<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/NCT01677299</url>
  </required_header>
  <id_info>
    <org_study_id>LCPOC10</org_study_id>
    <nct_id>NCT01677299</nct_id>
  </id_info>
  <brief_title>Assessing the PK and Effect on Glucose and GI Hormone Concentrations of Metformin Delayed-Release in Subjects With T2DM</brief_title>
  <official_title>A Randomized, Crossover Study Assessing the Effects of pH 6.5 Enteric Coating of Metformin HCl Tablets on Pharmacokinetics and Changes in Circulating Glucose and Gastrointestinal Hormone Concentrations in Subjects With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Elcelyx Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Elcelyx Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate how EFB0027 and EFB0026 behave in subjects with type 2 diabetes&#xD;
      mellitus.&#xD;
&#xD;
      In addition, this study will compare the effects of EFB0027 and EFB0026 on circulating&#xD;
      concentrations of glucose and gastrointestinal hormones in subjects with type 2 diabetes&#xD;
      mellitus.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve (0-t) of Plasma Metformin</measure>
    <time_frame>Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.</time_frame>
    <description>Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Fasting Plasma Glucose</measure>
    <time_frame>Change from Baseline (Day 1) to Day 5</time_frame>
    <description>LS mean difference from Baseline (Day 1) to Day 5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Within Treatment Comparison Based on Ratios of AUCs of GLP-1</measure>
    <time_frame>Ratio of Day 5 to Baseline</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Within Treatment Comparison Based on Ratios of AUCs of PYY</measure>
    <time_frame>Ratio of Day 5 to Baseline</time_frame>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>1000 mg EFB0026 (metformin immediate-release)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1000 mg EFB0027 (metformin delayed-release)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>500 mg EFB0027 (metformin delayed-release)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>500 mg EFB0026 + 1000 mg EFB0027</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EFB0027 (metformin delayed release)</intervention_name>
    <description>Comparison of enteric-coating to assess effect on PK</description>
    <arm_group_label>1000 mg EFB0027 (metformin delayed-release)</arm_group_label>
    <arm_group_label>500 mg EFB0026 + 1000 mg EFB0027</arm_group_label>
    <arm_group_label>500 mg EFB0027 (metformin delayed-release)</arm_group_label>
    <other_name>Met DR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EFB0026 (metformin immediate-release)</intervention_name>
    <description>Active comparator</description>
    <arm_group_label>1000 mg EFB0026 (metformin immediate-release)</arm_group_label>
    <arm_group_label>500 mg EFB0026 + 1000 mg EFB0027</arm_group_label>
    <other_name>Met IR</other_name>
    <other_name>metformin</other_name>
    <other_name>Glucophage</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Is 19 to 70 (inclusive) years old at Visit 1 (Screening).&#xD;
&#xD;
          2. Is diagnosed with Type 2 Diabetes Mellitus with&#xD;
&#xD;
               -  HbA1c between 6.0 to 9.5% (inclusive) for subjects managing their diabetes with:&#xD;
&#xD;
                  i. Diet and exercise alone, or ii. A stable regimen (minimum of 2 months at Visit&#xD;
                  1) of metformin alone, or iii. A stable regimen (minimum of 2 months at Visit 1)&#xD;
                  of DPP-4 inhibitor alone, OR&#xD;
&#xD;
               -  HbA1c between 6.0 to 8.5% (inclusive) for subjects managing their diabetes with a&#xD;
                  stable (minimum of 2 months at Visit 1) combination regimen of metformin and&#xD;
                  DPP-4 inhibitors.&#xD;
&#xD;
          3. Has serum creatinine below the upper limit of normal at Visit 1 and an estimated&#xD;
             creatinine clearance above 80 using the Crockroft and Gault equation (CrCl = [(140 -&#xD;
             age) x body weight in kg] / (serum creatinine x 72) x (0.85 for females) [ref. 3].&#xD;
&#xD;
          4. Has a body mass index (BMI) of 25.0 to 40.0 kg/m^2 (inclusive) at Screening.&#xD;
&#xD;
          5. Is male, or is female and meets all of the following criteria:&#xD;
&#xD;
               -  Not breastfeeding&#xD;
&#xD;
               -  Negative pregnancy test result (human chorionic gonadotropin, beta subunit) at&#xD;
                  Visit 1 (Screening) (not applicable to hysterectomized females)&#xD;
&#xD;
               -  Surgically sterile, postmenopausal, or if of childbearing potential, must&#xD;
                  practice and be willing to continue to practice appropriate birth control during&#xD;
                  the entire duration of the study&#xD;
&#xD;
          6. Has a physical examination with no clinically significant abnormalities as judged by&#xD;
             the investigator.&#xD;
&#xD;
          7. Ability to understand and willingness to adhere to protocol requirements.&#xD;
&#xD;
          8. If on chronic thyroid pharmacologic therapy, the dose must be stable for at least 3&#xD;
             months prior to Visit 1 (Screening), and must have thyroid-stimulating hormone (TSH)&#xD;
             test result in normal range at Visit 1 (Screening).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has a clinically significant medical condition that could potentially affect study&#xD;
             participation and/or personal well-being, as judged by the investigator, including but&#xD;
             not limited to the following conditions:&#xD;
&#xD;
               -  Hepatic disease&#xD;
&#xD;
               -  Renal disease&#xD;
&#xD;
               -  Gastrointestinal disease&#xD;
&#xD;
               -  Endocrine disorder except diabetes&#xD;
&#xD;
               -  Cardiovascular disease&#xD;
&#xD;
               -  Seizure disorder&#xD;
&#xD;
               -  Organ transplantation&#xD;
&#xD;
               -  Chronic infection&#xD;
&#xD;
          2. Has any chronic disease requiring medication that has been adjusted in the past 90&#xD;
             days (subjects may take acute intermittent over-the-counter medications such as&#xD;
             Tylenol, if needed).&#xD;
&#xD;
          3. Has any drug treatment that affects gastric pH (prescription or over-the-counter),&#xD;
             including any antacids or medications such as Rolaids or Pepcid within 2 days of Visit&#xD;
             1 (Screening).&#xD;
&#xD;
          4. Has had major surgery of any kind within 6 months of Visit 1 (Screening).&#xD;
&#xD;
          5. Has received a blood transfusion within 6 months of Visit 1 (Screening).&#xD;
&#xD;
          6. Has a history of &gt;5 kg weight change within 3 months of Visit 1 (Screening).&#xD;
&#xD;
          7. Has clinical laboratory test (clinical chemistry, hematology, or urinalysis)&#xD;
             abnormalities other than those expected in subjects with diabetes and judged by the&#xD;
             investigator to be clinically significant at Visit 1 (Screening).&#xD;
&#xD;
          8. Has physical, psychological, or historical finding that, in the investigator's&#xD;
             opinion, would make the subject unsuitable for the study.&#xD;
&#xD;
          9. Currently abuses drugs or alcohol or has a history of abuse that in the investigator's&#xD;
             opinion would cause the individual to be noncompliant with study procedures.&#xD;
&#xD;
         10. Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate&#xD;
             blood during the study.&#xD;
&#xD;
         11. Has used insulin within 3 months of Visit 1 (Screening).&#xD;
&#xD;
         12. Has received GLP-1 receptor agonists and/or thiazolidinedione treatment within 6&#xD;
             months of Visit 1 (Screening).&#xD;
&#xD;
         13. Has known intolerance to metformin.&#xD;
&#xD;
         14. Has received any investigational drug within 1 month (or five half-lives of the&#xD;
             investigational drug, whichever is greater) of Visit 1 (Screening).&#xD;
&#xD;
         15. Has known allergies or hypersensitivity to any component of study treatment.&#xD;
&#xD;
         16. Is employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract&#xD;
             worker, or designee of the company).&#xD;
&#xD;
         17. Smokes more than 10 cigarettes per day, 2 cigars per day, or uses more than 1 can of&#xD;
             smokeless tobacco per week.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Celerion, Inc.</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Celerion, Inc.</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016 Aug;59(8):1645-54. doi: 10.1007/s00125-016-3992-6. Epub 2016 May 23.</citation>
    <PMID>27216492</PMID>
  </reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <results_first_submitted>February 12, 2014</results_first_submitted>
  <results_first_submitted_qc>May 15, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 16, 2014</results_first_posted>
  <last_update_submitted>August 12, 2016</last_update_submitted>
  <last_update_submitted_qc>August 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 20, 2016</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>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sequence 1: BCAD</title>
          <description>BID&#xD;
Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)</description>
        </group>
        <group group_id="P2">
          <title>Sequence 2: ABDC</title>
          <description>BID&#xD;
Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)</description>
        </group>
        <group group_id="P3">
          <title>Sequence 3: CDBA</title>
          <description>BID&#xD;
Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)</description>
        </group>
        <group group_id="P4">
          <title>Sequence 4: DACB</title>
          <description>BID&#xD;
Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </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="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sequence BCAD</title>
          <description>A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID</description>
        </group>
        <group group_id="B2">
          <title>Sequence ABDC</title>
          <description>A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID</description>
        </group>
        <group group_id="B3">
          <title>Sequence CDBA</title>
          <description>A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID</description>
        </group>
        <group group_id="B4">
          <title>Sequence DACB</title>
          <description>A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID</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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="24"/>
          </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="43.2" spread="3.54"/>
                    <measurement group_id="B2" value="56.8" spread="7.22"/>
                    <measurement group_id="B3" value="49.7" spread="13.92"/>
                    <measurement group_id="B4" value="55.3" spread="7.79"/>
                    <measurement group_id="B5" value="51.3" spread="9.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</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="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <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="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/mˆ2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.13" spread="5.455"/>
                    <measurement group_id="B2" value="30.67" spread="2.793"/>
                    <measurement group_id="B3" value="35.65" spread="2.935"/>
                    <measurement group_id="B4" value="32.87" spread="3.644"/>
                    <measurement group_id="B5" value="33.33" spread="4.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>eGFR</title>
          <units>mL/min/1.73 mˆ2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="117.94" spread="22.065"/>
                    <measurement group_id="B2" value="114.65" spread="21.348"/>
                    <measurement group_id="B3" value="107.54" spread="16.644"/>
                    <measurement group_id="B4" value="93.43" spread="20.354"/>
                    <measurement group_id="B5" value="108.39" spread="21.161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HbA1c</title>
          <units>%</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.62" spread="1.234"/>
                    <measurement group_id="B2" value="7.33" spread="0.965"/>
                    <measurement group_id="B3" value="8.07" spread="1.102"/>
                    <measurement group_id="B4" value="6.37" spread=".339"/>
                    <measurement group_id="B5" value="7.35" spread="1.108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>FPG</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="182.5" spread="71.55"/>
                    <measurement group_id="B2" value="158" spread="42.96"/>
                    <measurement group_id="B3" value="179" spread="69.59"/>
                    <measurement group_id="B4" value="124.3" spread="15.03"/>
                    <measurement group_id="B5" value="161" spread="56.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve (0-t) of Plasma Metformin</title>
        <description>Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.</description>
        <time_frame>Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.</time_frame>
        <population>Evaluable Population</population>
        <group_list>
          <group group_id="O1">
            <title>1000 mg EFB0026</title>
            <description>BID</description>
          </group>
          <group group_id="O2">
            <title>1000 mg EFB0027</title>
            <description>BID</description>
          </group>
          <group group_id="O3">
            <title>500 mg EFB0027</title>
            <description>BID</description>
          </group>
          <group group_id="O4">
            <title>500 mg EFB0026 + 1000 mg EFB0027</title>
            <description>BID</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve (0-t) of Plasma Metformin</title>
          <description>Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.</description>
          <population>Evaluable Population</population>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8672" spread="29.7"/>
                    <measurement group_id="O2" value="4774" spread="29.9"/>
                    <measurement group_id="O3" value="3842" spread="37.6"/>
                    <measurement group_id="O4" value="8075" spread="38.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Fasting Plasma Glucose</title>
        <description>LS mean difference from Baseline (Day 1) to Day 5</description>
        <time_frame>Change from Baseline (Day 1) to Day 5</time_frame>
        <population>Evaluable Population</population>
        <group_list>
          <group group_id="O1">
            <title>1000 mg EFB0026</title>
            <description>BID&#xD;
EFB0026: Active comparator</description>
          </group>
          <group group_id="O2">
            <title>1000 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK</description>
          </group>
          <group group_id="O3">
            <title>500 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK</description>
          </group>
          <group group_id="O4">
            <title>500 mg EFB0026 + 1000 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK&#xD;
EFB0026: Active comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fasting Plasma Glucose</title>
          <description>LS mean difference from Baseline (Day 1) to Day 5</description>
          <population>Evaluable Population</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="19"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.5" spread="6.8"/>
                    <measurement group_id="O2" value="-19.9" spread="5"/>
                    <measurement group_id="O3" value="-16.4" spread="3.8"/>
                    <measurement group_id="O4" value="-21.2" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Change in fasting plasma glucose from Baseline to Day 5 (end of treatment) for treatment A.</method_desc>
            <param_type>LS mean diff (Day 5 - Baseline)</param_type>
            <param_value>-22.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-37</ci_lower_limit>
            <ci_upper_limit>-8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Change in fasting plasma glucose from Baseline to Day 5 (end of treatment) for treatment B.</method_desc>
            <param_type>LS mean diff (Day 5 - Baseline)</param_type>
            <param_value>-20</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-30</ci_lower_limit>
            <ci_upper_limit>-9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Change in fasting plasma glucose from Baseline to Day 5 (end of treatment) for treatment C.</method_desc>
            <param_type>LS mean diff (Day 5 - Baseline)</param_type>
            <param_value>-16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-24</ci_lower_limit>
            <ci_upper_limit>-8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Change in fasting plasma glucose from Baseline to Day 5 (end of treatment) for treatment D.</method_desc>
            <param_type>LS mean diff (Day 5 - Baseline)</param_type>
            <param_value>-21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-31</ci_lower_limit>
            <ci_upper_limit>-11</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Within Treatment Comparison Based on Ratios of AUCs of GLP-1</title>
        <time_frame>Ratio of Day 5 to Baseline</time_frame>
        <population>Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>1000 mg EFB0026</title>
            <description>BID&#xD;
EFB0026: Active comparator</description>
          </group>
          <group group_id="O2">
            <title>1000 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK</description>
          </group>
          <group group_id="O3">
            <title>500 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK</description>
          </group>
          <group group_id="O4">
            <title>500 mg EFB0026 + 1000 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK&#xD;
EFB0026: Active comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Within Treatment Comparison Based on Ratios of AUCs of GLP-1</title>
          <population>Evaluable</population>
          <units>none (values are ratios)</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="19"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.87" spread="0.18"/>
                    <measurement group_id="O2" value="1.62" spread=".11"/>
                    <measurement group_id="O3" value="1.69" spread=".15"/>
                    <measurement group_id="O4" value="1.88" spread=".19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geometric LS mean ration</param_type>
            <param_value>1.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.4</ci_lower_limit>
            <ci_upper_limit>1.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio of (Day 5/Baseline)</param_type>
            <param_value>1.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.5</ci_lower_limit>
            <ci_upper_limit>2.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio (Day 5/Baseline)</param_type>
            <param_value>1.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.4</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio (Day 5/Baseline)</param_type>
            <param_value>1.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.5</ci_lower_limit>
            <ci_upper_limit>2.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Within Treatment Comparison Based on Ratios of AUCs of PYY</title>
        <time_frame>Ratio of Day 5 to Baseline</time_frame>
        <population>Evaluable Population</population>
        <group_list>
          <group group_id="O1">
            <title>1000 mg EFB0026</title>
            <description>BID&#xD;
EFB0026: Active comparator</description>
          </group>
          <group group_id="O2">
            <title>1000 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK</description>
          </group>
          <group group_id="O3">
            <title>500 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK</description>
          </group>
          <group group_id="O4">
            <title>500 mg EFB0026 + 1000 mg EFB0027</title>
            <description>BID&#xD;
EFB0027: Comparison of enteric-coating to assess effect on PK&#xD;
EFB0026: Active comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Within Treatment Comparison Based on Ratios of AUCs of PYY</title>
          <population>Evaluable Population</population>
          <units>none (values are ratios)</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="19"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.55" spread=".09"/>
                    <measurement group_id="O2" value="1.38" spread=".09"/>
                    <measurement group_id="O3" value="1.46" spread=".06"/>
                    <measurement group_id="O4" value="1.49" spread=".06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio (Day 5/Baseline)</param_type>
            <param_value>1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.4</ci_lower_limit>
            <ci_upper_limit>1.8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio (Day 5/Baseline)</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.2</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio (Day 5/Baseline)</param_type>
            <param_value>1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.3</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Geo LSmean ratio (Day 5/Baseline)</param_type>
            <param_value>1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.4</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Population Intent to treat (ITT)</desc>
      <group_list>
        <group group_id="E1">
          <title>1000 mg EFB0026 BID</title>
          <description>A: Metformin immediate release BID</description>
        </group>
        <group group_id="E2">
          <title>1000 mg EFB0027 BID</title>
          <description>B: Metformin delayed release BID</description>
        </group>
        <group group_id="E3">
          <title>500 mg EFB0027 BID</title>
          <description>C: Metformin delayed release BID</description>
        </group>
        <group group_id="E4">
          <title>500 mg EFB0026 BID Plus 1000 mg EFB0027 BID</title>
          <description>D: Metformin immediate plus Metformin delayed release</description>
        </group>
      </group_list>
      <serious_events>
        <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="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Stromal Tumour</sub_title>
                <description>3 periods completed: C,D,B. During washout period, the subject experienced severe cramping and throbbing pain on his right side and was hospitalized. The investigator assessed this event as not related to study medication.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Frequent Bowel Movements</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Oral Herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Stromal Tumor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sinus Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
              </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>The results of the Study may be published by INSTITUTE, however the publication shall not disclose any SPONSOR Confidential Information, the INSTITUTE shall send the SPONSOR a copy of any such proposed publication 90 days prior to submission for publication, the INSTITUTE, on request of the SPONSOR, shall delete any SPONSOR Confidential Information in the proposed publication, and the INSTITUTE shall, on the SPONSOR's request, delay submission while the SPONSOR files applications for patents.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Director, Development</name_or_title>
      <organization>Elcelyx Therapeutics, Inc</organization>
      <phone>858-876-1814</phone>
      <email>info@elcelyx.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/NCT01677299
org study id: LCPOC10
nct id: NCT01677299
lead sponsor: 
has dmc: No
This study will evaluate how EFB0027 and EFB0026 behave in subjects with type 2 diabetes
      mellitus.

      In addition, this study will compare the effects of EFB0027 and EFB0026 on circulating
      concentrations of glucose and gastrointestinal hormones in subjects with type 2 diabetes
      mellitus.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Area Under the Curve (0-t) of Plasma Metformin
time frame: Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.
description: Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.
measure: Change in Fasting Plasma Glucose
time frame: Change from Baseline (Day 1) to Day 5
description: LS mean difference from Baseline (Day 1) to Day 5
measure: Within Treatment Comparison Based on Ratios of AUCs of GLP-1
time frame: Ratio of Day 5 to Baseline
measure: Within Treatment Comparison Based on Ratios of AUCs of PYY
time frame: Ratio of Day 5 to Baseline
arm group label: 1000 mg EFB0026 (metformin immediate-release)
arm group type: Active Comparator
description: BID
arm group label: 1000 mg EFB0027 (metformin delayed-release)
arm group type: Experimental
description: BID
arm group label: 500 mg EFB0027 (metformin delayed-release)
arm group type: Experimental
description: BID
arm group label: 500 mg EFB0026 + 1000 mg EFB0027
arm group type: Experimental
description: BID
intervention type: Drug
intervention name: EFB0027 (metformin delayed release)
description: Comparison of enteric-coating to assess effect on PK
arm group label: 1000 mg EFB0027 (metformin delayed-release)
arm group label: 500 mg EFB0026 + 1000 mg EFB0027
arm group label: 500 mg EFB0027 (metformin delayed-release)
other name: Met DR
intervention type: Drug
intervention name: EFB0026 (metformin immediate-release)
description: Active comparator
arm group label: 1000 mg EFB0026 (metformin immediate-release)
arm group label: 500 mg EFB0026 + 1000 mg EFB0027
other name: Met IR
other name: metformin
other name: Glucophage
criteria: 
gender: All
minimum age: 19 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
facility: 
country: United States
citation: DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016 Aug;59(8):1645-54. doi: 10.1007/s00125-016-3992-6. Epub 2016 May 23.
PMID: 27216492
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Metformin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 