<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/NCT03288740</url>
  </required_header>
  <id_info>
    <org_study_id>NN9535-3686</org_study_id>
    <secondary_id>U1111-1149-6572</secondary_id>
    <nct_id>NCT03288740</nct_id>
  </id_info>
  <brief_title>A Trial to Assess the Pharmacokinetics, Safety and Tolerability of Semaglutide in Healthy Chinese Subjects</brief_title>
  <official_title>A Single-centre, Randomised, Double-blind, Placebo-controlled, Multiple-dose Trial to Assess the Pharmacokinetics, Safety and Tolerability of Semaglutide 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 assess the pharmacokinetics of semaglutide (i.e. the way&#xD;
      the drug is distributed in the body over a period of time) following once-weekly&#xD;
      administration of semaglutide in healthy Chinese subjects. Different dose levels (0.5 and 1.0&#xD;
      mg) will be investigated in this trial. Participants will be administered semaglutide or&#xD;
      placebo once-weekly by subcutaneous injection (under the skin fold of the abdominal wall)&#xD;
      using a pen injector with a very small, thin needle by the trial doctor at the trial site for&#xD;
      13 weeks. The trial consists of 23 visits in total, including visit for screening and safety&#xD;
      tests, visit for dose administration and blood sample collection. The total time of&#xD;
      participation will be approximately 18-22 weeks depending on participant's individual visit&#xD;
      schedule.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 21, 2017</start_date>
  <completion_date type="Actual">August 7, 2018</completion_date>
  <primary_completion_date type="Actual">July 10, 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>Parallel Assignment</intervention_model>
    <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 semaglutide plasma concentration time curve at steady state (semaglutide 0.5 mg)</measure>
    <time_frame>0-168 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the semaglutide plasma concentration time curve at steady state (semaglutide 1.0 mg)</measure>
    <time_frame>0-168 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed semaglutide plasma concentration at steady state</measure>
    <time_frame>0-168 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed semaglutide plasma concentration at steady state</measure>
    <time_frame>0-168 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total apparent clearance of semaglutide at steady state</measure>
    <time_frame>0-168 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life of semaglutide at steady state</measure>
    <time_frame>0-840 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution of semaglutide at steady state</measure>
    <time_frame>0-840 hours after last administration of semaglutide</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough plasma semaglutide concentration</measure>
    <time_frame>Before dosing at day 29, 57, 78, 85 and 92</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-corrected accumulation ratio</measure>
    <time_frame>Based on the area under the semaglutide plasma concentration curve from 0-168 hours after the first dose and the area under the semaglutide plasma concentration curve 0-168 hours after the last dose</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the semaglutide plasma concentration time curve</measure>
    <time_frame>0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed semaglutide plasma concentration</measure>
    <time_frame>0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed semaglutide plasma concentration</measure>
    <time_frame>0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)</time_frame>
    <description>Calculated based on semaglutide measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment emergent adverse events (TEAEs)</measure>
    <time_frame>Visit 2 (Day 1) - visit 23 (Day 120-127)</time_frame>
    <description>Count and % of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hypoglycaemic episodes</measure>
    <time_frame>Visit 2 (Day 1) - visit 23 (Day 120-127)</time_frame>
    <description>Count of episodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of anti-semaglutide antibodies (positive/negative) at follow-up</measure>
    <time_frame>Visit 23 (Day 120-127)</time_frame>
    <description>Count of episodes</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Diabetes</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Semaglutide 0.5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will enter a 13 weeks treatment with 4 weeks dosing at dose level 0.25 mg and 9 weeks at 0.5 mg semaglutide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Semaglutide 0.5 mg placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will enter a 13 weeks treatment with 4 weeks dosing at dose level 0.25 mg and 9 weeks at 0.5 mg semaglutide placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Semaglutide 1.0 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will have 13 weeks treatment with 4 weeks dosing at dose level of 0.25 mg, 4 weeks at 0.5 mg, and 5 weeks at 1.0 mg semaglutide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Semaglutide 1.0 mg placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will have 13 weeks treatment with 4 weeks dosing at dose level of 0.25 mg, 4 weeks at 0.5 mg, and 5 weeks at 1.0 mg semaglutide placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Semaglutide 0.5 mg</intervention_name>
    <description>A dose of 0.25 mg semaglutide gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.</description>
    <arm_group_label>Semaglutide 0.5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (semaglutide 0.5 mg)</intervention_name>
    <description>A dose of 0.25 mg semaglutide placebo gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.</description>
    <arm_group_label>Semaglutide 0.5 mg placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Semaglutide 1.0 mg</intervention_name>
    <description>A dose of 0.25 mg semaglutide gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.</description>
    <arm_group_label>Semaglutide 1.0 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (semaglutide 1.0 mg)</intervention_name>
    <description>A dose of 0.25 mg semaglutide placebo gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.</description>
    <arm_group_label>Semaglutide 1.0 mg placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female Chinese subjects&#xD;
&#xD;
          -  Age between 18 to 55 years (both inclusive) at the time of signing informed consent&#xD;
&#xD;
          -  Body mass index (BMI) between 20 and 24.9 kg/sqm (both inclusive)&#xD;
&#xD;
          -  Body weight greater than or equal to 54.0 kg&#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 method throughout the&#xD;
             trial including follow-up period. Adequate contraceptive measures are sterilisation,&#xD;
             intrauterine device (IUD), oral contraceptives or barrier methods&#xD;
&#xD;
          -  Any clinically significant disease history, in the opinion of the investigator, or&#xD;
             systemic or organ disease including: pulmonary, gastrointestinal, hepatic, neurologic,&#xD;
             renal, genitourinary and endocrine, dermatologic or hematologic diseases&#xD;
&#xD;
          -  Use of prescription or non-prescription systemic products (including routine or&#xD;
             non-routine vitamins or herbal products) or topical medicinal products (except&#xD;
             paracetamol and oral contraceptives) within 3 weeks (or within 5 half-lives of the&#xD;
             medicinal product, whichever is longest) prior to Visit 2 (randomisation)&#xD;
&#xD;
          -  Personal or family history of medullary thyroid carcinoma or multiple endocrine&#xD;
             neoplasia syndrome type 2&#xD;
&#xD;
          -  History of pancreatitis (acute or chronic)&#xD;
&#xD;
          -  Calcitonin greater than or equal to 50 ng/L&#xD;
&#xD;
          -  Blood donation, surgery or trauma with significant blood loss (400 mL) within the last&#xD;
             12 weeks prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Shi A, Xie P, Nielsen LL, Skjoth TV, He X, Haugaard SP. Pharmacokinetics, Safety and Tolerability of Once-Weekly Subcutaneous Semaglutide in Healthy Chinese Subjects: A Double-Blind, Phase 1, Randomized Controlled Trial. Adv Ther. 2021 Jan;38(1):550-561. doi: 10.1007/s12325-020-01548-y. Epub 2020 Nov 7.</citation>
    <PMID>33159658</PMID>
  </results_reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2021</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>
  <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/NCT03288740
org study id: NN9535-3686
secondary id: U1111-1149-6572
nct id: NCT03288740
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 assess the pharmacokinetics of semaglutide (i.e. the way
      the drug is distributed in the body over a period of time) following once-weekly
      administration of semaglutide in healthy Chinese subjects. Different dose levels (0.5 and 1.0
      mg) will be investigated in this trial. Participants will be administered semaglutide or
      placebo once-weekly by subcutaneous injection (under the skin fold of the abdominal wall)
      using a pen injector with a very small, thin needle by the trial doctor at the trial site for
      13 weeks. The trial consists of 23 visits in total, including visit for screening and safety
      tests, visit for dose administration and blood sample collection. The total time of
      participation will be approximately 18-22 weeks depending on participant's individual visit
      schedule.
allocation: Randomized
intervention model: Parallel Assignment
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 semaglutide plasma concentration time curve at steady state (semaglutide 0.5 mg)
time frame: 0-168 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Area under the semaglutide plasma concentration time curve at steady state (semaglutide 1.0 mg)
time frame: 0-168 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Maximum observed semaglutide plasma concentration at steady state
time frame: 0-168 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Time to maximum observed semaglutide plasma concentration at steady state
time frame: 0-168 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Total apparent clearance of semaglutide at steady state
time frame: 0-168 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Terminal elimination half-life of semaglutide at steady state
time frame: 0-840 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Apparent volume of distribution of semaglutide at steady state
time frame: 0-840 hours after last administration of semaglutide
description: Calculated based on semaglutide measured in blood.
measure: Trough plasma semaglutide concentration
time frame: Before dosing at day 29, 57, 78, 85 and 92
description: Calculated based on semaglutide measured in blood.
measure: Dose-corrected accumulation ratio
time frame: Based on the area under the semaglutide plasma concentration curve from 0-168 hours after the first dose and the area under the semaglutide plasma concentration curve 0-168 hours after the last dose
description: Calculated based on semaglutide measured in blood.
measure: Area under the semaglutide plasma concentration time curve
time frame: 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)
description: Calculated based on semaglutide measured in blood.
measure: Maximum observed semaglutide plasma concentration
time frame: 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)
description: Calculated based on semaglutide measured in blood.
measure: Time to maximum observed semaglutide plasma concentration
time frame: 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)
description: Calculated based on semaglutide measured in blood.
measure: Number of treatment emergent adverse events (TEAEs)
time frame: Visit 2 (Day 1) - visit 23 (Day 120-127)
description: Count and % of adverse events
measure: Number of hypoglycaemic episodes
time frame: Visit 2 (Day 1) - visit 23 (Day 120-127)
description: Count of episodes
measure: Incidence of anti-semaglutide antibodies (positive/negative) at follow-up
time frame: Visit 23 (Day 120-127)
description: Count of episodes
arm group label: Semaglutide 0.5 mg
arm group type: Experimental
description: Participants will enter a 13 weeks treatment with 4 weeks dosing at dose level 0.25 mg and 9 weeks at 0.5 mg semaglutide.
arm group label: Semaglutide 0.5 mg placebo
arm group type: Placebo Comparator
description: Participants will enter a 13 weeks treatment with 4 weeks dosing at dose level 0.25 mg and 9 weeks at 0.5 mg semaglutide placebo.
arm group label: Semaglutide 1.0 mg
arm group type: Experimental
description: Participants will have 13 weeks treatment with 4 weeks dosing at dose level of 0.25 mg, 4 weeks at 0.5 mg, and 5 weeks at 1.0 mg semaglutide.
arm group label: Semaglutide 1.0 mg placebo
arm group type: Placebo Comparator
description: Participants will have 13 weeks treatment with 4 weeks dosing at dose level of 0.25 mg, 4 weeks at 0.5 mg, and 5 weeks at 1.0 mg semaglutide placebo.
intervention type: Drug
intervention name: Semaglutide 0.5 mg
description: A dose of 0.25 mg semaglutide gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
arm group label: Semaglutide 0.5 mg
intervention type: Drug
intervention name: Placebo (semaglutide 0.5 mg)
description: A dose of 0.25 mg semaglutide placebo gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
arm group label: Semaglutide 0.5 mg placebo
intervention type: Drug
intervention name: Semaglutide 1.0 mg
description: A dose of 0.25 mg semaglutide gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
arm group label: Semaglutide 1.0 mg
intervention type: Drug
intervention name: Placebo (semaglutide 1.0 mg)
description: A dose of 0.25 mg semaglutide placebo gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
arm group label: Semaglutide 1.0 mg placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
citation: Shi A, Xie P, Nielsen LL, Skjoth TV, He X, Haugaard SP. Pharmacokinetics, Safety and Tolerability of Once-Weekly Subcutaneous Semaglutide in Healthy Chinese Subjects: A Double-Blind, Phase 1, Randomized Controlled Trial. Adv Ther. 2021 Jan;38(1):550-561. doi: 10.1007/s12325-020-01548-y. Epub 2020 Nov 7.
PMID: 33159658
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: Yes
ipd description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com