<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/NCT01680341</url>
  </required_header>
  <id_info>
    <org_study_id>NN5401-3941</org_study_id>
    <secondary_id>2012-000373-23</secondary_id>
    <secondary_id>U1111-1127-4114</secondary_id>
    <nct_id>NCT01680341</nct_id>
  </id_info>
  <brief_title>Comparison of the Efficacy and Safety of Two Different Dose Adjustment Regimens for Insulin Degludec/Insulin Aspart in Subjects With Type 2 Diabetes Mellitus Previously Treated With Insulin Glargine</brief_title>
  <acronym>BOOST®</acronym>
  <official_title>A Trial Comparing the Efficacy and Safety of Two Different Titration Algorithms for Insulin Degludec/Insulin Aspart in Subjects With Type 2 Diabetes Mellitus Previously Treated With Insulin Glargine (BOOST®: SIMPLE vs. STEPWISE)</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, Asia, Europe and the United States of America (USA).&#xD;
&#xD;
      The aim of the trial is to compare the efficacy and safety of two different titration&#xD;
      algorithms for insulin degludec/insulin aspart (IDeg/IAsp) in subjects with type 2 diabetes&#xD;
      mellitus previously treated with insulin glargine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2012</start_date>
  <completion_date type="Actual">August 22, 2013</completion_date>
  <primary_completion_date type="Actual">August 22, 2013</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)</measure>
    <time_frame>Week 0, Week 26</time_frame>
    <description>Change from baseline in HbA1c after 26 weeks of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Fasting Plasma Glucose (FPG)</measure>
    <time_frame>Week 0, Week 26</time_frame>
    <description>Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjects With HbA1c Below 7.0%</measure>
    <time_frame>Week 26</time_frame>
    <description>Number of subjects with HbA1c below 7% after 26 weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia</measure>
    <time_frame>Week 26</time_frame>
    <description>Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Weeks 0-28</time_frame>
    <description>A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment Emergent Confirmed Hypoglycaemic Episodes</measure>
    <time_frame>Weeks 0-27</time_frame>
    <description>Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period</measure>
    <time_frame>From week 16 to end of trial including follow-up (week 27)</time_frame>
    <description>Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up [Week 27]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes</measure>
    <time_frame>Weeks 0-27</time_frame>
    <description>Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 am.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">272</enrollment>
  <condition>Diabetes</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>IDegAsp Simple</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>IDegAsp Step wise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin degludec/insulin aspart</intervention_name>
    <description>Twice weekly self-titration at intervals of 3-4 days, based upon a single pre-breakfast and pre-dinner SMPG (self-measured plasma glucose) value. For subcutaneous (s.c., under the skin) administration.</description>
    <arm_group_label>IDegAsp Simple</arm_group_label>
    <other_name>IDegAsp</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin degludec/insulin aspart</intervention_name>
    <description>Once weekly self-titration based upon the lowest of 3 pre-breakfast and 3 pre-dinner SMPG (self-measured plasma glucose) values. For subcutaneous (s.c., under the skin) administration.</description>
    <arm_group_label>IDegAsp Step wise</arm_group_label>
    <other_name>IDegAsp</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes (diagnosed clinically) for at least 24 weeks prior to Visit 2&#xD;
             (randomisation)&#xD;
&#xD;
          -  Currently treated with IGlar (Insulin Glargine) and up to 3 oral antidiabetic drugs&#xD;
             (OADs) (metformin, DPP-4 inhibitor, sulphonylurea/glinide or alpha-glucosidase&#xD;
             inhibitor). All antidiabetic treatments should have been ongoing for at least 12 weeks&#xD;
             prior to Visit 2 (randomisation) and doses should have been stable in this period of&#xD;
             time&#xD;
&#xD;
          -  Glycosylated haemoglobin (HbA1c) 7.0-10.0% (both inclusive) by central laboratory&#xD;
             analysis&#xD;
&#xD;
          -  Body mass index (BMI) below or equal to 40 kg/m^2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists or thiazolidinediones&#xD;
             (TZDs) both within the last 12 weeks prior to Visit 2 (randomisation)&#xD;
&#xD;
          -  Stroke; heart failure New York Heart Association (NYHA) class III or IV; myocardial&#xD;
             infarction; unstable angina pectoris; or coronary arterial bypass graft or&#xD;
             angioplasty; all within the last 24 weeks prior to Visit 2 (randomisation)&#xD;
&#xD;
          -  Uncontrolled or untreated severe hypertension defined as systolic blood pressure above&#xD;
             or equal to 180 mmHg and/or diastolic blood pressure above or equal to 100 mmHg&#xD;
&#xD;
          -  Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during last 12&#xD;
             months) or hypoglycaemic unawareness as judged by the investigator&#xD;
&#xD;
          -  Life-threatening disease (e.g. cancer)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</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>Goodyear</city>
        <state>Arizona</state>
        <zip>85395</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Greenbrae</city>
        <state>California</state>
        <zip>94904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Spring Valley</city>
        <state>California</state>
        <zip>91978</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kissimmee</city>
        <state>Florida</state>
        <zip>34741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Suwanee</city>
        <state>Georgia</state>
        <zip>30024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Avon</city>
        <state>Illinois</state>
        <zip>46123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Crystal Lake</city>
        <state>Illinois</state>
        <zip>60012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46254</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Slidell</city>
        <state>Louisiana</state>
        <zip>70461-4231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Waltham</city>
        <state>Massachusetts</state>
        <zip>02453</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Buckley</city>
        <state>Michigan</state>
        <zip>49620</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nashua</city>
        <state>New Hampshire</state>
        <zip>03063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lawrenceville</city>
        <state>New Jersey</state>
        <zip>08648</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755-8050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29572</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75251</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Olympia</city>
        <state>Washington</state>
        <zip>98502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kenosha</city>
        <state>Wisconsin</state>
        <zip>53144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Algiers</city>
        <zip>16000</zip>
        <country>Algeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Oran</city>
        <zip>31000</zip>
        <country>Algeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tizi Ouzou</city>
        <zip>16015</zip>
        <country>Algeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Erdmannhausen</city>
        <zip>71729</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Münster</city>
        <zip>48145</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Neuwied</city>
        <zip>56564</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Pohlheim</city>
        <zip>35415</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Rehlingen-Siersburg</city>
        <zip>66780</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint Ingbert</city>
        <zip>66386</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Cheras</city>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kota Bharu, Kelantan</city>
        <zip>16150</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Selangor</city>
        <zip>46150</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Antalya</city>
        <zip>07050</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Denizli</city>
        <zip>20070</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Gaziantep</city>
        <zip>27070</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hatay</city>
        <zip>31040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Istanbul</city>
        <zip>34752</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Algeria</country>
    <country>Germany</country>
    <country>Malaysia</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://novonordisk-trials.com</url>
    <description>Clinical Trials at Novo Nordisk</description>
  </link>
  <results_reference>
    <citation>Bode BW, Buse JB, Fisher M, Garg SK, Marre M, Merker L, Renard E, Russell-Jones DL, Hansen CT, Rana A, Heller SR; BEGIN(R) Basal-Bolus Type 1 trial investigators. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN((R)) Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med. 2013 Nov;30(11):1293-7. doi: 10.1111/dme.12243. Epub 2013 Jun 17.</citation>
    <PMID>23710902</PMID>
  </results_reference>
  <results_reference>
    <citation>Haluzik M, Fulcher G, Pieber TR, Bardtrum L, Tutkunkardas D, Rodbard HW. The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes. Diabetes Obes Metab. 2018 Jul;20(7):1585-1592. doi: 10.1111/dom.13261. Epub 2018 Mar 25.</citation>
    <PMID>29451706</PMID>
  </results_reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <results_first_submitted>October 16, 2015</results_first_submitted>
  <results_first_submitted_qc>October 16, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 17, 2015</results_first_posted>
  <disposition_first_submitted>November 7, 2013</disposition_first_submitted>
  <disposition_first_submitted_qc>November 7, 2013</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">December 2, 2013</disposition_first_posted>
  <last_update_submitted>March 6, 2018</last_update_submitted>
  <last_update_submitted_qc>March 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2018</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 2</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, Long-Acting</mesh_term>
    <mesh_term>Insulin degludec, insulin aspart drug combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The trial was conducted in 43 sites in 5 countries: Algeria (3 sites), Germany (5 sites), Malaysia (3 sites), Turkey (3 sites), and United States (29 sites).</recruitment_details>
      <pre_assignment_details>While entering the treatment period the subjects discontinued insulin glargine (IGlar) and sulfonylurea (SU)/glinides (if administered) but continued treatment with up to 3 other oral antidiabetic drugs (OADs) as prescribed.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>IDegAsp Simple</title>
          <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
        </group>
        <group group_id="P2">
          <title>IDegAsp Step Wise</title>
          <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="136"/>
                <participants group_id="P2" count="136"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Exposed</title>
              <participants_list>
                <participants group_id="P1" count="135">One (1) subject withdrew consent prior to exposure to trial product.</participants>
                <participants group_id="P2" count="134">Two (2) subjects withdrew consent prior to exposure to trial product.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="115"/>
                <participants group_id="P2" count="119"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unclassified</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>IDegAsp Simple</title>
          <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
        </group>
        <group group_id="B2">
          <title>IDegAsp Step Wise</title>
          <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="136"/>
            <count group_id="B2" value="136"/>
            <count group_id="B3" value="272"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.8" spread="9.8"/>
                    <measurement group_id="B2" value="59.1" spread="9.4"/>
                    <measurement group_id="B3" value="58.9" spread="9.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="113"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Glycosylated Haemoglobin (HbA1c)</title>
          <units>percentage of glycosylated haemoglobin</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.2" spread="0.9"/>
                    <measurement group_id="B2" value="8.2" spread="0.9"/>
                    <measurement group_id="B3" value="8.2" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fasting plasma glucose</title>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.8" spread="2.3"/>
                    <measurement group_id="B2" value="8.1" spread="3.0"/>
                    <measurement group_id="B3" value="8.0" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)</title>
        <description>Change from baseline in HbA1c after 26 weeks of treatment.</description>
        <time_frame>Week 0, Week 26</time_frame>
        <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)</title>
          <description>Change from baseline in HbA1c after 26 weeks of treatment.</description>
          <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF).</population>
          <units>Percent (%) glycosylated haemoglobin</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="136"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.45" spread="0.09"/>
                    <measurement group_id="O2" value="-1.33" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Fasting Plasma Glucose (FPG)</title>
        <description>Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment</description>
        <time_frame>Week 0, Week 26</time_frame>
        <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Fasting Plasma Glucose (FPG)</title>
          <description>Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment</description>
          <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.</population>
          <units>mmol/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="136"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.68" spread="0.23"/>
                    <measurement group_id="O2" value="-1.98" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subjects With HbA1c Below 7.0%</title>
        <description>Number of subjects with HbA1c below 7% after 26 weeks of treatment.</description>
        <time_frame>Week 26</time_frame>
        <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Subjects With HbA1c Below 7.0%</title>
          <description>Number of subjects with HbA1c below 7% after 26 weeks of treatment.</description>
          <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.</population>
          <units>Subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="136"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia</title>
        <description>Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment.</description>
        <time_frame>Week 26</time_frame>
        <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF. Twenty five (25) subjects did not contribute to statistical analysis as Endpoint was only defined for subjects exposed for at least 12 treatment weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia</title>
          <description>Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment.</description>
          <population>The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF. Twenty five (25) subjects did not contribute to statistical analysis as Endpoint was only defined for subjects exposed for at least 12 treatment weeks.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="125"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.4"/>
                    <measurement group_id="O2" value="32.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Treatment Emergent Adverse Events (TEAEs)</title>
        <description>A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.</description>
        <time_frame>Weeks 0-28</time_frame>
        <population>The safety analysis set included all subjects who received at least one dose of the investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Treatment Emergent Adverse Events (TEAEs)</title>
          <description>A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.</description>
          <population>The safety analysis set included all subjects who received at least one dose of the investigational product.</population>
          <units>number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="135"/>
                <count group_id="O2" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="242"/>
                    <measurement group_id="O2" value="286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment Emergent Confirmed Hypoglycaemic Episodes</title>
        <description>Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.</description>
        <time_frame>Weeks 0-27</time_frame>
        <population>The safety analysis set included all subjects who received at least one dose of the investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment Emergent Confirmed Hypoglycaemic Episodes</title>
          <description>Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.</description>
          <population>The safety analysis set included all subjects who received at least one dose of the investigational product.</population>
          <units>episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="135"/>
                <count group_id="O2" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="552"/>
                    <measurement group_id="O2" value="323"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period</title>
        <description>Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up [Week 27]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.</description>
        <time_frame>From week 16 to end of trial including follow-up (week 27)</time_frame>
        <population>The safety analysis set included all subjects who received at least one dose of the investigational product. Subjects in maintenance period were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period</title>
          <description>Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up [Week 27]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.</description>
          <population>The safety analysis set included all subjects who received at least one dose of the investigational product. Subjects in maintenance period were included in this analysis.</population>
          <units>episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="121"/>
                <count group_id="O2" value="124"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="230"/>
                    <measurement group_id="O2" value="143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes</title>
        <description>Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 am.</description>
        <time_frame>Weeks 0-27</time_frame>
        <population>The safety analysis set included all subjects who received at least one dose of the investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>IDegAsp Simple</title>
            <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
          </group>
          <group group_id="O2">
            <title>IDegAsp Step Wise</title>
            <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes</title>
          <description>Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 am.</description>
          <population>The safety analysis set included all subjects who received at least one dose of the investigational product.</population>
          <units>episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="135"/>
                <count group_id="O2" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The adverse events were collected from week 0 to Week 28.</time_frame>
      <desc>The safety analysis set included all subjects who received at least one dose of the investigational product.</desc>
      <group_list>
        <group group_id="E1">
          <title>IDegAsp Simple</title>
          <description>Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value.</description>
        </group>
        <group group_id="E2">
          <title>IDegAsp Step Wise</title>
          <description>IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Aortic valve stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess limb</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Pulmonary arterial hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="53" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="135"/>
                <counts group_id="E2" events="12" subjects_affected="8" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="135"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="135"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="16" subjects_affected="12" subjects_at_risk="135"/>
                <counts group_id="E2" events="23" subjects_affected="20" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="135"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="135"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="135"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Public Access to Clinical Trials</name_or_title>
      <organization>Novo Nordisk A/S</organization>
      <email>clinicaltrials@novonordisk.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01680341
org study id: NN5401-3941
secondary id: 2012-000373-23
secondary id: U1111-1127-4114
nct id: NCT01680341
lead sponsor: 
has dmc: No
This trial is conducted in Africa, Asia, Europe and the United States of America (USA).

      The aim of the trial is to compare the efficacy and safety of two different titration
      algorithms for insulin degludec/insulin aspart (IDeg/IAsp) in subjects with type 2 diabetes
      mellitus previously treated with insulin glargine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)
time frame: Week 0, Week 26
description: Change from baseline in HbA1c after 26 weeks of treatment.
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
time frame: Week 0, Week 26
description: Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment
measure: Subjects With HbA1c Below 7.0%
time frame: Week 26
description: Number of subjects with HbA1c below 7% after 26 weeks of treatment.
measure: Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia
time frame: Week 26
description: Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment.
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
time frame: Weeks 0-28
description: A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
measure: Number of Treatment Emergent Confirmed Hypoglycaemic Episodes
time frame: Weeks 0-27
description: Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
measure: Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period
time frame: From week 16 to end of trial including follow-up (week 27)
description: Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up [Week 27]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
measure: Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes
time frame: Weeks 0-27
description: Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 am.
arm group label: IDegAsp Simple
arm group type: Experimental
arm group label: IDegAsp Step wise
arm group type: Experimental
intervention type: Drug
intervention name: insulin degludec/insulin aspart
description: Twice weekly self-titration at intervals of 3-4 days, based upon a single pre-breakfast and pre-dinner SMPG (self-measured plasma glucose) value. For subcutaneous (s.c., under the skin) administration.
arm group label: IDegAsp Simple
other name: IDegAsp
intervention type: Drug
intervention name: insulin degludec/insulin aspart
description: Once weekly self-titration based upon the lowest of 3 pre-breakfast and 3 pre-dinner SMPG (self-measured plasma glucose) values. For subcutaneous (s.c., under the skin) administration.
arm group label: IDegAsp Step wise
other name: IDegAsp
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Registry (GCR, 1452)
role: Study Director
affiliation: Novo Nordisk A/S
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country: Algeria
country: Germany
country: Malaysia
country: Turkey
country: United States
url: http://novonordisk-trials.com
description: Clinical Trials at Novo Nordisk
citation: Bode BW, Buse JB, Fisher M, Garg SK, Marre M, Merker L, Renard E, Russell-Jones DL, Hansen CT, Rana A, Heller SR; BEGIN(R) Basal-Bolus Type 1 trial investigators. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN((R)) Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med. 2013 Nov;30(11):1293-7. doi: 10.1111/dme.12243. Epub 2013 Jun 17.
PMID: 23710902
citation: Haluzik M, Fulcher G, Pieber TR, Bardtrum L, Tutkunkardas D, Rodbard HW. The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes. Diabetes Obes Metab. 2018 Jul;20(7):1585-1592. doi: 10.1111/dom.13261. Epub 2018 Mar 25.
PMID: 29451706
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Aspart
mesh term: Insulin, Long-Acting
mesh term: Insulin degludec, insulin aspart drug combination
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 