<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/NCT04501107</url>
  </required_header>
  <id_info>
    <org_study_id>CT037-ADO02</org_study_id>
    <nct_id>NCT04501107</nct_id>
  </id_info>
  <brief_title>A Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus</brief_title>
  <official_title>A Randomised, Double Blind, Crossover Euglycaemic Clamp Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adocia</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adocia</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>
      This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic&#xD;
      clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly&#xD;
      allocated to one of four treatment sequences. Each sequence comprises one single dose of each&#xD;
      of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same&#xD;
      composition and correspond to different development stages of a unique product which is&#xD;
      BioChaperone insulin lispro; between them, improvements were made to prepare industrial&#xD;
      production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®.&#xD;
      All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a&#xD;
      washout period of 5 to 15 days.&#xD;
&#xD;
      The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2)&#xD;
      formulation to US-approved Humalog and EU-approved Humalog.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Actual">November 3, 2020</completion_date>
  <primary_completion_date type="Actual">November 3, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUCGIR.0-12h</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Area under the glucose infusion rate-time curve from time 0 until end of clamp</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCGIR.0-1h</measure>
    <time_frame>From t=0 to t=1 hour after IMP administration</time_frame>
    <description>Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCLIS.0-12h</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCLIS.0-1h</measure>
    <time_frame>From t=0 to t=1 hour after IMP administration</time_frame>
    <description>Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>tmax.LIS</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Time to maximum observed insulin lispro concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax.LIS</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Maximum observed insulin lispro concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCLIS.2-6h</measure>
    <time_frame>From t=2 to t=6hours after IMP administration</time_frame>
    <description>Area under the insulin lispro concentration-time curve from 2 hour to 6 hour after dose administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t50%-LIS (early)</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Time to half-maximum before Cmax.LIS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax.GIR</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Time to maximum glucose infusion rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GIRmax</measure>
    <time_frame>From t=0 to t=12 hours after IMP administration</time_frame>
    <description>Maximum glucose infusion rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCGIR.4-8h</measure>
    <time_frame>From t=4 to t=8 hours after IMP administration</time_frame>
    <description>Area under the glucose infusion rate-time curve from 4 to 8 hours after dose administration</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>BioChaperone insulin lispro reconstituted with Humalog® (IMP1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ready-to-use BioChaperone insulin lispro (IMP2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>US-approved Humalog® (IMP3)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EU-approved Humalog® (IMP4)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)</intervention_name>
    <description>Administration of IMP1 during a 12-hour euglycaemic clamp.</description>
    <arm_group_label>BioChaperone insulin lispro reconstituted with Humalog® (IMP1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of Ready-to-use BioChaperone insulin lispro (IMP2)</intervention_name>
    <description>Administration of IMP2 during a 12-hour euglycaemic clamp.</description>
    <arm_group_label>Ready-to-use BioChaperone insulin lispro (IMP2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of US-approved Humalog® (IMP3)</intervention_name>
    <description>Administration of IMP3 during a 12-hour euglycaemic clamp.</description>
    <arm_group_label>US-approved Humalog® (IMP3)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of EU-approved Humalog® (IMP4)</intervention_name>
    <description>Administration of IMP4 during a 12-hour euglycaemic clamp.</description>
    <arm_group_label>EU-approved Humalog® (IMP4)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with type 1 Diabetes Mellitus&#xD;
&#xD;
          -  Body Mass Index (BMI) between 18.5 and 28.5 kg/m^2, both inclusive&#xD;
&#xD;
          -  HbA1c &lt;= 75 mmol/mol (&lt;=9.0%).&#xD;
&#xD;
          -  Fasting negative C-peptide (&lt;= 0.30 nmol/L).&#xD;
&#xD;
          -  Total insulin dose of &lt; 1.2 (I)U/kg/day.&#xD;
&#xD;
          -  Stable insulin regimen (with respect to safety of the subject and scientific integrity&#xD;
             of the study) using continuous subcutaneous insulin infusion (CSII) or multiple daily&#xD;
             insulin injections (MDI) for at least 2 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or suspected hypersensitivity to IMP(s) or related products.&#xD;
&#xD;
          -  Receipt of any medicinal product in clinical development within 30 days or at least 5&#xD;
             half-lives of the related substances and their metabolites (whichever is longer)&#xD;
             before randomisation in this trial.&#xD;
&#xD;
          -  History of multiple and/or severe allergies to drugs or foods or a history of severe&#xD;
             anaphylactic reaction.&#xD;
&#xD;
          -  Any history or presence of cancer except basal cell skin cancer or squamous cell skin&#xD;
             cancer as judged by the Investigator.&#xD;
&#xD;
          -  Any history or presence of clinically relevant comorbidity capable of constituting a&#xD;
             risk for the subject when participating in the trial or of interfering with the&#xD;
             interpretation of data.&#xD;
&#xD;
          -  Signs of acute illness as judged by the Investigator.&#xD;
&#xD;
          -  Any serious systemic infectious disease during four weeks prior to first dosing of the&#xD;
             trial drug, as judged by the Investigator.&#xD;
&#xD;
          -  Clinically significant abnormal screening laboratory tests, as judged by the&#xD;
             Investigator.&#xD;
&#xD;
          -  Proliferative retinopathy or maculopathy as judged by the Investigator based on a&#xD;
             recent (&lt;1.5 years) ophthalmologic examination.&#xD;
&#xD;
          -  Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists within 3 months&#xD;
             prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eugen Baumgaertner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Profil GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Profil GmbH</name>
      <address>
        <city>Mainz</city>
        <zip>D-55116</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>November 27, 2020</last_update_submitted>
  <last_update_submitted_qc>November 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 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>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Insulin Lispro</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/NCT04501107
org study id: CT037-ADO02
nct id: NCT04501107
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic
      clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly
      allocated to one of four treatment sequences. Each sequence comprises one single dose of each
      of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same
      composition and correspond to different development stages of a unique product which is
      BioChaperone insulin lispro; between them, improvements were made to prepare industrial
      production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®.
      All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a
      washout period of 5 to 15 days.

      The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2)
      formulation to US-approved Humalog and EU-approved Humalog.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: AUCGIR.0-12h
time frame: From t=0 to t=12 hours after IMP administration
description: Area under the glucose infusion rate-time curve from time 0 until end of clamp
measure: AUCGIR.0-1h
time frame: From t=0 to t=1 hour after IMP administration
description: Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration
measure: AUCLIS.0-12h
time frame: From t=0 to t=12 hours after IMP administration
description: Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration
measure: AUCLIS.0-1h
time frame: From t=0 to t=1 hour after IMP administration
description: Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration
measure: tmax.LIS
time frame: From t=0 to t=12 hours after IMP administration
description: Time to maximum observed insulin lispro concentration
measure: Cmax.LIS
time frame: From t=0 to t=12 hours after IMP administration
description: Maximum observed insulin lispro concentration
measure: AUCLIS.2-6h
time frame: From t=2 to t=6hours after IMP administration
description: Area under the insulin lispro concentration-time curve from 2 hour to 6 hour after dose administration
measure: t50%-LIS (early)
time frame: From t=0 to t=12 hours after IMP administration
description: Time to half-maximum before Cmax.LIS
measure: tmax.GIR
time frame: From t=0 to t=12 hours after IMP administration
description: Time to maximum glucose infusion rate
measure: GIRmax
time frame: From t=0 to t=12 hours after IMP administration
description: Maximum glucose infusion rate
measure: AUCGIR.4-8h
time frame: From t=4 to t=8 hours after IMP administration
description: Area under the glucose infusion rate-time curve from 4 to 8 hours after dose administration
arm group label: BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
arm group type: Experimental
description: Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW).
arm group label: Ready-to-use BioChaperone insulin lispro (IMP2)
arm group type: Experimental
description: Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW.
arm group label: US-approved Humalog® (IMP3)
arm group type: Active Comparator
description: Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW.
arm group label: EU-approved Humalog® (IMP4)
arm group type: Active Comparator
description: Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW.
intervention type: Drug
intervention name: Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
description: Administration of IMP1 during a 12-hour euglycaemic clamp.
arm group label: BioChaperone insulin lispro reconstituted with Humalog® (IMP1)
intervention type: Drug
intervention name: Administration of Ready-to-use BioChaperone insulin lispro (IMP2)
description: Administration of IMP2 during a 12-hour euglycaemic clamp.
arm group label: Ready-to-use BioChaperone insulin lispro (IMP2)
intervention type: Drug
intervention name: Administration of US-approved Humalog® (IMP3)
description: Administration of IMP3 during a 12-hour euglycaemic clamp.
arm group label: US-approved Humalog® (IMP3)
intervention type: Drug
intervention name: Administration of EU-approved Humalog® (IMP4)
description: Administration of IMP4 during a 12-hour euglycaemic clamp.
arm group label: EU-approved Humalog® (IMP4)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Eugen Baumgaertner, MD
role: Principal Investigator
affiliation: Profil GmbH
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Lispro