<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/NCT03292185</url>
  </required_header>
  <id_info>
    <org_study_id>NN9068-4139</org_study_id>
    <secondary_id>U1111-1155-0990</secondary_id>
    <nct_id>NCT03292185</nct_id>
  </id_info>
  <brief_title>A Trial to Investigate the Single Dose Pharmacokinetics of Insulin Degludec/Liraglutide Compared With Insulin Degludec and Liraglutide in Healthy Chinese Subjects</brief_title>
  <official_title>A Single Centre, Randomised, Double-blind, Three-period Cross-over Trial to Investigate the Single Dose Pharmacokinetics of Insulin Degludec/Liraglutide Compared With Insulin Degludec and Liraglutide in Healthy Chinese Subjects</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of the trial is to compare the bioavailability (extent of drug absorption&#xD;
      into the circulation) of insulin degludec and liraglutide as part of a combination product&#xD;
      insulin degludec/liraglutide compared to the corresponding doses of single, separate&#xD;
      injections of insulin degludec and liraglutide. Participants will receive all three test&#xD;
      substances. The order of trial administration will be allocated by chance. During the trial&#xD;
      period, serials of blood samples will be collected from the participants at three dosing&#xD;
      periods, in order to determine the concentration of insulin degludec and liraglutide. The&#xD;
      total volume of blood taken throughout the whole trial period will be less than 400 mL.&#xD;
      Participants will be asked to stay on daytime and overnight in the trial sites on some&#xD;
      predefined days. For other outpatient days, participants need to attend the trial site as&#xD;
      required for drug administration or required assessments.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 29, 2017</start_date>
  <completion_date type="Actual">January 2, 2018</completion_date>
  <primary_completion_date type="Actual">January 2, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Three-period complete cross-over, six treatment sequences</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Sponsor staff involved in the clinical trial is masked according to company standard procedures.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the serum insulin degludec concentration time curve</measure>
    <time_frame>From 0 to last quantifiable observation after single dose of insulin degludec/liraglutide and insulin degludec, assessments from 0 hours to 120 hours</time_frame>
    <description>Calculated based on insulin degludec concentration in serum</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma liraglutide concentration time curve</measure>
    <time_frame>from 0 to last quantifiable observation after single dose of insulin degludec/liraglutide and liraglutide, assessments from 0 hours to 72 hours</time_frame>
    <description>Calculated based on liraglutide concentration in plasma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the serum insulin degludec concentration time curve from 0 to infinity after single dose</measure>
    <time_frame>0 hours to 120 hours</time_frame>
    <description>Calculated based on insulin degludec measured in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed serum insulin degludec concentration</measure>
    <time_frame>0 hours to 120 hours</time_frame>
    <description>Calculated based on insulin degludec measured in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum serum insulin degludec concentration</measure>
    <time_frame>0 hours to 120 hours</time_frame>
    <description>Calculated based on insulin degludec measured in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life for insulin degludec</measure>
    <time_frame>0 hours to 120 hours</time_frame>
    <description>Calculated based on insulin degludec measured in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma liraglutide concentration time curve from 0 to infinity after single dose</measure>
    <time_frame>0 hours to 72 hours</time_frame>
    <description>Calculated based on liraglutide measured in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma liraglutide concentration</measure>
    <time_frame>0 hours to 72 hours</time_frame>
    <description>Calculated based on liraglutide measured in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum plasma liraglutide concentration</measure>
    <time_frame>0 hours to 72 hours</time_frame>
    <description>Calculated based on liraglutide measured in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life of liraglutide</measure>
    <time_frame>0 hours to 72 hours</time_frame>
    <description>Calculated based on liraglutide measured in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment emergent adverse events</measure>
    <time_frame>Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)</time_frame>
    <description>Count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment emergent hypoglycaemic episodes</measure>
    <time_frame>Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)</time_frame>
    <description>Count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local tolerability at the injection site</measure>
    <time_frame>Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)</time_frame>
    <description>Count</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Diabetes</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>IDeglira-IDeg-Liraglutide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment sequence first Insulin Degludec/Liraglutide, then Insulin Degludec, then Liraglutide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IDeglira-Liraglutide-IDeg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment sequence first Insulin Degludec/Liraglutide, then Liraglutide, then Insulin Degludec</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IDeg-Liraglutide-IDeglira</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment sequence first Isulin Degludec, then Liraglutide, then Insulin Degludec/Liraglutide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IDeg-IDeglira-Liraglutide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment sequence first Insulin Degludec, then Insulin Degludec/Liraglutide, then Liraglutide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liraglutide-IDeg-IDeglira</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment sequence first Liraglutide, then Insulin Degludec, then Insulin Degludec/Liraglutide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liraglutide-IDeglira-IDeg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment sequence first Liraglutide, then Insulin Degludec/Liraglutide, then Insulin Degludec</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin degludec/liraglutide</intervention_name>
    <description>Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.</description>
    <arm_group_label>IDeg-IDeglira-Liraglutide</arm_group_label>
    <arm_group_label>IDeg-Liraglutide-IDeglira</arm_group_label>
    <arm_group_label>IDeglira-IDeg-Liraglutide</arm_group_label>
    <arm_group_label>IDeglira-Liraglutide-IDeg</arm_group_label>
    <arm_group_label>Liraglutide-IDeg-IDeglira</arm_group_label>
    <arm_group_label>Liraglutide-IDeglira-IDeg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin degludec</intervention_name>
    <description>17 U Insulin Degludec, single dose administration under the skin in the thigh.</description>
    <arm_group_label>IDeg-IDeglira-Liraglutide</arm_group_label>
    <arm_group_label>IDeg-Liraglutide-IDeglira</arm_group_label>
    <arm_group_label>IDeglira-IDeg-Liraglutide</arm_group_label>
    <arm_group_label>IDeglira-Liraglutide-IDeg</arm_group_label>
    <arm_group_label>Liraglutide-IDeg-IDeglira</arm_group_label>
    <arm_group_label>Liraglutide-IDeglira-IDeg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>liraglutide</intervention_name>
    <description>0.6 mg Liraglutide, single dose administration under the skin in the thigh</description>
    <arm_group_label>IDeg-IDeglira-Liraglutide</arm_group_label>
    <arm_group_label>IDeg-Liraglutide-IDeglira</arm_group_label>
    <arm_group_label>IDeglira-IDeg-Liraglutide</arm_group_label>
    <arm_group_label>IDeglira-Liraglutide-IDeg</arm_group_label>
    <arm_group_label>Liraglutide-IDeg-IDeglira</arm_group_label>
    <arm_group_label>Liraglutide-IDeglira-IDeg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Male and female Chinese subjects, who are considered to be generally healthy, based on&#xD;
             assessment of medical history, physical examination, and clinical laboratory data, as&#xD;
             judged by the investigator&#xD;
&#xD;
          -  Age between 18 to 45 years (both inclusive) at the time of signing informed consent&#xD;
&#xD;
          -  Body mass index (BMI) between 19.0 and 24.0 kg/sqm (both inclusive)&#xD;
&#xD;
          -  Body weight at least 50.0 kg&#xD;
&#xD;
          -  Fasting plasma glucose less than 6.1 mmol/L (110 mg/dL)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Female who is pregnant, breast-feeding or intends to become pregnant or is of&#xD;
             child-bearing potential not using an adequate contraceptive methods throughout the&#xD;
             trial including follow-up period. Adequate contraceptive measures are sterilisation,&#xD;
             intrauterine device (IUD), oral contraceptives or barrier methods&#xD;
&#xD;
          -  Donation of any blood or plasma in the past month or in excess of 400 mL within the 90&#xD;
             days preceding screening or surgery or trauma with more than 400 mL blood loss within&#xD;
             the 90 days preceding screening&#xD;
&#xD;
          -  History or presence of cancer, or any clinically significant cardiovascular,&#xD;
             respiratory, metabolic, renal, hepatic, gastrointestinal, endocrine (incl. diabetes&#xD;
             and recurrent hypoglycaemia), haematological, dermatological, venereal, neurological,&#xD;
             psychiatric diseases or other major disorders that might have impact on the trial&#xD;
             result, as judged by the investigator&#xD;
&#xD;
          -  Use of any prescription or non-prescription medication, except for paracetamol,&#xD;
             acetylsalicylic acid, contraceptives and vitamins (mega-dose vitamin therapy not&#xD;
             allowed, dose judged by the investigator) within 2 weeks prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>November 15, 2019</last_update_submitted>
  <last_update_submitted_qc>November 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2019</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>Liraglutide</mesh_term>
    <mesh_term>Insulin, Long-Acting</mesh_term>
    <mesh_term>Xultophy</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>According to the Novo Nordisk disclosure commitment on novonordisk-trials.com</ipd_description>
  </patient_data>
  <!-- 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/NCT03292185
org study id: NN9068-4139
secondary id: U1111-1155-0990
nct id: NCT03292185
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The main purpose of the trial is to compare the bioavailability (extent of drug absorption
      into the circulation) of insulin degludec and liraglutide as part of a combination product
      insulin degludec/liraglutide compared to the corresponding doses of single, separate
      injections of insulin degludec and liraglutide. Participants will receive all three test
      substances. The order of trial administration will be allocated by chance. During the trial
      period, serials of blood samples will be collected from the participants at three dosing
      periods, in order to determine the concentration of insulin degludec and liraglutide. The
      total volume of blood taken throughout the whole trial period will be less than 400 mL.
      Participants will be asked to stay on daytime and overnight in the trial sites on some
      predefined days. For other outpatient days, participants need to attend the trial site as
      required for drug administration or required assessments.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Three-period complete cross-over, six treatment sequences
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
measure: Area under the serum insulin degludec concentration time curve
time frame: From 0 to last quantifiable observation after single dose of insulin degludec/liraglutide and insulin degludec, assessments from 0 hours to 120 hours
description: Calculated based on insulin degludec concentration in serum
measure: Area under the plasma liraglutide concentration time curve
time frame: from 0 to last quantifiable observation after single dose of insulin degludec/liraglutide and liraglutide, assessments from 0 hours to 72 hours
description: Calculated based on liraglutide concentration in plasma
measure: Area under the serum insulin degludec concentration time curve from 0 to infinity after single dose
time frame: 0 hours to 120 hours
description: Calculated based on insulin degludec measured in serum
measure: Maximum observed serum insulin degludec concentration
time frame: 0 hours to 120 hours
description: Calculated based on insulin degludec measured in serum
measure: Time to maximum serum insulin degludec concentration
time frame: 0 hours to 120 hours
description: Calculated based on insulin degludec measured in serum
measure: Terminal elimination half-life for insulin degludec
time frame: 0 hours to 120 hours
description: Calculated based on insulin degludec measured in serum
measure: Area under the plasma liraglutide concentration time curve from 0 to infinity after single dose
time frame: 0 hours to 72 hours
description: Calculated based on liraglutide measured in plasma
measure: Maximum observed plasma liraglutide concentration
time frame: 0 hours to 72 hours
description: Calculated based on liraglutide measured in plasma
measure: Time to maximum plasma liraglutide concentration
time frame: 0 hours to 72 hours
description: Calculated based on liraglutide measured in plasma
measure: Terminal elimination half-life of liraglutide
time frame: 0 hours to 72 hours
description: Calculated based on liraglutide measured in plasma
measure: Number of treatment emergent adverse events
time frame: Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)
description: Count
measure: Number of treatment emergent hypoglycaemic episodes
time frame: Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)
description: Count
measure: Local tolerability at the injection site
time frame: Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)
description: Count
arm group label: IDeglira-IDeg-Liraglutide
arm group type: Experimental
description: Treatment sequence first Insulin Degludec/Liraglutide, then Insulin Degludec, then Liraglutide
arm group label: IDeglira-Liraglutide-IDeg
arm group type: Experimental
description: Treatment sequence first Insulin Degludec/Liraglutide, then Liraglutide, then Insulin Degludec
arm group label: IDeg-Liraglutide-IDeglira
arm group type: Experimental
description: Treatment sequence first Isulin Degludec, then Liraglutide, then Insulin Degludec/Liraglutide
arm group label: IDeg-IDeglira-Liraglutide
arm group type: Experimental
description: Treatment sequence first Insulin Degludec, then Insulin Degludec/Liraglutide, then Liraglutide
arm group label: Liraglutide-IDeg-IDeglira
arm group type: Experimental
description: Treatment sequence first Liraglutide, then Insulin Degludec, then Insulin Degludec/Liraglutide
arm group label: Liraglutide-IDeglira-IDeg
arm group type: Experimental
description: Treatment sequence first Liraglutide, then Insulin Degludec/Liraglutide, then Insulin Degludec
intervention type: Drug
intervention name: insulin degludec/liraglutide
description: Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.
arm group label: IDeg-IDeglira-Liraglutide
arm group label: IDeg-Liraglutide-IDeglira
arm group label: IDeglira-IDeg-Liraglutide
arm group label: IDeglira-Liraglutide-IDeg
arm group label: Liraglutide-IDeg-IDeglira
arm group label: Liraglutide-IDeglira-IDeg
intervention type: Drug
intervention name: insulin degludec
description: 17 U Insulin Degludec, single dose administration under the skin in the thigh.
arm group label: IDeg-IDeglira-Liraglutide
arm group label: IDeg-Liraglutide-IDeglira
arm group label: IDeglira-IDeg-Liraglutide
arm group label: IDeglira-Liraglutide-IDeg
arm group label: Liraglutide-IDeg-IDeglira
arm group label: Liraglutide-IDeglira-IDeg
intervention type: Drug
intervention name: liraglutide
description: 0.6 mg Liraglutide, single dose administration under the skin in the thigh
arm group label: IDeg-IDeglira-Liraglutide
arm group label: IDeg-Liraglutide-IDeglira
arm group label: IDeglira-IDeg-Liraglutide
arm group label: IDeglira-Liraglutide-IDeg
arm group label: Liraglutide-IDeg-IDeglira
arm group label: Liraglutide-IDeglira-IDeg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Liraglutide
mesh term: Insulin, Long-Acting
mesh term: Xultophy
sharing ipd: Yes
ipd description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com