -  Sexually abstinent or use acceptable methods of birth control&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of significant cardiovascular, pulmonary, hepatic, renal,&#xD;
             hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological,&#xD;
             or psychiatric disease.&#xD;
&#xD;
          -  History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.&#xD;
&#xD;
          -  Hypersensitivity or idiosyncratic reaction to compounds related to the study drug&#xD;
             (e.g. beta-lactam antibiotics such as penicillins, carbapenems, etc).&#xD;
&#xD;
          -  History of seizures (e.g., epilepsy).&#xD;
&#xD;
          -  Use of any over-the-counter (OTC) medication, including herbal products and vitamins,&#xD;
             within the 7 days prior to Day 1. Up to 2 grams per day of acetaminophen is allowed&#xD;
             for acute events at the discretion of the PI.&#xD;
&#xD;
          -  Blood donation or significant blood loss (i.e., &gt; 500 mL) within 56 days prior to Day&#xD;
             1.&#xD;
&#xD;
          -  Subjects who have any abnormalities on laboratory values at screening or check-in (Day&#xD;
             -1).&#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>Jeff Loutit, MBChB</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion</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>November 2012</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <last_update_submitted>November 29, 2012</last_update_submitted>
  <last_update_submitted_qc>November 29, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2012</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Biapenem</mesh_term>
  </intervention_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/NCT01702649
org study id: Rempex 401
nct id: NCT01702649
lead sponsor: 
has dmc: No
RPX2003 (biapenem) is being studied in combination with a beta-lactamase inhibitor to treat
      bacterial infections, including those due to multi-drug resistant bacteria.
The worldwide spread of resistance to antibiotics among Gram-negative bacteria, particularly
      members of the ESKAPE group of pathogens, has resulted in a crisis in the treatment of
      hospital acquired infections. In particular, the recent dissemination of a serine
      carbapenemase (e.g., KPC) in Enterobacteriaceae in US hospitals now poses a considerable
      threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.

      Rempex is developing a fixed combination antibiotic of a carbapenem (RPX2003 or biapenem)
      plus a new beta-lactamase inhibitor (RPX7009) which has activity against serine
      beta-lactamases, including KPC. This Phase 1 study will assess the safety, tolerability and
      pharmacokinetics of biapenem, administered alone, in healthy adult subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Safety from baseline through the end of the study.
time frame: Study Day 1 to 13.
description: Number of patients with adverse events; assessed by patient reporting, collection of vital signs, ECGs and absolute values and changes over time of hematology, chemistry and urinalysis.
measure: Composite of PK parameters RPX2003 & placebo following single dose administration.
time frame: Part 1A Study Day 1 to 3.
description: plasma AUC0-t, AUC0-inf, Cmax, and Tmax.
measure: Composite of PK parameters RPX2003 & placebo following multiple dose administration.
time frame: Part 1B Day 4 to 12
description: plasma AUC0-t, AUC0-inf, Cmax, and Tmax.
arm group label: RPX2003 (Biapenem)
arm group type: Experimental
description: Single and multiple dose of RPX2003 (Biapenem).
arm group label: Normal Saline
arm group type: Placebo Comparator
description: Single and multiple doses of normal saline.
intervention type: Drug
intervention name: RPX2003 (Biapenem)
description: Six (6) cohorts of 3 active or 8 subjects of 6 active are planned for evaluation.
Single dose followed by multiple dose, three times a day.
arm group label: RPX2003 (Biapenem)
intervention type: Drug
intervention name: Placebo
description: Six (6) cohorts of 1 placebo or 8 subjects of 2 placebo are planned for evaluation.
Single dose followed by multiple dose, three times a day.
arm group label: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeff Loutit, MBChB
role: Study Director
affiliation: Sponsor GmbH
facility: 
country: United States
responsible party type: Sponsor
mesh term: Bacterial Infections
mesh term: Biapenem