<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/NCT01664624</url>
  </required_header>
  <id_info>
    <org_study_id>ROF-T2D_107</org_study_id>
    <secondary_id>U1111-1128-6945</secondary_id>
    <nct_id>NCT01664624</nct_id>
  </id_info>
  <brief_title>Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes</brief_title>
  <official_title>A Phase 1b, Randomized, Double-Blind, Active Comparator (Open-Label Exenatide) Controlled Study to Evaluate the Effect of Roflumilast Plus Alogliptin on Postprandial Active GLP-1 Level and 24-hour Glucose Level in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on a Stable Dose of Metformin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effect of roflumilast plus alogliptin on&#xD;
      glucagon-like peptide-1 (GLP-1) and glucose levels in patients with type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study to evaluate the antiglycemic efficacy and safety of roflumilast + alogliptin&#xD;
      compared to alogliptin alone and roflumilast alone; it will also include an open-label&#xD;
      exenatide treatment arm as a control. The antiglycemic efficacy of the combination will be&#xD;
      evaluated through the measurement of postprandial active GLP-1 level, ß cell secretion&#xD;
      activity (via the measurement of C-peptide and insulin levels), appetite sensations (as&#xD;
      assessed by VAS) and glycemic control as assessed by a continuous glucose monitoring system&#xD;
      (CGMS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">November 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</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>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1</measure>
    <time_frame>Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
    <description>The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in AUC(0-8) of Postprandial Plasma Glucose</measure>
    <time_frame>Baseline and Day 11 at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
    <description>The concentration of glucose in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and baseline postprandial AUC (0-8) of plasma glucose as a continuous covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Postprandial AUC(0-8) of C-peptide</measure>
    <time_frame>Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
    <description>The concentration of C-peptide in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of C-peptide as a continuous covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Postprandial AUC(0-8) of Insulin</measure>
    <time_frame>Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
    <description>The concentration of insulin in blood before and up to 8 hours after eating was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of insulin as a continuous covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Day 11 in AUC(0-8) of Appetite Sensation</measure>
    <time_frame>At Baseline and Day 11, every 30 minutes, starting 1 hour before eating until 8 hour after the meal.</time_frame>
    <description>Appetite sensations were measured using a visual analog scale (VAS) questionnaire. Participants were asked to indicate their level of fullness, hunger, satiety, and prospective consumption (how much do you think you can eat?) on a 100 mm line ranging from &quot;Not at all&quot; (0 mm) to &quot;extremely&quot; (100 mm). Appetite sensation scores before and up to 8 hours after eating were plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of appetite sensation VAS score as a continuous covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Day 11 in 24-hour Average Plasma Glucose</measure>
    <time_frame>Baseline (Day -1) and Day 11, from 12 AM through 24 hours.</time_frame>
    <description>Plasma glucose was measured by Continuous Glucose Monitoring System (CGMS). CGMS measures glucose every 5 minutes, starting in the fasting state 8 hour prior to the standardized breakfast (12 AM) until 16 hours after the breakfast. The average 24-hour plasma glucose concentration was calculated. Least squares means were obtained using an ANCOVA model with treatment as fixed effect, and Baseline 24-hour Glucose Measured by CGMS as a continuous covariate.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Roflumilast + alogliptin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alogliptin alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Roflumilast alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exenatide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Roflumilast</intervention_name>
    <description>Roflumilast tablets</description>
    <arm_group_label>Roflumilast + alogliptin</arm_group_label>
    <arm_group_label>Roflumilast alone</arm_group_label>
    <other_name>Daxas, Daliresp</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alogliptin</intervention_name>
    <description>Alogliptin tablets</description>
    <arm_group_label>Alogliptin alone</arm_group_label>
    <arm_group_label>Roflumilast + alogliptin</arm_group_label>
    <other_name>Nesina</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide</intervention_name>
    <description>Exenatide solution</description>
    <arm_group_label>Exenatide</arm_group_label>
    <other_name>Byetta</other_name>
    <other_name>Bydureon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to roflumilast</intervention_name>
    <description>Placebo-matching roflumilast tablets</description>
    <arm_group_label>Alogliptin alone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to alogliptin</intervention_name>
    <description>Placebo-matching alogliptin tablets</description>
    <arm_group_label>Roflumilast alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, aged 18 to 80 years, inclusive, at the time of dosing on Day 1.&#xD;
&#xD;
          2. Has an historical diagnosis of type 2 diabetes mellitus (T2DM) disease.&#xD;
&#xD;
          3. Has a documented history of a diet and exercise plan and is receiving metformin as&#xD;
             monotherapy at a stable dose for at least 8 weeks prior to Screening; has no chronic&#xD;
             use (&gt;7 days) of any other antidiabetic therapy within the 8 weeks prior to Screening.&#xD;
&#xD;
          4. Has inadequate glycemic control at Screening, as evidenced by HbA1c (glycosylated&#xD;
             hemoglobin) level between 7.0% and 10.0%, inclusive.&#xD;
&#xD;
          5. Has a body mass index (BMI) of ≥23.0 kg/m^2 and ≤45.0 kg/m^2, at Screening.&#xD;
&#xD;
          6. A female of childbearing potential who is sexually active with a nonsterilized male&#xD;
             partner agrees to use routinely adequate contraception from signing of informed&#xD;
             consent throughout the duration of the study and for 30 days after the last dose of&#xD;
             study drug.&#xD;
&#xD;
          7. A male who is nonsterilized and sexually active with a female partner of childbearing&#xD;
             potential agrees to use adequate contraception from signing of informed consent&#xD;
             throughout the duration of the study and for 30 days after last dose of study drug&#xD;
&#xD;
          8. In the opinion of the investigator, the participant is capable of understanding and&#xD;
             complying with protocol requirements.&#xD;
&#xD;
          9. The participant or, when applicable, the participant's legally acceptable&#xD;
             representative signs and dates a written, informed consent form and any required&#xD;
             privacy authorization prior to the initiation of any study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has a history of type 1 diabetes.&#xD;
&#xD;
          2. Has a history of acute metabolic diabetic complications.&#xD;
&#xD;
          3. Has has abnormal Screening or Check-in (Day -2) laboratory values that suggest a&#xD;
             clinically significant underlying disease (eg, active liver disease or jaundice) or&#xD;
             participant with the following laboratory abnormalities: alanine aminotransferase&#xD;
             (ALT) and/or aspartate aminotransferase (AST) &gt;3 × upper limit of normal (ULN).&#xD;
&#xD;
          4. Has a history of diabetic gastroparesis or history of gastric bypass surgery.&#xD;
&#xD;
          5. Has a history of coronary angioplasty, coronary stent placement, coronary bypass&#xD;
             surgery, or myocardial infarction within 6 months prior to Screening.&#xD;
&#xD;
          6. Has New York Heart Association heart failure of Class (III-IV) regardless of therapy.&#xD;
&#xD;
          7. Has a supine blood pressure &gt;150 mm Hg for systolic or &gt;90 mm Hg for diastolic,&#xD;
             confirmed on repeat testing within a maximum of 5 minutes, at Screening and Check-in&#xD;
             (Day -2).&#xD;
&#xD;
          8. Has presence or history of neuropsychiatric disorder (eg, psychosis, psychotic&#xD;
             disorders, depression associated with suicidal thinking, suicidal ideation or&#xD;
             behavior).&#xD;
&#xD;
          9. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol&#xD;
             abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per&#xD;
             day) within the past 2 years or is unwilling to agree to abstain from alcohol and&#xD;
             drugs throughout the study.&#xD;
&#xD;
         10. Has a hemoglobin ≤120 g/L for men and ≤100 g/L for women.&#xD;
&#xD;
         11. Has a history of clinically significant allergies or idiosyncrasies to roflumilast,&#xD;
             alogliptin and exenatide or any inactive ingredient(s) of these products, eg, rare&#xD;
             hereditary problems of galactose intolerance, the Lapp lactase deficiency,&#xD;
             glucose-galactose malabsorption or phenylketonuria.&#xD;
&#xD;
         12. Has received alogliptin or roflumilast in a previous clinical study or as a&#xD;
             therapeutic agent within 2 months prior to Screening, or is taking prescription&#xD;
             roflumilast for chronic obstructive pulmonary disease (COPD), or has received any&#xD;
             other investigational compound within 30 days prior to the first dose of study&#xD;
             medication, or is participating or plans to participate in any other clinical trial&#xD;
             during this study.&#xD;
&#xD;
         13. If female, is pregnant or lactating or intending to become pregnant before, during, or&#xD;
             within 30 days after last dose; or intending to donate ova during such time period.&#xD;
&#xD;
         14. If male, intends to donate sperm during the course of the study or for 30 days after&#xD;
             last dose of study medication.&#xD;
&#xD;
         15. Is an immediate family member, study site employee, or in a dependent relationship&#xD;
             with a study site employee who is involved in the conduct of this study (eg, spouse,&#xD;
             parent, child, sibling) or may consent under duress.&#xD;
&#xD;
         16. Has a history of cancer, except basal cell or squamous cell carcinoma which has been&#xD;
             in remission for at least 5 years prior to Day 1.&#xD;
&#xD;
         17. Serum creatinine ≥1.5 mg/dL for males and ≥1.4 mg/dL for females or creatinine&#xD;
             clearance &lt;60 mL/minutes, based on calculation by central lab using the&#xD;
             Cockcroft-Gault approximation at Screening Visit.&#xD;
&#xD;
         18. Has a history of any hemoglobinopathy that may affect determination of HbA1c.&#xD;
&#xD;
         19. Has positive test result for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody&#xD;
             (HCV), any known history of infection with human immunodeficiency virus (HIV), any&#xD;
             acute infection, or severe immunological diseases (eg, multiple sclerosis, systemic&#xD;
             lupus erythematosus, and progressive multifocal leukoencephalopathy).&#xD;
&#xD;
         20. Has a risk of suicide according to the Investigator's clinical judgment per&#xD;
             Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide&#xD;
             attempt in the past 6 months.&#xD;
&#xD;
         21. Has any clinically relevant abnormal laboratory values suggesting an unknown disease&#xD;
             and requiring further clinical evaluation (as assessed by the investigator).&#xD;
&#xD;
         22. Does not have an adequate standard of literacy to allow him or her to complete the&#xD;
             study diary during non-clinic days.&#xD;
&#xD;
         23. Has poor peripheral venous access.&#xD;
&#xD;
         24. Has Screening or Check-in (Day -2) abnormal clinically significant electrocardiogram&#xD;
             (ECG). Entry of any participant with abnormal not clinically significant ECG must be&#xD;
             approved and documented by signature of Principal Investigator and Medical Monitor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>AstraZeneca AstraZeneca</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <results_first_submitted>November 25, 2013</results_first_submitted>
  <results_first_submitted_qc>January 22, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 20, 2014</results_first_posted>
  <last_update_submitted>December 2, 2016</last_update_submitted>
  <last_update_submitted_qc>December 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Therapy</keyword>
  <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>Exenatide</mesh_term>
    <mesh_term>Alogliptin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 2 investigative sites in the United States from 10 July 2012 to 29 November 2012.</recruitment_details>
      <pre_assignment_details>Participants with a diagnosis of type 2 diabetes mellitus and inadequate glycemic control were enrolled equally in 1 of 4 treatment groups, roflumilast + alogliptin, alogliptin alone, roflumilast alone, or exenatide.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Roflumilast + Alogliptin</title>
          <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
        </group>
        <group group_id="P2">
          <title>Alogliptin Alone</title>
          <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
        </group>
        <group group_id="P3">
          <title>Roflumilast Alone</title>
          <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
        </group>
        <group group_id="P4">
          <title>Exenatide</title>
          <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Roflumilast + Alogliptin</title>
          <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
        </group>
        <group group_id="B2">
          <title>Alogliptin Alone</title>
          <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
        </group>
        <group group_id="B3">
          <title>Roflumilast Alone</title>
          <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
        </group>
        <group group_id="B4">
          <title>Exenatide</title>
          <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
        </group>
        <group group_id="B5">
          <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="10"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="9"/>
            <count group_id="B5" value="40"/>
          </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="50.7" spread="10.15"/>
                    <measurement group_id="B2" value="52.9" spread="7.52"/>
                    <measurement group_id="B3" value="60.7" spread="4.24"/>
                    <measurement group_id="B4" value="54.6" spread="6.88"/>
                    <measurement group_id="B5" value="54.7" spread="8.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="171.1" spread="8.91"/>
                    <measurement group_id="B2" value="171.2" spread="6.03"/>
                    <measurement group_id="B3" value="166.6" spread="10.44"/>
                    <measurement group_id="B4" value="166.4" spread="5.90"/>
                    <measurement group_id="B5" value="169.0" spread="8.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="103.12" spread="21.688"/>
                    <measurement group_id="B2" value="93.24" spread="11.670"/>
                    <measurement group_id="B3" value="89.33" spread="17.961"/>
                    <measurement group_id="B4" value="86.98" spread="14.713"/>
                    <measurement group_id="B5" value="93.32" spread="17.329"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.93" spread="4.708"/>
                    <measurement group_id="B2" value="31.75" spread="3.184"/>
                    <measurement group_id="B3" value="32.03" spread="5.311"/>
                    <measurement group_id="B4" value="31.37" spread="4.653"/>
                    <measurement group_id="B5" value="32.53" spread="4.548"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking Classification</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Never smoked</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Current smoker</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ex-smoker</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of Diabetes</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.9" spread="4.63"/>
                    <measurement group_id="B2" value="8.5" spread="6.39"/>
                    <measurement group_id="B3" value="7.0" spread="3.86"/>
                    <measurement group_id="B4" value="8.2" spread="6.63"/>
                    <measurement group_id="B5" value="7.7" spread="5.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Metformin Dose</title>
          <units>mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="875.0" spread="151.38"/>
                    <measurement group_id="B2" value="745.0" spread="225.40"/>
                    <measurement group_id="B3" value="805.0" spread="220.42"/>
                    <measurement group_id="B4" value="855.6" spread="211.31"/>
                    <measurement group_id="B5" value="819.2" spread="202.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1</title>
        <description>The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.</description>
        <time_frame>Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
        <population>Full analysis set defined as all randomized participants included in the safety analysis. Only participants with data at both Baseline and post-baseline visits are included.</population>
        <group_list>
          <group group_id="O1">
            <title>Roflumilast + Alogliptin</title>
            <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O2">
            <title>Alogliptin Alone</title>
            <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O3">
            <title>Roflumilast Alone</title>
            <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
          </group>
          <group group_id="O4">
            <title>Exenatide</title>
            <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1</title>
          <description>The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.</description>
          <population>Full analysis set defined as all randomized participants included in the safety analysis. Only participants with data at both Baseline and post-baseline visits are included.</population>
          <units>pmol/L*hr</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="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.5" spread="4.04"/>
                    <measurement group_id="O2" value="31.6" spread="4.01"/>
                    <measurement group_id="O3" value="3.8" spread="3.94"/>
                    <measurement group_id="O4" value="-2.3" spread="4.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>ANCOVA was used to test the null hypothesis that the change from Baseline in the postprandial AUC(0-8) of active GLP-1 is no difference between the roflumilast + alogliptin and alogliptin alone.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.388</p_value>
            <p_value_desc>The comparison was evaluated at the 5% level of significance.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>ANCOVA model with treatment as fixed effect, and baseline Postprandial AUC (0-8) of active GLP-1 as a continuous covariate.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>-5.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.82</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.9</ci_lower_limit>
            <ci_upper_limit>6.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>ANCOVA was used to test the null hypothesis that the change from Baseline in the postprandial AUC(0-8) of active GLP-1 is no difference between the roflumilast + alogliptin and roflumilast alone.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>The comparison was evaluated at the 5% level of significance.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>ANCOVA model with treatment as fixed effect, and Baseline Postprandial AUC (0-8) of active GLP-1 as a continuous covariate.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>22.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.70</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>11.1</ci_lower_limit>
            <ci_upper_limit>34.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>ANCOVA was used to test the null hypothesis that the change from Baseline in the postprandial AUC(0-8) of active GLP-1 is no difference between the roflumilast + alogliptin and roflumilast alone.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>The comparison was evaluated at the 5% level of significance.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>ANCOVA model with treatment as fixed effect, and Baseline Postprandial AUC (0-8) of active GLP-1 as a continuous covariate.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>28.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.76</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>17.1</ci_lower_limit>
            <ci_upper_limit>40.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in AUC(0-8) of Postprandial Plasma Glucose</title>
        <description>The concentration of glucose in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and baseline postprandial AUC (0-8) of plasma glucose as a continuous covariate.</description>
        <time_frame>Baseline and Day 11 at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
        <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
        <group_list>
          <group group_id="O1">
            <title>Roflumilast + Alogliptin</title>
            <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O2">
            <title>Alogliptin Alone</title>
            <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O3">
            <title>Roflumilast Alone</title>
            <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
          </group>
          <group group_id="O4">
            <title>Exenatide</title>
            <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in AUC(0-8) of Postprandial Plasma Glucose</title>
          <description>The concentration of glucose in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and baseline postprandial AUC (0-8) of plasma glucose as a continuous covariate.</description>
          <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
          <units>mmol/L*hr</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="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.4" spread="2.70"/>
                    <measurement group_id="O2" value="-9.8" spread="2.71"/>
                    <measurement group_id="O3" value="-9.0" spread="2.71"/>
                    <measurement group_id="O4" value="-18.5" spread="2.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Postprandial AUC(0-8) of C-peptide</title>
        <description>The concentration of C-peptide in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of C-peptide as a continuous covariate.</description>
        <time_frame>Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
        <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
        <group_list>
          <group group_id="O1">
            <title>Roflumilast + Alogliptin</title>
            <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O2">
            <title>Alogliptin Alone</title>
            <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O3">
            <title>Roflumilast Alone</title>
            <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
          </group>
          <group group_id="O4">
            <title>Exenatide</title>
            <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Postprandial AUC(0-8) of C-peptide</title>
          <description>The concentration of C-peptide in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of C-peptide as a continuous covariate.</description>
          <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
          <units>ng/mL*hr</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="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="1.15"/>
                    <measurement group_id="O2" value="1.4" spread="1.16"/>
                    <measurement group_id="O3" value="-0.7" spread="1.17"/>
                    <measurement group_id="O4" value="0.0" spread="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Postprandial AUC(0-8) of Insulin</title>
        <description>The concentration of insulin in blood before and up to 8 hours after eating was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of insulin as a continuous covariate.</description>
        <time_frame>Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).</time_frame>
        <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
        <group_list>
          <group group_id="O1">
            <title>Roflumilast + Alogliptin</title>
            <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O2">
            <title>Alogliptin Alone</title>
            <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O3">
            <title>Roflumilast Alone</title>
            <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
          </group>
          <group group_id="O4">
            <title>Exenatide</title>
            <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Postprandial AUC(0-8) of Insulin</title>
          <description>The concentration of insulin in blood before and up to 8 hours after eating was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of insulin as a continuous covariate.</description>
          <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
          <units>pmol/L*hr</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="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-49.5" spread="181.09"/>
                    <measurement group_id="O2" value="107.8" spread="180.75"/>
                    <measurement group_id="O3" value="26.9" spread="180.38"/>
                    <measurement group_id="O4" value="-136.4" spread="190.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Day 11 in AUC(0-8) of Appetite Sensation</title>
        <description>Appetite sensations were measured using a visual analog scale (VAS) questionnaire. Participants were asked to indicate their level of fullness, hunger, satiety, and prospective consumption (how much do you think you can eat?) on a 100 mm line ranging from &quot;Not at all&quot; (0 mm) to &quot;extremely&quot; (100 mm). Appetite sensation scores before and up to 8 hours after eating were plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of appetite sensation VAS score as a continuous covariate.</description>
        <time_frame>At Baseline and Day 11, every 30 minutes, starting 1 hour before eating until 8 hour after the meal.</time_frame>
        <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
        <group_list>
          <group group_id="O1">
            <title>Roflumilast + Alogliptin</title>
            <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O2">
            <title>Alogliptin Alone</title>
            <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O3">
            <title>Roflumilast Alone</title>
            <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
          </group>
          <group group_id="O4">
            <title>Exenatide</title>
            <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Day 11 in AUC(0-8) of Appetite Sensation</title>
          <description>Appetite sensations were measured using a visual analog scale (VAS) questionnaire. Participants were asked to indicate their level of fullness, hunger, satiety, and prospective consumption (how much do you think you can eat?) on a 100 mm line ranging from &quot;Not at all&quot; (0 mm) to &quot;extremely&quot; (100 mm). Appetite sensation scores before and up to 8 hours after eating were plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of appetite sensation VAS score as a continuous covariate.</description>
          <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
          <units>mm*hr</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="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Fullness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.5" spread="59.73"/>
                    <measurement group_id="O2" value="62.0" spread="56.52"/>
                    <measurement group_id="O3" value="136.0" spread="57.81"/>
                    <measurement group_id="O4" value="116.8" spread="59.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-103.6" spread="52.61"/>
                    <measurement group_id="O2" value="3.1" spread="52.18"/>
                    <measurement group_id="O3" value="-132.7" spread="52.44"/>
                    <measurement group_id="O4" value="-122.5" spread="54.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prospective consumption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-97.1" spread="54.24"/>
                    <measurement group_id="O2" value="-14.9" spread="53.76"/>
                    <measurement group_id="O3" value="-169.5" spread="53.98"/>
                    <measurement group_id="O4" value="-124.3" spread="56.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Satiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-82.7" spread="53.66"/>
                    <measurement group_id="O2" value="-3.2" spread="52.96"/>
                    <measurement group_id="O3" value="-139.2" spread="53.58"/>
                    <measurement group_id="O4" value="-127.7" spread="55.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Day 11 in 24-hour Average Plasma Glucose</title>
        <description>Plasma glucose was measured by Continuous Glucose Monitoring System (CGMS). CGMS measures glucose every 5 minutes, starting in the fasting state 8 hour prior to the standardized breakfast (12 AM) until 16 hours after the breakfast. The average 24-hour plasma glucose concentration was calculated. Least squares means were obtained using an ANCOVA model with treatment as fixed effect, and Baseline 24-hour Glucose Measured by CGMS as a continuous covariate.</description>
        <time_frame>Baseline (Day -1) and Day 11, from 12 AM through 24 hours.</time_frame>
        <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
        <group_list>
          <group group_id="O1">
            <title>Roflumilast + Alogliptin</title>
            <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O2">
            <title>Alogliptin Alone</title>
            <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
          </group>
          <group group_id="O3">
            <title>Roflumilast Alone</title>
            <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
          </group>
          <group group_id="O4">
            <title>Exenatide</title>
            <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Day 11 in 24-hour Average Plasma Glucose</title>
          <description>Plasma glucose was measured by Continuous Glucose Monitoring System (CGMS). CGMS measures glucose every 5 minutes, starting in the fasting state 8 hour prior to the standardized breakfast (12 AM) until 16 hours after the breakfast. The average 24-hour plasma glucose concentration was calculated. Least squares means were obtained using an ANCOVA model with treatment as fixed effect, and Baseline 24-hour Glucose Measured by CGMS as a continuous covariate.</description>
          <population>Full analysis set. Only participants with data at both Baseline and post-baseline visits are included.</population>
          <units>mg/dL</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="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-25.4" spread="6.67"/>
                    <measurement group_id="O2" value="-17.5" spread="6.67"/>
                    <measurement group_id="O3" value="-14.5" spread="6.66"/>
                    <measurement group_id="O4" value="-34.9" spread="7.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study medication to no more than 30 days after the last dose of the study medication (a maximum of 41 days).</time_frame>
      <desc>At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Roflumilast + Alogliptin</title>
          <description>Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.</description>
        </group>
        <group group_id="E2">
          <title>Alogliptin Alone</title>
          <description>Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.</description>
        </group>
        <group group_id="E3">
          <title>Roflumilast Alone</title>
          <description>Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.</description>
        </group>
        <group group_id="E4">
          <title>Exenatide</title>
          <description>Exenatide 5 μg subcutaneous injection twice a day for 11 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.1)</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="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.1)</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="6" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lip injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="9"/>
              </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>Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights therefrom or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>AstraZeneca Clinical Study Information Center</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.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/NCT01664624
org study id: ROF-T2D_107
secondary id: U1111-1128-6945
nct id: NCT01664624
lead sponsor: 
has dmc: No
The purpose of this study is to assess the effect of roflumilast plus alogliptin on
      glucagon-like peptide-1 (GLP-1) and glucose levels in patients with type 2 diabetes.
This is a study to evaluate the antiglycemic efficacy and safety of roflumilast + alogliptin
      compared to alogliptin alone and roflumilast alone; it will also include an open-label
      exenatide treatment arm as a control. The antiglycemic efficacy of the combination will be
      evaluated through the measurement of postprandial active GLP-1 level, ß cell secretion
      activity (via the measurement of C-peptide and insulin levels), appetite sensations (as
      assessed by VAS) and glycemic control as assessed by a continuous glucose monitoring system
      (CGMS).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1
time frame: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).
description: The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.
measure: Change From Baseline in AUC(0-8) of Postprandial Plasma Glucose
time frame: Baseline and Day 11 at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).
description: The concentration of glucose in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and baseline postprandial AUC (0-8) of plasma glucose as a continuous covariate.
measure: Change From Baseline in Postprandial AUC(0-8) of C-peptide
time frame: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).
description: The concentration of C-peptide in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of C-peptide as a continuous covariate.
measure: Change From Baseline in Postprandial AUC(0-8) of Insulin
time frame: Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).
description: The concentration of insulin in blood before and up to 8 hours after eating was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of insulin as a continuous covariate.
measure: Change From Baseline to Day 11 in AUC(0-8) of Appetite Sensation
time frame: At Baseline and Day 11, every 30 minutes, starting 1 hour before eating until 8 hour after the meal.
description: Appetite sensations were measured using a visual analog scale (VAS) questionnaire. Participants were asked to indicate their level of fullness, hunger, satiety, and prospective consumption (how much do you think you can eat?) on a 100 mm line ranging from "Not at all" (0 mm) to "extremely" (100 mm). Appetite sensation scores before and up to 8 hours after eating were plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an ANCOVA model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of appetite sensation VAS score as a continuous covariate.
measure: Change From Baseline to Day 11 in 24-hour Average Plasma Glucose
time frame: Baseline (Day -1) and Day 11, from 12 AM through 24 hours.
description: Plasma glucose was measured by Continuous Glucose Monitoring System (CGMS). CGMS measures glucose every 5 minutes, starting in the fasting state 8 hour prior to the standardized breakfast (12 AM) until 16 hours after the breakfast. The average 24-hour plasma glucose concentration was calculated. Least squares means were obtained using an ANCOVA model with treatment as fixed effect, and Baseline 24-hour Glucose Measured by CGMS as a continuous covariate.
arm group label: Roflumilast + alogliptin
arm group type: Experimental
description: Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.
arm group label: Alogliptin alone
arm group type: Experimental
description: Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.
arm group label: Roflumilast alone
arm group type: Experimental
description: Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.
arm group label: Exenatide
arm group type: Active Comparator
description: Exenatide 5 μg subcutaneous injection twice a day for 11 days.
intervention type: Drug
intervention name: Roflumilast
description: Roflumilast tablets
arm group label: Roflumilast + alogliptin
arm group label: Roflumilast alone
other name: Daxas, Daliresp
intervention type: Drug
intervention name: Alogliptin
description: Alogliptin tablets
arm group label: Alogliptin alone
arm group label: Roflumilast + alogliptin
other name: Nesina
intervention type: Drug
intervention name: Exenatide
description: Exenatide solution
arm group label: Exenatide
other name: Byetta
other name: Bydureon
intervention type: Drug
intervention name: Placebo to roflumilast
description: Placebo-matching roflumilast tablets
arm group label: Alogliptin alone
intervention type: Drug
intervention name: Placebo to alogliptin
description: Placebo-matching alogliptin tablets
arm group label: Roflumilast alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: AstraZeneca AstraZeneca
role: Study Director
affiliation: AstraZeneca
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Exenatide
mesh term: Alogliptin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 