<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/NCT01730014</url>
  </required_header>
  <id_info>
    <org_study_id>NN1436-3955</org_study_id>
    <secondary_id>2011-005172-41</secondary_id>
    <secondary_id>U1111-1125-2924</secondary_id>
    <nct_id>NCT01730014</nct_id>
  </id_info>
  <brief_title>A Trial Investigating the Safety, Tolerability, and Distribution and Activity in the Body of NNC0148-0000-0287 Injected Under the Skin in Healthy Subjects and in Subjects With Type 1 Diabetes</brief_title>
  <official_title>A Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0148-0000-0287 in Healthy Subjects and in Subjects With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novo Nordisk A/S</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is conducted in Europe. The aim of this trial is to investigate safety,&#xD;
      tolerability, pharmacokinetics (the exposure of the trial drug in the body) and&#xD;
      pharmacodynamics (the effect of the investigated drug on the body) of subcutaneous&#xD;
      NNC0148-0000-0287 (insulin 287) in healthy subjects and in subjects with type 1 diabetes&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">July 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events (AE)</measure>
    <time_frame>From trial product administration until completion of the post-treatment follow-up visit at Day 37</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of hypoglycaemic episodes</measure>
    <time_frame>From trial product administration until completion of the post-treatment follow-up visit at Day 37</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC, the area under the serum insulin 287 concentration-time curve</measure>
    <time_frame>From dosing visit to infinity calculated from a 0-36 days NNC0148-0287 serum concentration-time-curve based on 43 sampling time points</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax, the maximum serum insulin 287 concentration</measure>
    <time_frame>Observed (within 0-36 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax, the time for maximum serum insulin 287 concentration</measure>
    <time_frame>Within 0-36 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average morning fasting blood glucose (FBG) concentration</measure>
    <time_frame>From Day 2 to Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average morning fasting serum C-peptide concentration</measure>
    <time_frame>From Day 2 to Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average morning fasting serum free fatty acid (FFA) concentration</measure>
    <time_frame>From Day 2 to Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the glucose infusion rate (GIR)-time curve</measure>
    <time_frame>At Day 1-2, 4-5, or 7-8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The maximal GIR (glucose infusion rate) observed</measure>
    <time_frame>At Day 1-2, 4-5, or 7-8</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Diabetes</condition>
  <condition>Diabetes Mellitus, Type 1</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Trial part 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Trial part 2, treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Trial part 2, treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>148-0287-A-4.2mM-cartridge</intervention_name>
    <description>In a dose-escalating design, healthy subjects will receive a single dose, injected subcutaneously.</description>
    <arm_group_label>Trial part 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>In a dose-escalating design, healthy subjects will receive 148-0287-A-placebo-cartridge, injected subcutaneously.</description>
    <arm_group_label>Trial part 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>148-0287-A-4.2mM-cartridge</intervention_name>
    <description>In a dose-escalating design, subjects with type 1 diabetes will receive a single dose, injected subcutaneously. Subjects will only be randomised to receive either treatment A or B.</description>
    <arm_group_label>Trial part 2, treatment A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>In a dose-escalating design, subjects with type 1 diabetes will receive 148-0287-A-placebo-cartridge in a single dose, injected subcutaneously. Subjects will only be randomised to receive either treatment A or B.</description>
    <arm_group_label>Trial part 2, treatment B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin glargine</intervention_name>
    <description>In a dose-escalating design, subjects with type 1 diabetes will receive insulin glargine once daily, injected subcutaneously. Subjects will only be randomised to receive either treatment A or B.</description>
    <arm_group_label>Trial part 2, treatment B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sodium chloride 0.9% w/v</intervention_name>
    <description>In a dose-escalating design, subjects with type 1 diabetes will receive sodium chloride 0.9% w/v, injected subcutaneously daily. Subjects will only be randomised to receive either treatment A or B.</description>
    <arm_group_label>Trial part 2, treatment A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  TRIAL PART 1 (HEALTHY SUBJECTS):&#xD;
&#xD;
          -  Healthy male subject&#xD;
&#xD;
          -  Age 18-55 years (both inclusive)&#xD;
&#xD;
          -  Body mass index 18.0-28.0 kg/m^2 (both inclusive)&#xD;
&#xD;
          -  TRIAL PART 2 (SUBJECTS WITH TYPE 1 DIABETES):&#xD;
&#xD;
          -  Healthy male subject (with the exception of conditions associated with diabetes&#xD;
             mellitus)&#xD;
&#xD;
          -  Age 18-64 years (both inclusive)&#xD;
&#xD;
          -  Body mass index 18.0-28.0 kg/m^2 (both incl.)&#xD;
&#xD;
          -  Type 1 diabetes mellitus (as diagnosed clinically) and treated with multiple daily&#xD;
             insulin injections more than 12 months&#xD;
&#xD;
          -  HbA1C (glycosylated haemoglobin) below or equal to 8.5 %&#xD;
&#xD;
          -  Current daily basal insulin requirement above or equal to 0.2 to below or equal to 0.8&#xD;
             (I)U/kg/day and current total daily insulin treatment below 1.2 (I)U/kg/day&#xD;
&#xD;
          -  Fasting C-peptide below 0.3 nmol/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The receipt of any investigational medicinal product within the last 3 months prior to&#xD;
             the start of this trial (screening)&#xD;
&#xD;
          -  Significant blood loss (due to donation, surgery or trauma) of more than 500 mL within&#xD;
             3 months prior to the start of this trial (screening) or participating in any other&#xD;
             trial involving blood sampling within the last 2 months before the start of this trial&#xD;
             (screening)&#xD;
&#xD;
          -  Use of any prescription (see specification below for Trial Part 2) or non-prescription&#xD;
             medication, including herbal products and non-routine vitamins, within the last 2&#xD;
             weeks before the start of the trial (screening) that will interfere with the&#xD;
             pharmacokinetics of insulin 287, as judged by the investigator in agreement with the&#xD;
             sponsor. Routine vitamins and occasional use judged by the investigator in agreement&#xD;
             with the sponsor. Routine vitamins and occasional use of paracetamol is permitted up&#xD;
             to 48 hours prior to dosing&#xD;
&#xD;
          -  History of alcoholism or drug abuse (within the last 2 years), or positive result of&#xD;
             alcohol or drug screening test&#xD;
&#xD;
          -  Currently smoke more than 1 cigarette per day (or the equivalent for other tobacco&#xD;
             products) or smoking 1 cigarette or less per day and not considering being able to&#xD;
             refrain from smoking or refrain from use of other types of nicotine products (e.g.&#xD;
             such as chewing tobacco, nicotine gums) during the in-house periods&#xD;
&#xD;
          -  Habitual excessive consumption of methylxanthine-containing (theophylline, caffeine or&#xD;
             theobromine) beverages and foods (coffee, tea, soft drinks such as red bull, cola,&#xD;
             chocolate) as judged by the investigator&#xD;
&#xD;
          -  Excessive consumption of a diet deviating from a normal diet as judged by the&#xD;
             investigator&#xD;
&#xD;
          -  Mental incapacity, unwillingness or language barriers precluding adequate&#xD;
             understanding or cooperation in the trial&#xD;
&#xD;
          -  Vulnerable subjects (e.g. persons kept in detention)&#xD;
&#xD;
          -  Subject is the investigator or any sub-investigator, research assistant, pharmacist,&#xD;
             study coordinator, other staff or relative thereof directly involved in the conduct of&#xD;
             the trial&#xD;
&#xD;
          -  ADDITIONAL KEY EXCLUSION CRITERIA TRIAL PART 2 (subjects with type 1 diabetes):&#xD;
&#xD;
          -  Current treatment with statins, systemic (oral, intravenous or inhaled)&#xD;
             corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers,&#xD;
             thyroid hormones, growth hormone and other drugs, which may interfere with glucose&#xD;
             metabolism&#xD;
&#xD;
          -  Increased risk of thrombosis, e.g. subjects with a history of deep leg vein thrombosis&#xD;
             or family history of deep leg vein thrombosis, as judged by the investigator&#xD;
&#xD;
          -  Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last&#xD;
             12 months) or hypoglycaemic unawareness as judged by the Investigator or&#xD;
             hospitalisation for diabetic ketoacidosis during the past 6 months before start of&#xD;
             this trial (screening)&#xD;
&#xD;
          -  Cardiac problems defined as: decompensated heart failure (New York Heart Association&#xD;
             (NYHA) class III and IV) at any time, or acute myocardial infarction at any time, or&#xD;
             angina pectoris within the last 12 months before start of this trial (screening)&#xD;
&#xD;
          -  Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular&#xD;
             autonomic neuropathy, as judged by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Registry (GCR, 1452)</last_name>
    <role>Study Director</role>
    <affiliation>Novo Nordisk A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Neuss</city>
        <zip>41460</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://novonordisk-trials.com</url>
    <description>Clinical Trials at Novo Nordisk</description>
  </link>
  <verification_date>July 2013</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>July 30, 2013</last_update_submitted>
  <last_update_submitted_qc>July 30, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 31, 2013</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 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/NCT01730014
org study id: NN1436-3955
secondary id: 2011-005172-41
secondary id: U1111-1125-2924
nct id: NCT01730014
lead sponsor: 
has dmc: No
This trial is conducted in Europe. The aim of this trial is to investigate safety,
      tolerability, pharmacokinetics (the exposure of the trial drug in the body) and
      pharmacodynamics (the effect of the investigated drug on the body) of subcutaneous
      NNC0148-0000-0287 (insulin 287) in healthy subjects and in subjects with type 1 diabetes
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence of adverse events (AE)
time frame: From trial product administration until completion of the post-treatment follow-up visit at Day 37
measure: Incidence of hypoglycaemic episodes
time frame: From trial product administration until completion of the post-treatment follow-up visit at Day 37
measure: AUC, the area under the serum insulin 287 concentration-time curve
time frame: From dosing visit to infinity calculated from a 0-36 days NNC0148-0287 serum concentration-time-curve based on 43 sampling time points
measure: Cmax, the maximum serum insulin 287 concentration
time frame: Observed (within 0-36 days)
measure: tmax, the time for maximum serum insulin 287 concentration
time frame: Within 0-36 days
measure: Average morning fasting blood glucose (FBG) concentration
time frame: From Day 2 to Day 8
measure: Average morning fasting serum C-peptide concentration
time frame: From Day 2 to Day 8
measure: Average morning fasting serum free fatty acid (FFA) concentration
time frame: From Day 2 to Day 8
measure: Area under the glucose infusion rate (GIR)-time curve
time frame: At Day 1-2, 4-5, or 7-8
measure: The maximal GIR (glucose infusion rate) observed
time frame: At Day 1-2, 4-5, or 7-8
arm group label: Trial part 1
arm group type: Experimental
arm group label: Trial part 2, treatment A
arm group type: Experimental
arm group label: Trial part 2, treatment B
arm group type: Experimental
intervention type: Drug
intervention name: 148-0287-A-4.2mM-cartridge
description: In a dose-escalating design, healthy subjects will receive a single dose, injected subcutaneously.
arm group label: Trial part 1
intervention type: Drug
intervention name: placebo
description: In a dose-escalating design, healthy subjects will receive 148-0287-A-placebo-cartridge, injected subcutaneously.
arm group label: Trial part 1
intervention type: Drug
intervention name: 148-0287-A-4.2mM-cartridge
description: In a dose-escalating design, subjects with type 1 diabetes will receive a single dose, injected subcutaneously. Subjects will only be randomised to receive either treatment A or B.
arm group label: Trial part 2, treatment A
intervention type: Drug
intervention name: placebo
description: In a dose-escalating design, subjects with type 1 diabetes will receive 148-0287-A-placebo-cartridge in a single dose, injected subcutaneously. Subjects will only be randomised to receive either treatment A or B.
arm group label: Trial part 2, treatment B
intervention type: Drug
intervention name: insulin glargine
description: In a dose-escalating design, subjects with type 1 diabetes will receive insulin glargine once daily, injected subcutaneously. Subjects will only be randomised to receive either treatment A or B.
arm group label: Trial part 2, treatment B
intervention type: Drug
intervention name: sodium chloride 0.9% w/v
description: In a dose-escalating design, subjects with type 1 diabetes will receive sodium chloride 0.9% w/v, injected subcutaneously daily. Subjects will only be randomised to receive either treatment A or B.
arm group label: Trial part 2, treatment A
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Global Clinical Registry (GCR, 1452)
role: Study Director
affiliation: Novo Nordisk A/S
facility: 
country: Germany
url: http://novonordisk-trials.com
description: Clinical Trials at Novo Nordisk
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin Glargine