<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/NCT04434300</url>
  </required_header>
  <id_info>
    <org_study_id>2019-004884-32</org_study_id>
    <nct_id>NCT04434300</nct_id>
  </id_info>
  <brief_title>Subcutaneous Daptomycin in Healthy Volunteers (DAPTOSC)</brief_title>
  <acronym>DAPTOSC</acronym>
  <official_title>Comparison of the Pharmacokinetic and the Safety of Daptomycin Administered Subcutaneously Compared to the Intravenous Route : a Cross-over Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Caen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Caen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Multidrug-resistant bacteria are a major public health problem worldwide, notably due to&#xD;
      excess mortality and an increase in the length of hospital stay. Antibiotics that can be used&#xD;
      to treat these infections are limited. Daptomycin is one of the most widely used antibiotics&#xD;
      for the treatment of infections with gram-positive bacteria, such as methicillin-resistant&#xD;
      Staphylococcus aureus (MRSA). However, it is only administered intravenously (IV). It is&#xD;
      therefore interesting to find new routes of administration in order to widen the&#xD;
      possibilities of using daptomycin, especially in people who have difficulties with the venous&#xD;
      approach.&#xD;
&#xD;
      Methods/design:&#xD;
&#xD;
      In a randomized, single blinded, crossover, noninferiority study in the CHU of Caen, the&#xD;
      investigators aim to demonstrate the pharmacokinetic bioequivalence between the subcutaneous&#xD;
      and the intravenous route of daptomycin in healthy volunteers. They will conclude the&#xD;
      bioequivalence if the confidence interval of the area under the curve obtained is entirely&#xD;
      within the interval [80% - 125%].&#xD;
&#xD;
      Discussion:&#xD;
&#xD;
      This clinical trial could, if bioequivalence is demonstrated, lead to the completion of a&#xD;
      clinical trial in infected patients in order to assess the efficacy and safety of daptomycin&#xD;
      by the subcutaneous route.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Actual">November 15, 2021</completion_date>
  <primary_completion_date type="Actual">January 15, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Subcutaneous administration of daptomycin and placebo will be done blind to the participant. Given the yellow coloration of daptomycin, a masking of the pockets of daptomycin and NaCl will be carried out with a pocket cover and an opaque tube will be used for the administration</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>before injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>30 minutes after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>1 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>1,50 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>2 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>3 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>4 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>8 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>10 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after intravenous route</measure>
    <time_frame>24 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after intravenous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>before injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>30 minutes after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>1 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>1.50 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>2 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>3 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>4 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>8 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>10 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <primary_outcome>
    <measure>daptomycin dosage after subcutaneous route</measure>
    <time_frame>24 hours after injection</time_frame>
    <description>measurement of daptomycin blood concentration after subcutaneous route</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local adverse events</measure>
    <time_frame>within the first 24hours after injection</time_frame>
    <description>Occurrence of local adverse events (pain, erythema, edema, necrosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local adverse events</measure>
    <time_frame>3 days after the infusion</time_frame>
    <description>Occurrence of local adverse events (pain, erythema, edema, necrosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local adverse events</measure>
    <time_frame>7 days after the infusion</time_frame>
    <description>Occurrence of local adverse events (pain, erythema, edema, necrosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic adverse events</measure>
    <time_frame>within the first 24hours after injection</time_frame>
    <description>Occurrence of systemic adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic adverse events</measure>
    <time_frame>3 days after the infusion</time_frame>
    <description>Occurrence of systemic adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic adverse events</measure>
    <time_frame>7 days after the infusion</time_frame>
    <description>Occurrence of systemic adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Antibiotics</condition>
  <condition>Subcutaneous Injection</condition>
  <condition>Daptomycin</condition>
  <arm_group>
    <arm_group_label>Dapto SC-IV</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>First stage :&#xD;
Subcutaneous injection of daptomycin 10mg/kg&#xD;
Subcutaneous injection of placebo (physiological serum)&#xD;
Second stage :&#xD;
- Intravenous injection of daptomycin 10mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dapto IV-SC</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>First stage :&#xD;
- Intravenous injection of daptomycin 10mg/kg&#xD;
Second stage :&#xD;
Subcutaneous injection of daptomycin 10mg/kg&#xD;
Subcutaneous injection of placebo (physiological serum)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daptomycin</intervention_name>
    <description>Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.</description>
    <arm_group_label>Dapto SC-IV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daptomycin</intervention_name>
    <description>Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.</description>
    <arm_group_label>Dapto IV-SC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteer from 18 to 65 years old&#xD;
&#xD;
          -  Subject determined in good health by a doctor&#xD;
&#xD;
          -  Signature of free and informed consent&#xD;
&#xD;
          -  Affiliated to the French healthcare insurance&#xD;
&#xD;
          -  Fluent in French&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active bacterial or viral infection&#xD;
&#xD;
          -  Immunocompromised&#xD;
&#xD;
          -  Body mass index &lt;20 or&gt; 30 kg / m2&#xD;
&#xD;
          -  Kidney failure with glomerular filtration rate &lt;90ml / min / m2 calculated according&#xD;
             to the CKD-EPI method&#xD;
&#xD;
          -  Known or suspected liver disease&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Guardianship or curators&#xD;
&#xD;
          -  Any situation that could interfere with the self / hetero assessment of pain&#xD;
             (dementia, psychiatric disorders, for example)&#xD;
&#xD;
          -  Concomitant intake of myotoxic drugs (statins, fibrates, ciclosporin, for example)&#xD;
&#xD;
          -  Allergy or known side effects to daptomycin&#xD;
&#xD;
          -  Dermatological pathologies which may interfere with the subcutaneous injection&#xD;
             (eczema, psoriasis, etc.)&#xD;
&#xD;
          -  Localized tattoo or piercing on the abdomen which may interfere with the subcutaneous&#xD;
             injection or the evaluation of possible local effects of the injection&#xD;
&#xD;
          -  Parenteral exposure to daptomycin in the previous 30 days&#xD;
&#xD;
          -  The inclusion of the subject in another interventional research protocol (during the&#xD;
             present study and in the 3 months before inclusion).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CHU Caen</name>
      <address>
        <city>Caen</city>
        <state>Normandie</state>
        <zip>14000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>April 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>January 31, 2022</last_update_submitted>
  <last_update_submitted_qc>January 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Daptomycin</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/NCT04434300
org study id: 2019-004884-32
nct id: NCT04434300
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Background:

      Multidrug-resistant bacteria are a major public health problem worldwide, notably due to
      excess mortality and an increase in the length of hospital stay. Antibiotics that can be used
      to treat these infections are limited. Daptomycin is one of the most widely used antibiotics
      for the treatment of infections with gram-positive bacteria, such as methicillin-resistant
      Staphylococcus aureus (MRSA). However, it is only administered intravenously (IV). It is
      therefore interesting to find new routes of administration in order to widen the
      possibilities of using daptomycin, especially in people who have difficulties with the venous
      approach.

      Methods/design:

      In a randomized, single blinded, crossover, noninferiority study in the CHU of Caen, the
      investigators aim to demonstrate the pharmacokinetic bioequivalence between the subcutaneous
      and the intravenous route of daptomycin in healthy volunteers. They will conclude the
      bioequivalence if the confidence interval of the area under the curve obtained is entirely
      within the interval [80% - 125%].

      Discussion:

      This clinical trial could, if bioequivalence is demonstrated, lead to the completion of a
      clinical trial in infected patients in order to assess the efficacy and safety of daptomycin
      by the subcutaneous route.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Participant)
masking description: Subcutaneous administration of daptomycin and placebo will be done blind to the participant. Given the yellow coloration of daptomycin, a masking of the pockets of daptomycin and NaCl will be carried out with a pocket cover and an opaque tube will be used for the administration
measure: daptomycin dosage after intravenous route
time frame: before injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 30 minutes after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 1 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 1,50 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 2 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 3 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 4 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 8 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 10 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after intravenous route
time frame: 24 hours after injection
description: measurement of daptomycin blood concentration after intravenous route
measure: daptomycin dosage after subcutaneous route
time frame: before injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 30 minutes after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 1 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 1.50 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 2 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 3 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 4 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 8 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 10 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: daptomycin dosage after subcutaneous route
time frame: 24 hours after injection
description: measurement of daptomycin blood concentration after subcutaneous route
measure: Local adverse events
time frame: within the first 24hours after injection
description: Occurrence of local adverse events (pain, erythema, edema, necrosis)
measure: Local adverse events
time frame: 3 days after the infusion
description: Occurrence of local adverse events (pain, erythema, edema, necrosis)
measure: Local adverse events
time frame: 7 days after the infusion
description: Occurrence of local adverse events (pain, erythema, edema, necrosis)
measure: Systemic adverse events
time frame: within the first 24hours after injection
description: Occurrence of systemic adverse events
measure: Systemic adverse events
time frame: 3 days after the infusion
description: Occurrence of systemic adverse events
measure: Systemic adverse events
time frame: 7 days after the infusion
description: Occurrence of systemic adverse events
arm group label: Dapto SC-IV
arm group type: Other
description: First stage :
Subcutaneous injection of daptomycin 10mg/kg
Subcutaneous injection of placebo (physiological serum)
Second stage :
- Intravenous injection of daptomycin 10mg/kg
arm group label: Dapto IV-SC
arm group type: Other
description: First stage :
- Intravenous injection of daptomycin 10mg/kg
Second stage :
Subcutaneous injection of daptomycin 10mg/kg
Subcutaneous injection of placebo (physiological serum)
intervention type: Drug
intervention name: Daptomycin
description: Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.
arm group label: Dapto SC-IV
intervention type: Drug
intervention name: Daptomycin
description: Compare the pharmacokinetic of subcutaneous (SC) and intravenous (IV) routes in the same patient.
arm group label: Dapto IV-SC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: France
responsible party type: Sponsor
mesh term: Daptomycin