<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/NCT01697657</url>
  </required_header>
  <id_info>
    <org_study_id>NN304-1375</org_study_id>
    <nct_id>NCT01697657</nct_id>
  </id_info>
  <brief_title>Frequency of Hypoglycaemic Episodes During Treatment With Insulin Detemir in Well Controlled Subjects With Type 1 Diabetes</brief_title>
  <official_title>A Randomised, Open Label, Cross-over, Multi-centre, Multinational Trial Comparing the Frequency of Hypoglycaemic Episodes During Treatment With Insulin Detemir and NPH Insulin in Well Controlled Subjects With Type 1 Diabetes on a Basal-bolus Regimen</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 Africa, Europe and Oceania. The aim of this trial is to&#xD;
      investigate whether insulin detemir combined with insulin aspart compared to NPH insulin&#xD;
      combined with insulin aspart could reduce the frequency of hypoglycaemic episodes whilst&#xD;
      maintaining the same degree of glycaemic control subjects with type 1 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2001</start_date>
  <completion_date type="Actual">November 2002</completion_date>
  <primary_completion_date type="Actual">November 2002</primary_completion_date>
  <phase>Phase 3</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of total self-recorded hypoglycaemic episodes</measure>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of total major hypoglycaemic episodes</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c (glycosylated haemoglobin)</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>8-point plasma glucose profiles</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum glucose profiles</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>72-hours glucose profile</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Within-subject variation in home-measured fasting plasma glucose</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">131</enrollment>
  <condition>Diabetes</condition>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Detemir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NPH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin detemir</intervention_name>
    <description>Subjects were dosed according to individual requirements. Injected subcutaneously (s.c. under the skin) twice daily in the morning and at bedtime for 10 weeks after an initial 6-week titration in treatment period 1 followed by 10 weeks after an initial 6-week titration in treatment period 2</description>
    <arm_group_label>Detemir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin NPH</intervention_name>
    <description>Subjects were dosed according to individual requirements. Injected subcutaneously (s.c. under the skin) twice daily in the morning and at bedtime for 10 weeks after an initial 6-week titration in treatment period 1 followed by 10 weeks after an initial 6-week titration in treatment period 2</description>
    <arm_group_label>NPH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin aspart</intervention_name>
    <description>Subjects were dosed according to individual requirements. Injected subcutaneously (s.c. under the skin) twice daily before meals for 10 weeks after an initial 6-week titration in treatment period 1 followed by 10 weeks after an initial 6-week titration in treatment period 2</description>
    <arm_group_label>Detemir</arm_group_label>
    <arm_group_label>NPH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Fasting c-peptide below lower limit of normal fasting range&#xD;
&#xD;
          -  Duration of type 1 diabetes for at least 12 months&#xD;
&#xD;
          -  Current treatment: Basal - bolus regimen for at least 4 months with intermediate or&#xD;
             long-acting insulin once, twice or three times daily as basal insulin and 3-4 premeal&#xD;
             insulin aspart or lispro injections&#xD;
&#xD;
          -  HbA1c maximum 9.0% (using Biorad Variant method)&#xD;
&#xD;
          -  Able and willing to perform self-monitoring of blood glucose&#xD;
&#xD;
          -  Basal insulin requirement at least 30% of the total daily insulin dose&#xD;
&#xD;
          -  BMI (body Mass Index) maximum 35 kg/m^2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Proliferative retinopathy or maculopathy requiring acute treatment&#xD;
&#xD;
          -  Total daily insulin dose above 1.4 IU/kg/day&#xD;
&#xD;
          -  Known unawareness of hypoglycaemia&#xD;
&#xD;
          -  Impaired hepatic function&#xD;
&#xD;
          -  Impaired renal function&#xD;
&#xD;
          -  Cardiac problems&#xD;
&#xD;
          -  Uncontrolled, treated/untreated hypertension&#xD;
&#xD;
          -  Known or suspected allergy to trial product or related products&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</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>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ashford</city>
        <zip>5035</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Box Hill</city>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Zagreb</city>
        <zip>10 000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Køge</city>
        <zip>4600</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Århus C</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Citta' Di Castello</city>
        <zip>06012</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Perugia</city>
        <zip>06126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7925</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Linköping</city>
        <zip>581 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Trelleborg</city>
        <zip>231 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Croatia</country>
    <country>Denmark</country>
    <country>Italy</country>
    <country>South Africa</country>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://novonordisk-trials.com</url>
    <description>Clinical Trials at Novo Nordisk</description>
  </link>
  <results_reference>
    <citation>Kolendorf K, Ross GP, Pavlic-Renar I, Perriello G, Philotheou A, Jendle J, Gall MA, Heller SR. Insulin detemir lowers the risk of hypoglycaemia and provides more consistent plasma glucose levels compared with NPH insulin in Type 1 diabetes. Diabet Med. 2006 Jul;23(7):729-35. doi: 10.1111/j.1464-5491.2006.01862.x.</citation>
    <PMID>16842476</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>January 26, 2017</last_update_submitted>
  <last_update_submitted_qc>January 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 27, 2017</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 Aspart</mesh_term>
    <mesh_term>Insulin Detemir</mesh_term>
    <mesh_term>Isophane Insulin, Human</mesh_term>
    <mesh_term>Insulin, Isophane</mesh_term>
    <mesh_term>Isophane insulin, beef</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/NCT01697657
org study id: NN304-1375
nct id: NCT01697657
lead sponsor: 
has dmc: No
This trial is conducted in Africa, Europe and Oceania. The aim of this trial is to
      investigate whether insulin detemir combined with insulin aspart compared to NPH insulin
      combined with insulin aspart could reduce the frequency of hypoglycaemic episodes whilst
      maintaining the same degree of glycaemic control subjects with type 1 diabetes.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of total self-recorded hypoglycaemic episodes
measure: Incidence of total major hypoglycaemic episodes
measure: HbA1c (glycosylated haemoglobin)
measure: 8-point plasma glucose profiles
measure: Serum glucose profiles
measure: 72-hours glucose profile
measure: Within-subject variation in home-measured fasting plasma glucose
measure: Incidence of adverse events
arm group label: Detemir
arm group type: Experimental
arm group label: NPH
arm group type: Active Comparator
intervention type: Drug
intervention name: insulin detemir
description: Subjects were dosed according to individual requirements. Injected subcutaneously (s.c. under the skin) twice daily in the morning and at bedtime for 10 weeks after an initial 6-week titration in treatment period 1 followed by 10 weeks after an initial 6-week titration in treatment period 2
arm group label: Detemir
intervention type: Drug
intervention name: insulin NPH
description: Subjects were dosed according to individual requirements. Injected subcutaneously (s.c. under the skin) twice daily in the morning and at bedtime for 10 weeks after an initial 6-week titration in treatment period 1 followed by 10 weeks after an initial 6-week titration in treatment period 2
arm group label: NPH
intervention type: Drug
intervention name: insulin aspart
description: Subjects were dosed according to individual requirements. Injected subcutaneously (s.c. under the skin) twice daily before meals for 10 weeks after an initial 6-week titration in treatment period 1 followed by 10 weeks after an initial 6-week titration in treatment period 2
arm group label: Detemir
arm group label: NPH
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Global Clinical Registry (GCR, 1452)
role: Study Director
affiliation: Novo Nordisk A/S
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Croatia
country: Denmark
country: Italy
country: South Africa
country: Sweden
url: http://novonordisk-trials.com
description: Clinical Trials at Novo Nordisk
citation: Kolendorf K, Ross GP, Pavlic-Renar I, Perriello G, Philotheou A, Jendle J, Gall MA, Heller SR. Insulin detemir lowers the risk of hypoglycaemia and provides more consistent plasma glucose levels compared with NPH insulin in Type 1 diabetes. Diabet Med. 2006 Jul;23(7):729-35. doi: 10.1111/j.1464-5491.2006.01862.x.
PMID: 16842476
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 Aspart
mesh term: Insulin Detemir
mesh term: Isophane Insulin, Human
mesh term: Insulin, Isophane
mesh term: Isophane insulin, beef