<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/NCT02205528</url>
  </required_header>
  <id_info>
    <org_study_id>NN9709-4336</org_study_id>
    <secondary_id>U1111-1189-5627</secondary_id>
    <nct_id>NCT02205528</nct_id>
  </id_info>
  <brief_title>A Study of Once-Daily NNC0090-2746 in Participants With Type 2 Diabetes Inadequately Controlled With Metformin</brief_title>
  <official_title>A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Phase 2a Study With an Open-Label Active Group to Assess the Efficacy and Safety of Once-Daily NNC0090-2746 in Type 2 Diabetic Patients Inadequately Controlled With Metformin</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>
  <brief_summary>
    <textblock>
      This trial is conducted in the United States of America (USA). The aim of the trial is to&#xD;
      investigate the efficacy, safety, and tolerability of once-daily subcutaneous (SC) injections&#xD;
      of NNC0090-2746 for 12 weeks, as an adjunct to metformin, in participants with T2D.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2014</start_date>
  <completion_date type="Actual">September 15, 2015</completion_date>
  <primary_completion_date type="Actual">September 15, 2015</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>Day 1; Week 8</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in body weight</measure>
    <time_frame>Day 1; Week 8; Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in body weight</measure>
    <time_frame>Day 1; Week 8; Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting plasma glucose (FPG)</measure>
    <time_frame>Day 1; Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in post-prandial plasma glucose level</measure>
    <time_frame>Day -7; Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in post-prandial insulin level</measure>
    <time_frame>Day -7; Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in post-prandial C-peptide level</measure>
    <time_frame>Day -7; Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in beta-cell function</measure>
    <time_frame>Day 1; Week 12</time_frame>
    <description>According to the Homeostasis Model Assessment (HOMA) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events</measure>
    <time_frame>Day 1; Week 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in percent HbA1c</measure>
    <time_frame>Day 1; Week 12</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">108</enrollment>
  <condition>Diabetes</condition>
  <condition>Diabetes Mellitus Type 2</condition>
  <arm_group>
    <arm_group_label>Treatment Period: Placebo QD</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive daily SC placebo injections during the 12-week, double-blind treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Period: NNC0090-2746 QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive daily 1.8-mg SC injections of NNC0090-2746 during the 12-week, double-blind treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Period: Liraglutide QD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive open-label liraglutide via SC injection during the 12-week treatment period. The dose scheme will be as follows: 0.6 milligrams (mg) each day during Week 1, followed by 1.2 mg each day during Week 2, and 1.8 mg each day from Weeks 3 to 12.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liraglutide</intervention_name>
    <description>Liraglutide will be self-administered daily via SC injection according to manufacturer specifications.</description>
    <arm_group_label>Treatment Period: Liraglutide QD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin hydrochloride immediate- or extended-release oral tablets will be supplied by the participant or investigational site as standard-of-care treatment beginning at least 8 weeks prior to randomization and throughout the 12-week treatment period. Metformin will also be continued during the 4-week follow-up. Dose selection will be based upon manufacturer specifications.</description>
    <arm_group_label>Treatment Period: Liraglutide QD</arm_group_label>
    <arm_group_label>Treatment Period: NNC0090-2746 QD</arm_group_label>
    <arm_group_label>Treatment Period: Placebo QD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo to NNC0090-2746 will be self-administered daily via SC injection.</description>
    <arm_group_label>Treatment Period: Placebo QD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NNC0090-2746</intervention_name>
    <description>NNC0090-2746 solution will be self-administered in daily doses of 1.8 mg via SC injection.</description>
    <arm_group_label>Treatment Period: NNC0090-2746 QD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants aged 18 to 70 years, inclusive&#xD;
&#xD;
          -  Active diagnosis of T2D for greater than or equal to (&gt;/=) 3 months&#xD;
&#xD;
          -  For females of childbearing potential and males with female partners of childbearing&#xD;
             potential, agreement to use highly effective contraceptive measures&#xD;
&#xD;
          -  Treated with a stable dose of metformin for at least 8 weeks prior to randomization,&#xD;
             and expected to remain at the same stable dose throughout study participation&#xD;
&#xD;
          -  Hemoglobin A1c (HbA1c) &gt;/= 7.2% and less than or equal to (&lt;/=) 10.5%&#xD;
&#xD;
          -  Fasting plasma glucose (FPG) less than (&lt;) 250 milligrams per deciliter (mg/dL)&#xD;
&#xD;
          -  C-peptide greater than (&gt;) 1.5 nanograms per milliliter (ng/mL)&#xD;
&#xD;
          -  Body mass index (BMI) &gt;/= 27 kilograms per meter-squared (kg/m^2) and &lt;/= 44 kg/m^2&#xD;
&#xD;
          -  Stable weight (+/- 5%) within 12 weeks prior to Screening&#xD;
&#xD;
          -  Willing and able to maintain existing diet and exercise habits throughout the study&#xD;
&#xD;
          -  Capable of performing SC self-injections on a daily basis during the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females who are pregnant or lactating&#xD;
&#xD;
          -  History of type 1 diabetes (T1D), diabetes resulting from pancreatic injury, or&#xD;
             secondary forms of diabetes such as Cushing's Syndrome or acromegaly&#xD;
&#xD;
          -  History of acute metabolic complications such as diabetic ketoacidosis or state of&#xD;
             hyperosmolar hyperglycemia&#xD;
&#xD;
          -  History of clinically significant diabetic complications such as diabetic&#xD;
             proliferative retinopathy or severe diabetic neuropathy (requiring treatment with&#xD;
             antidepressants or opioids)&#xD;
&#xD;
          -  History of severe hypoglycemia within 6 months prior to Screening&#xD;
&#xD;
          -  History of chronic gastrointestinal (GI) conditions that could impede gastric emptying&#xD;
             or potentially affect the interpretation of the study data&#xD;
&#xD;
          -  History of weight loss surgery or weight loss procedure involving the GI tract, such&#xD;
             as gastric bypass, gastric stapling, or gastric banding&#xD;
&#xD;
          -  History of an eating disorder (e.g., bulimia, anorexia)&#xD;
&#xD;
          -  History of malignancy (except treated basal or squamous cell skin cancer) within 5&#xD;
             years prior to Screening&#xD;
&#xD;
          -  Personal or family history of medullary thyroid carcinoma&#xD;
&#xD;
          -  History of multiple endocrine neoplasia syndrome type 2&#xD;
&#xD;
          -  History of chronic or acute pancreatitis or hemochromatosis&#xD;
&#xD;
          -  History of significant cardiovascular disease (such as congestive heart failure New&#xD;
             York Heart Association Class II to IV, myocardial infarction within the previous 6&#xD;
             months, coronary disease, or uncontrolled hypertension)&#xD;
&#xD;
          -  History of clinically significant renal or liver disease&#xD;
&#xD;
          -  History of hypersensitivity or previous intolerance to incretin or glucagon analogues&#xD;
&#xD;
          -  Elevations in lipase or amylase levels at Screening &gt; 1.5 times the upper limit of&#xD;
             normal (ULN) and considered clinically significant by the investigator&#xD;
&#xD;
          -  Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAG), or&#xD;
             hepatitis C antibody test at Screening&#xD;
&#xD;
          -  Receipt of an investigational drug within 30 days or 5 half-lives, whichever is&#xD;
             longer, prior to Screening, or active enrollment in another investigational medication&#xD;
             or device study&#xD;
&#xD;
          -  Any condition, disorder, or abnormal laboratory test findings at screening that, in&#xD;
             the judgment of the investigator, would interfere with the participant's ability to&#xD;
             comply with all study requirements, or would require the administration of a treatment&#xD;
             during the study that could potentially affect the interpretation of the study data,&#xD;
             or would place the participant at unacceptable risk by his/her participation in the&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</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>Chino</city>
        <state>California</state>
        <zip>91710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hawaiian Gardens</city>
        <state>California</state>
        <zip>90716</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90057</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>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sanford</city>
        <state>Florida</state>
        <zip>32771</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Oxon Hill</city>
        <state>Maryland</state>
        <zip>20745</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Corpus Christi</city>
        <state>Texas</state>
        <zip>78404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Manassas</city>
        <state>Virginia</state>
        <zip>20110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Frias JP, Bastyr EJ 3rd, Vignati L, Tschop MH, Schmitt C, Owen K, Christensen RH, DiMarchi RD. The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes. Cell Metab. 2017 Aug 1;26(2):343-352.e2. doi: 10.1016/j.cmet.2017.07.011.</citation>
    <PMID>28768173</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <disposition_first_submitted>September 3, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>September 3, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 5, 2018</disposition_first_posted>
  <last_update_submitted>July 20, 2020</last_update_submitted>
  <last_update_submitted_qc>July 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2020</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>Metformin</mesh_term>
    <mesh_term>Liraglutide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02205528
org study id: NN9709-4336
secondary id: U1111-1189-5627
nct id: NCT02205528
lead sponsor: 
This trial is conducted in the United States of America (USA). The aim of the trial is to
      investigate the efficacy, safety, and tolerability of once-daily subcutaneous (SC) injections
      of NNC0090-2746 for 12 weeks, as an adjunct to metformin, in participants with T2D.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in HbA1c
time frame: Day 1; Week 8
measure: Change in body weight
time frame: Day 1; Week 8; Week 12
measure: Percent change in body weight
time frame: Day 1; Week 8; Week 12
measure: Change in fasting plasma glucose (FPG)
time frame: Day 1; Week 12
measure: Change in post-prandial plasma glucose level
time frame: Day -7; Week 12
measure: Change in post-prandial insulin level
time frame: Day -7; Week 12
measure: Change in post-prandial C-peptide level
time frame: Day -7; Week 12
measure: Change in beta-cell function
time frame: Day 1; Week 12
description: According to the Homeostasis Model Assessment (HOMA) score
measure: Incidence of treatment-emergent adverse events
time frame: Day 1; Week 18
measure: Change in percent HbA1c
time frame: Day 1; Week 12
arm group label: Treatment Period: Placebo QD
arm group type: Placebo Comparator
description: Participants will receive daily SC placebo injections during the 12-week, double-blind treatment period.
arm group label: Treatment Period: NNC0090-2746 QD
arm group type: Experimental
description: Participants will receive daily 1.8-mg SC injections of NNC0090-2746 during the 12-week, double-blind treatment period.
arm group label: Treatment Period: Liraglutide QD
arm group type: Active Comparator
description: Participants will receive open-label liraglutide via SC injection during the 12-week treatment period. The dose scheme will be as follows: 0.6 milligrams (mg) each day during Week 1, followed by 1.2 mg each day during Week 2, and 1.8 mg each day from Weeks 3 to 12.
intervention type: Drug
intervention name: Liraglutide
description: Liraglutide will be self-administered daily via SC injection according to manufacturer specifications.
arm group label: Treatment Period: Liraglutide QD
intervention type: Drug
intervention name: Metformin
description: Metformin hydrochloride immediate- or extended-release oral tablets will be supplied by the participant or investigational site as standard-of-care treatment beginning at least 8 weeks prior to randomization and throughout the 12-week treatment period. Metformin will also be continued during the 4-week follow-up. Dose selection will be based upon manufacturer specifications.
arm group label: Treatment Period: Liraglutide QD
arm group label: Treatment Period: NNC0090-2746 QD
arm group label: Treatment Period: Placebo QD
intervention type: Drug
intervention name: Placebo
description: Matching placebo to NNC0090-2746 will be self-administered daily via SC injection.
arm group label: Treatment Period: Placebo QD
intervention type: Drug
intervention name: NNC0090-2746
description: NNC0090-2746 solution will be self-administered in daily doses of 1.8 mg via SC injection.
arm group label: Treatment Period: NNC0090-2746 QD
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Registry (GCR,1452)
role: Study Director
affiliation: Novo Nordisk A/S
facility: 
facility: 
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facility: 
facility: 
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country: United States
citation: Frias JP, Bastyr EJ 3rd, Vignati L, Tschop MH, Schmitt C, Owen K, Christensen RH, DiMarchi RD. The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes. Cell Metab. 2017 Aug 1;26(2):343-352.e2. doi: 10.1016/j.cmet.2017.07.011.
PMID: 28768173
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Metformin
mesh term: Liraglutide