<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/NCT02249910</url>
  </required_header>
  <id_info>
    <org_study_id>NN9924-4145</org_study_id>
    <secondary_id>2013-004820-12</secondary_id>
    <secondary_id>U1111-1150-0801</secondary_id>
    <nct_id>NCT02249910</nct_id>
  </id_info>
  <brief_title>Investigating the Influence of Oral Semaglutide on Pharmacokinetics of Metformin and Digoxin in Healthy Subjects</brief_title>
  <official_title>An Open-label, Single Arm, Sequential, Single Centre Trial Investigating the Influence of Oral Semaglutide on Pharmacokinetics of Metformin and Digoxin in Healthy 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is conducted in Europe. The aim of this trial is to investigate the influence of&#xD;
      oral semaglutide on pharmacokinetics (the exposure of the trial drug in the body) of&#xD;
      metformin and digoxin in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2014</start_date>
  <completion_date type="Actual">March 6, 2015</completion_date>
  <primary_completion_date type="Actual">March 6, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the metformin plasma concentration-time curve</measure>
    <time_frame>During a dosing interval (0 to12 hours) at steady state</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the digoxin plasma concentration-time curve</measure>
    <time_frame>From time 0 to infinity after single dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed metformin plasma concentration</measure>
    <time_frame>During a dosing interval (0 to 12 hours) at steady state</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed digoxin plasma concentration</measure>
    <time_frame>0 to 120 hours after single dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed semaglutide plasma concentration</measure>
    <time_frame>During a dosing interval (0 to 24 hours) at steady state</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the SNAC plasma concentration-time curve</measure>
    <time_frame>During a dosing interval (0 to 24 hours) at steady state</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hypoglycaemic episodes</measure>
    <time_frame>From the first dosing (Day 1) and until completion of the post treatment follow up visit (Day 118-122)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Diabetes</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Semaglutide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>semaglutide</intervention_name>
    <description>Oral administration of 5 mg daily for one week, then escalated to 10 mg daily for one week, followed by escalation to 20 mg daily for 41 days</description>
    <arm_group_label>Semaglutide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin</intervention_name>
    <description>Oral administration of 850 mg twice daily for 3 days followed by 850 mg on day 4, assessed in 3 dosing periods 1) alone, 2) co-administration with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) and 3) co-administration with oral semaglutide.</description>
    <arm_group_label>Semaglutide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>digoxin</intervention_name>
    <description>Oral administration of 0.5 mg single dose, assessed in 3 dosing periods 1) alone, 2) co-administration with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) and 3) co-administration with oral semaglutide.</description>
    <arm_group_label>Semaglutide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Oral administration of SNAC 300 mg. Will be administered with the morning dose of metformin (1st, 3rd, 5th and 7th dose). On Day 24, a single SNAC dose will be administered with digoxin.</description>
    <arm_group_label>Semaglutide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, age 18-75 years (both inclusive) at the time of signing inform consent&#xD;
&#xD;
          -  Body mass index (BMI) 20.0-29.9 kg/m^2 (both inclusive)&#xD;
&#xD;
          -  A good general health based on medical history, physical examination, and results of&#xD;
             vital signs, electrocardiogram and laboratory safety tests performed during the&#xD;
             screening visit, as judged by the investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female who is pregnant, breast-feeding or intends to become pregnant or is of&#xD;
             child-bearing potential and not using adequate contraceptive methods. Female of child&#xD;
             bearing potential must use effective methods of birth control for the duration of the&#xD;
             trial and for 5 weeks following last dose. Only highly effective methods of birth&#xD;
             control are accepted (i.e., one that results in a less than 1% per year failure rate&#xD;
             when used consistently and correctly, such as implants, injectables, combined oral&#xD;
             contraceptives, and some intrauterine devices)&#xD;
&#xD;
          -  History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease&#xD;
&#xD;
          -  Hypertension (defined as sitting systolic blood pressure above 140 mmHg and/or&#xD;
             diastolic blood pressure above 90 mmHg). If white-coat hypertension is suspected at&#xD;
             the screening visit a repeated measurement is allowed&#xD;
&#xD;
          -  Any blood draw in excess of 25 mL in the past month, or donation of blood or plasma in&#xD;
             excess of 400 mL within the 3 months preceding screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Registry (GCR, 1452)</last_name>
    <role>Study Director</role>
    <affiliation>Novo Nordisk A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>14050</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://novonordisk-trials.com</url>
    <description>Clinical Trials at Novo Nordisk</description>
  </link>
  <reference>
    <citation>Baekdal TA, Borregaard J, Hansen CW, Thomsen M, Anderson TW. Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects. Clin Pharmacokinet. 2019 Sep;58(9):1193-1203. doi: 10.1007/s40262-019-00756-2.</citation>
    <PMID>30945118</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>February 13, 2020</last_update_submitted>
  <last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Digoxin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02249910
org study id: NN9924-4145
secondary id: 2013-004820-12
secondary id: U1111-1150-0801
nct id: NCT02249910
lead sponsor: 
has dmc: No
This trial is conducted in Europe. The aim of this trial is to investigate the influence of
      oral semaglutide on pharmacokinetics (the exposure of the trial drug in the body) of
      metformin and digoxin in healthy subjects.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the metformin plasma concentration-time curve
time frame: During a dosing interval (0 to12 hours) at steady state
measure: Area under the digoxin plasma concentration-time curve
time frame: From time 0 to infinity after single dose
measure: Maximum observed metformin plasma concentration
time frame: During a dosing interval (0 to 12 hours) at steady state
measure: Maximum observed digoxin plasma concentration
time frame: 0 to 120 hours after single dose
measure: Maximum observed semaglutide plasma concentration
time frame: During a dosing interval (0 to 24 hours) at steady state
measure: Area under the SNAC plasma concentration-time curve
time frame: During a dosing interval (0 to 24 hours) at steady state
measure: Number of hypoglycaemic episodes
time frame: From the first dosing (Day 1) and until completion of the post treatment follow up visit (Day 118-122)
arm group label: Semaglutide
arm group type: Experimental
intervention type: Drug
intervention name: semaglutide
description: Oral administration of 5 mg daily for one week, then escalated to 10 mg daily for one week, followed by escalation to 20 mg daily for 41 days
arm group label: Semaglutide
intervention type: Drug
intervention name: metformin
description: Oral administration of 850 mg twice daily for 3 days followed by 850 mg on day 4, assessed in 3 dosing periods 1) alone, 2) co-administration with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) and 3) co-administration with oral semaglutide.
arm group label: Semaglutide
intervention type: Drug
intervention name: digoxin
description: Oral administration of 0.5 mg single dose, assessed in 3 dosing periods 1) alone, 2) co-administration with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) and 3) co-administration with oral semaglutide.
arm group label: Semaglutide
intervention type: Drug
intervention name: placebo
description: Oral administration of SNAC 300 mg. Will be administered with the morning dose of metformin (1st, 3rd, 5th and 7th dose). On Day 24, a single SNAC dose will be administered with digoxin.
arm group label: Semaglutide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Global Clinical Registry (GCR, 1452)
role: Study Director
affiliation: Novo Nordisk A/S
facility: 
country: Germany
url: http://novonordisk-trials.com
description: Clinical Trials at Novo Nordisk
citation: Baekdal TA, Borregaard J, Hansen CW, Thomsen M, Anderson TW. Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects. Clin Pharmacokinet. 2019 Sep;58(9):1193-1203. doi: 10.1007/s40262-019-00756-2.
PMID: 30945118
responsible party type: Sponsor
mesh term: Metformin
mesh term: Digoxin