<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/NCT02201199</url>
  </required_header>
  <id_info>
    <org_study_id>PDY13928</org_study_id>
    <secondary_id>2014-001252-33</secondary_id>
    <secondary_id>U1111-1153-3712</secondary_id>
    <nct_id>NCT02201199</nct_id>
  </id_info>
  <brief_title>Single Dose Clamp Study To Compare Concentration/Time Profile And Metabolic Activity Profile Of 2 New Formulations Of Insulin Glargine With Lantus</brief_title>
  <official_title>A Single-Center, Randomized, Double-Blind, 3-Treatment, 3-Period, 6-Sequence Cross-Over Study To Compare The Pharmacokinetic And Pharmacodynamic Effects of Single Doses of Insulin Glargine Given As U200 And U500 To Lantus® In A Euglycemic Clamp Setting In Subjects With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To compare the pharmacokinetic (PK) characteristics of single doses of insulin glargine given&#xD;
      as U200 and U500 with those of a single dose (SD) of Lantus® U100 in a euglycemic clamp&#xD;
      setting in subjects with type 1 diabetes.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      To compare the metabolic activity characteristics of single doses of insulin glargine given&#xD;
      as U200 and U500 with those of a single dose of Lantus® U100 in a euglycemic clamp setting in&#xD;
      subjects with type 1 diabetes.&#xD;
&#xD;
      To assess the safety and tolerability of single doses of U200, U500 and Lantus® U100 in&#xD;
      subjects with type 1 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Total study duration for each subject is between 3.5 and 12 weeks.&#xD;
&#xD;
      Two overnight stays at the unit in each of 3 treatment periods.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the serum insulin glargine (INS) concentration curve over the first 12 hours after dosing</measure>
    <time_frame>12 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36)</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC up to the last measurable concentration</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach 50% of INS-AUC 0-36</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach INS-Cmax (INS-tmax)</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the body-weight-standardized Glucose Infusion Rate (GIR) over the first 12, 24 and 36 hours after dosing (GIR-AUC0-12, GIR-AUC0-24 and, GIR-AUC0-36)</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36)</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum smoothed body weight standardized glucose infusion rate (GIRmax) and time to GIRmax (GIR-Tmax)</measure>
    <time_frame>36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different pre-specific blood glucose levels)</measure>
    <time_frame>4 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability (Number of patients with adverse events, clinically significant changes in vital signs, laboratory parameters)</measure>
    <time_frame>4 days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>insulin glargine U100</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>insulin glargine U200</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>insulin glargine U500</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin glargine U200 HOE901</intervention_name>
    <description>Pharmaceutical form:solution for injection Route of administration: subcutaneous</description>
    <arm_group_label>insulin glargine U200</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin glargine U500 HOE901</intervention_name>
    <description>Pharmaceutical form:solution for injection Route of administration: subcutaneous</description>
    <arm_group_label>insulin glargine U500</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin glargine U100 HOE901</intervention_name>
    <description>Pharmaceutical form:solution for injection Route of administration: subcutaneous</description>
    <arm_group_label>insulin glargine U100</arm_group_label>
    <other_name>Lantus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Male or female subjects, between 18 and 65 years of age, inclusive, with type 1&#xD;
             diabetes mellitus for more than one year, as defined by the American Diabetes&#xD;
             Association.&#xD;
&#xD;
          -  Total insulin dose &lt;1.2 U/kg/day.&#xD;
&#xD;
          -  Minimum usual basal insulin dose ≥0.2 U/kg/day.&#xD;
&#xD;
          -  Body weight between 50.0 kg and 110.0 kg, Body Mass Index between 18.5 and 30.0 kg/m2&#xD;
             inclusive.&#xD;
&#xD;
          -  Fasting negative serum C-peptide (&lt;0.3 nmol/L).&#xD;
&#xD;
          -  Glycohemoglobin (HbA1c) ≤75 mmol/mol (≤9.0%).&#xD;
&#xD;
          -  Stable insulin regimen for at least 2 months prior to inclusion in study.&#xD;
&#xD;
          -  Certified as otherwise healthy for Type 1 diabetes mellitus patient.&#xD;
&#xD;
          -  Women of childbearing potential with negative pregnancy test and use of a highly&#xD;
             effective contraceptive method or women with confirmed postmenopausal status.&#xD;
&#xD;
          -  Having given written informed consent prior to undertaking any study-related&#xD;
             procedure.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  More than one episode of severe hypoglycemia with seizure, coma or requiring&#xD;
             assistance of another person during the past 6 months.&#xD;
&#xD;
          -  Frequent severe headaches and / or migraine, recurrent nausea and / or vomiting (more&#xD;
             than twice a month).&#xD;
&#xD;
          -  Presence or history of a drug allergy or clinically significant allergic disease&#xD;
             according to the Investigator's judgment.&#xD;
&#xD;
          -  Presence or history of drug or alcohol abuse (alcohol consumption &gt;40 grams / day).&#xD;
&#xD;
          -  Smoking more than 5 cigarettes or equivalent per day, unable to refrain from smoking.&#xD;
&#xD;
          -  Any medication (including St John's Wort) within 14 days before inclusion, or within 5&#xD;
             times the elimination half-life or pharmacodynamic half-life of that drug, whichever&#xD;
             the longest and regular use of any medication in the last month before study start&#xD;
             with the exception of insulin products, thyroid hormones, lipid-lowering and&#xD;
             antihypertensive drugs, and, if female, with the exception of hormonal contraception&#xD;
             or menopausal hormone replacement therapy; any vaccination within the last 28 days;&#xD;
             any biologics (antibody or its derivatives) given within 4 months before&#xD;
             randomization.&#xD;
&#xD;
          -  Known hypersensitivity to insulin glargine or excipients of the study drug.&#xD;
&#xD;
          -  Any history or presence of deep leg vein thrombosis or a frequent appearance of deep&#xD;
             leg vein thrombosis in first degree relatives (parents, siblings or children).&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 276001</name>
      <address>
        <city>Neuss</city>
        <zip>41460</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>December 23, 2014</last_update_submitted>
  <last_update_submitted_qc>December 23, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 24, 2014</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, 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 Glargine</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/NCT02201199
org study id: PDY13928
secondary id: 2014-001252-33
secondary id: U1111-1153-3712
nct id: NCT02201199
lead sponsor: 
has dmc: No
Primary Objective:

      To compare the pharmacokinetic (PK) characteristics of single doses of insulin glargine given
      as U200 and U500 with those of a single dose (SD) of Lantus® U100 in a euglycemic clamp
      setting in subjects with type 1 diabetes.

      Secondary Objectives:

      To compare the metabolic activity characteristics of single doses of insulin glargine given
      as U200 and U500 with those of a single dose of Lantus® U100 in a euglycemic clamp setting in
      subjects with type 1 diabetes.

      To assess the safety and tolerability of single doses of U200, U500 and Lantus® U100 in
      subjects with type 1 diabetes.
Total study duration for each subject is between 3.5 and 12 weeks.

      Two overnight stays at the unit in each of 3 treatment periods.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Area under the serum insulin glargine (INS) concentration curve over the first 12 hours after dosing
time frame: 12 hours
measure: INS-Area Under the Curve (AUC) over 24 and 36 hours after dosing (INS AUC 0-24 and INS AUC 0-36)
time frame: 36 hours
measure: AUC up to the last measurable concentration
time frame: 36 hours
measure: Time to reach 50% of INS-AUC 0-36
time frame: 36 hours
measure: Time to reach INS-Cmax (INS-tmax)
time frame: 36 hours
measure: Area under the body-weight-standardized Glucose Infusion Rate (GIR) over the first 12, 24 and 36 hours after dosing (GIR-AUC0-12, GIR-AUC0-24 and, GIR-AUC0-36)
time frame: 36 hours
measure: Time to reach 50% of GIR-AUC0-36 (T50%-GIR-AUC0-36)
time frame: 36 hours
measure: Maximum smoothed body weight standardized glucose infusion rate (GIRmax) and time to GIRmax (GIR-Tmax)
time frame: 36 hours
measure: Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different pre-specific blood glucose levels)
time frame: 4 days
measure: Safety and tolerability (Number of patients with adverse events, clinically significant changes in vital signs, laboratory parameters)
time frame: 4 days
arm group label: insulin glargine U100
arm group type: Active Comparator
description: 1 single dose
arm group label: insulin glargine U200
arm group type: Experimental
description: 1 single dose
arm group label: insulin glargine U500
arm group type: Experimental
description: 1 single dose
intervention type: Drug
intervention name: insulin glargine U200 HOE901
description: Pharmaceutical form:solution for injection Route of administration: subcutaneous
arm group label: insulin glargine U200
intervention type: Drug
intervention name: insulin glargine U500 HOE901
description: Pharmaceutical form:solution for injection Route of administration: subcutaneous
arm group label: insulin glargine U500
intervention type: Drug
intervention name: insulin glargine U100 HOE901
description: Pharmaceutical form:solution for injection Route of administration: subcutaneous
arm group label: insulin glargine U100
other name: Lantus
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Glargine