<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/NCT02223065</url>
  </required_header>
  <id_info>
    <org_study_id>CV181-364</org_study_id>
    <nct_id>NCT02223065</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State</brief_title>
  <official_title>A Bioequivalence Study of Fixed-dose Combination Tablet of 5 Milligrams Saxagliptin/10 Milligrams Dapagliflozin Relative to Their Respective Individual Components Coadministered to Healthy Subjects in the Fasted State</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 demonstrate bioequivalence of coadministered drugs on healthy&#xD;
      subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Saxagliptin Maximum Observed Concentrations (Cmax)</measure>
    <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
    <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dapagliflozin Maximum Observed Concentrations (Cmax)</measure>
    <time_frame>Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)</time_frame>
    <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])</measure>
    <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
    <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])</measure>
    <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
    <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])</measure>
    <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
    <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])</measure>
    <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
    <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral dose of FDC (fixed-dose combination) tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saxagliptin</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <other_name>Onglyza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <other_name>Farxiga in the United States</other_name>
    <other_name>Forxiga in other countries</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form&#xD;
&#xD;
               -  Signed written informed consent must be obtained from the subjects in accordance&#xD;
                  with requirements of the study center's IRB or IEC before the initiation of any&#xD;
                  protocol-required procedures.&#xD;
&#xD;
          2. Target Population&#xD;
&#xD;
               -  Healthy subjects as determined by no clinically significant deviation from normal&#xD;
                  in medical history, psychiatric history, physical examination findings, vital&#xD;
                  sign measurements, 12-lead ECG measurements, physical measurements, and clinical&#xD;
                  laboratory test results.&#xD;
&#xD;
          3. Age and Reproductive Status&#xD;
&#xD;
               -  Males and females, ages 19 to 55 years, inclusive. To extent possible, the&#xD;
                  distribution of men and women between the sequences will be balanced&#xD;
&#xD;
               -  Women of childbearing potential (WOCBP) must have a negative serum or urine&#xD;
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24&#xD;
                  hours prior to the start of study drug.&#xD;
&#xD;
               -  Women must not be breastfeeding. d) WOCBP must agree to follow instructions for&#xD;
                  method(s) of contraception for the duration of treatment with study drugs&#xD;
                  saxagliptin and dapagliflozin plus 5 half lives of study drug dapagliflozin (the&#xD;
                  longer half life between the 2 drugs; 3 days) for a total of 3 days following&#xD;
                  treatment completion.&#xD;
&#xD;
                  e) Men who are sexually active with WOCBP must agree to follow instructions for&#xD;
                  method(s) of contraception for the duration of treatment with study drugs&#xD;
                  saxagliptin and dapagliflozin plus 5 half lives of dapagliflozin (the longer half&#xD;
                  life between the 2 drugs; 3 days) for a total of 3 days following treatment&#xD;
                  completion.&#xD;
&#xD;
                  f) Azoospermic males and WOCBP who are continuously not heterosexually active are&#xD;
                  exempt from contraceptive requirements. However, they must still undergo&#xD;
                  pregnancy testing as described in this section&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               -  Any significant acute or chronic medical illness.&#xD;
&#xD;
               -  Current or recent (within 3 months of study drug administration) gastrointestinal&#xD;
                  disease that could impact upon the absorption of study drug&#xD;
&#xD;
               -  Any other sound medical, psychiatric, and/or social reason as determined by the&#xD;
                  investigator&#xD;
&#xD;
               -  Any major surgery within 4 weeks of study drug administration.&#xD;
&#xD;
               -  Any prior GI surgery including cholecystectomy (remote history of appendectomy&#xD;
                  will not be exclusionary).&#xD;
&#xD;
               -  Current, recent (within 3 months of study drug administration), or remote history&#xD;
                  of pancreatitis.&#xD;
&#xD;
               -  Donation of blood or plasma to a blood bank or in a clinical study (except at&#xD;
                  screening visit) within 4 weeks before study drug administration.&#xD;
&#xD;
               -  Blood transfusion within 4 weeks of study drug administration. h) Inability to&#xD;
                  tolerate oral medication.&#xD;
&#xD;
               -  Inability to be venipunctured performed and/or tolerate venous access.&#xD;
&#xD;
               -  Use of tobacco- or nicotine-containing products (including, but not limited to,&#xD;
                  cigarettes, pipes, e-cigarettes, cigars, chewing tobacco, nicotine patches,&#xD;
                  nicotine lozenges, or nicotine gum) within 6 months before check-in.&#xD;
&#xD;
               -  Drug or alcohol abuse (within 2 years of study drug administration) as defined in&#xD;
                  the Diagnostic and Statistical Manual of Mental Disorders - 4th Edition,&#xD;
                  Diagnostic Criteria for Drug and Alcohol Abuse History of glucose intolerance or&#xD;
                  diabetes mellitus.&#xD;
&#xD;
               -  For females, history of chronic or recurrent urinary tract infection (UTI)&#xD;
                  (defined as 3 occurrences per year) or UTI in the past 3 months. For males, any&#xD;
                  UTI within the previous 5 years that has not been thoroughly evaluated and for&#xD;
                  which an explanation is not clear.&#xD;
&#xD;
               -  History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal&#xD;
                  mycotic infections.&#xD;
&#xD;
               -  Any other sound medical, psychiatric, and/or social reason as determined by the&#xD;
                  investigator.&#xD;
&#xD;
             Physical and Laboratory Test Findings&#xD;
&#xD;
               1. Evidence of organ dysfunction or any clinically significant deviation from normal&#xD;
                  in physical examination, vital signs, ECGs, or clinical laboratory determinations&#xD;
                  beyond what is consistent with the target population.&#xD;
&#xD;
               2. Abnormal urinalysis at screening (may repeat once). If the urinalysis is abnormal&#xD;
                  on Day -1 of Period 1, continuation in the study is up to the investigator's&#xD;
                  discretion. The CRO medical monitor should be consulted.&#xD;
&#xD;
               3. Glucosuria or hematoria at screening or Day -1 of Period 1, repeat is not&#xD;
                  permitted. d) A positive nicotine test (ie, cotinine).&#xD;
&#xD;
             e) Abnormal liver function tests (alanine or aspartate aminotransferase [ALT or AST,&#xD;
             respectively], or total bilirubin).&#xD;
&#xD;
             f) Any of the following on 12-lead ECG prior to study drug administration, confirmed&#xD;
             by repeat.&#xD;
&#xD;
             i) PR ≥ 210 ms ii) QRS ≥ 120 ms iii) QT ≥ 500 ms iv) QTcF ≥ 450 ms g) Positive urine&#xD;
             screen for drugs of abuse. h) Positive urine alcohol test. i) Positive blood screen&#xD;
             for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human&#xD;
             immunodeficiency virus (HIV)-1 or HIV-2 antibodies at screening.&#xD;
&#xD;
          4. Allergies and Adverse Drug Reaction&#xD;
&#xD;
               1. History of allergy or adverse reactions to DPP4 or SGLT inhibitors or related&#xD;
                  compounds.&#xD;
&#xD;
               2. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).&#xD;
&#xD;
          5. Other Exclusion Criteria&#xD;
&#xD;
               1. Prisoners or subjects who are involuntarily incarcerated.&#xD;
&#xD;
               2. Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
                  physical (eg, infectious disease) illness.&#xD;
&#xD;
               3. Inability to comply with restrictions and prohibited activities/treatments&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Gartner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Celerion</affiliation>
  </overall_official>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <results_first_submitted>February 17, 2016</results_first_submitted>
  <results_first_submitted_qc>March 25, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 27, 2016</results_first_posted>
  <last_update_submitted>March 25, 2016</last_update_submitted>
  <last_update_submitted_qc>March 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 27, 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, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapagliflozin</mesh_term>
    <mesh_term>Saxagliptin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Open-label, randomized, single-dose, 2-treatment, 2-period crossover study in 36 healthy subjects. A single dose was administered on Day 1 and Day 8 under fasted conditions. Blood samples for the plasma pharmacokinetic analysis collected over a 60-hour interval after dosing in each period</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment AB</title>
          <description>Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.&#xD;
Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
        </group>
        <group group_id="P2">
          <title>Treatment BA</title>
          <description>Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.&#xD;
Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment AB</title>
          <description>Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.&#xD;
Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
        </group>
        <group group_id="B2">
          <title>Treatment BA</title>
          <description>Treatment B: Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.&#xD;
Treatment A: Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
        </group>
        <group group_id="B3">
          <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="18"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="36"/>
          </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="33.6" spread="11.63" lower_limit="19" upper_limit="53"/>
                    <measurement group_id="B2" value="32.9" spread="11.34" lower_limit="19" upper_limit="52"/>
                    <measurement group_id="B3" value="33.3" spread="11.32" lower_limit="19" upper_limit="53"/>
                  </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</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </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="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </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/AFRICAN AMERICAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WHITE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Saxagliptin Maximum Observed Concentrations (Cmax)</title>
        <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
        <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
        <population>Evaluable PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Saxagliptin Maximum Observed Concentrations (Cmax)</title>
          <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
          <population>Evaluable PK Population</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.2" spread="5.723" lower_limit="24.6" upper_limit="27.8"/>
                    <measurement group_id="O2" value="25.5" spread="5.763" lower_limit="24.0" upper_limit="27.1"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The specified bioequivalence limits (0.80, 1.25) for PK measures</non_inferiority_desc>
            <p_value>0.4950</p_value>
            <method>ANOVA</method>
            <param_type>Geometric mean ratio</param_type>
            <param_value>0.975</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.915</ci_lower_limit>
            <ci_upper_limit>1.038</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Dapagliflozin Maximum Observed Concentrations (Cmax)</title>
        <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
        <time_frame>Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)</time_frame>
        <population>Evaluable PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Dapagliflozin Maximum Observed Concentrations (Cmax)</title>
          <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
          <population>Evaluable PK Population</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="142" spread="28.93" lower_limit="132" upper_limit="153"/>
                    <measurement group_id="O2" value="141" spread="37.10" lower_limit="132" upper_limit="152"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The specified bioequivalence limits (0.80, 1.25) for PK measures</non_inferiority_desc>
            <p_value>0.8650</p_value>
            <method>ANOVA</method>
            <param_type>Geometric mean ratio</param_type>
            <param_value>0.993</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.932</ci_lower_limit>
            <ci_upper_limit>1.060</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])</title>
        <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
        <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
        <population>Evaluable PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])</title>
          <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
          <population>Evaluable PK Population</population>
          <units>ng.h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.9" spread="5.723" lower_limit="90.0" upper_limit="102"/>
                    <measurement group_id="O2" value="98.0" spread="5.763" lower_limit="92.0" upper_limit="104"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The specified bioequivalence limits (0.80, 1.25) for PK measures</non_inferiority_desc>
            <p_value>0.2344</p_value>
            <method>ANOVA</method>
            <param_type>Geometric mean ratio</param_type>
            <param_value>1.022</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.991</ci_lower_limit>
            <ci_upper_limit>1.054</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])</title>
        <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
        <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
        <population>Evaluable PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])</title>
          <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
          <population>Evaluable PK Population</population>
          <units>ng.h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="537" spread="5.723" lower_limit="504" upper_limit="573"/>
                    <measurement group_id="O2" value="546" spread="5.763" lower_limit="512" upper_limit="582"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The specified bioequivalence limits (0.80, 1.25) for PK measures</non_inferiority_desc>
            <p_value>0.2458</p_value>
            <method>ANOVA</method>
            <param_type>Geometric mean ratio</param_type>
            <param_value>1.016</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.993</ci_lower_limit>
            <ci_upper_limit>1.038</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])</title>
        <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
        <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
        <population>Evaluable PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])</title>
          <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
          <population>Evaluable PK Population</population>
          <units>ng.h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.0" spread="5.723" lower_limit="91.1" upper_limit="103"/>
                    <measurement group_id="O2" value="99.4" spread="5.763" lower_limit="93.3" upper_limit="106"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The specified bioequivalence limits (0.80, 1.25) for PK measures</non_inferiority_desc>
            <p_value>0.1947</p_value>
            <method>ANOVA</method>
            <param_type>Geometric mean ratio</param_type>
            <param_value>1.024</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.993</ci_lower_limit>
            <ci_upper_limit>1.056</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])</title>
        <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
        <time_frame>Day 1-3 (Period 1) and Day 8-10 (Period 2)</time_frame>
        <population>Evaluable PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])</title>
          <description>5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state</description>
          <population>Evaluable PK Population</population>
          <units>ng.h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="553" spread="5.723" lower_limit="518" upper_limit="591"/>
                    <measurement group_id="O2" value="561" spread="5.763" lower_limit="525" upper_limit="599"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The specified bioequivalence limits (0.80, 1.25) for PK measures</non_inferiority_desc>
            <p_value>0.3191</p_value>
            <method>ANOVA</method>
            <param_type>Geometric mean ratio</param_type>
            <param_value>1.013</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.992</ci_lower_limit>
            <ci_upper_limit>1.034</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Treatment A</title>
          <description>Single oral dose of 5-mg saxagliptin tablet coadministered with 10-mg dapagliflozin tablet under fasted conditions.</description>
        </group>
        <group group_id="E2">
          <title>Treatment B</title>
          <description>Single oral dose of 5-mg saxagliptin/10-mg dapagliflozin FDC tablet under fasted conditions.</description>
        </group>
      </group_list>
      <serious_events>
        <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="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Eva Johnsson, Clinical Science Lead, GLOBAL_MEDICINES_DEV</name_or_title>
      <organization>AstraZeneca AB, S-151 85 Södertälje, Sweden</organization>
      <phone>+46 31 7762484 ext 762 484</phone>
      <email>Eva.Johnsson@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/NCT02223065
org study id: CV181-364
nct id: NCT02223065
lead sponsor: 
has dmc: No
The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy
      subjects.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Saxagliptin Maximum Observed Concentrations (Cmax)
time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)
description: 5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
measure: Dapagliflozin Maximum Observed Concentrations (Cmax)
time frame: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)
description: 5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
measure: Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)
description: 5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
measure: Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)
description: 5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
measure: Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)
description: 5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
measure: Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)
description: 5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
arm group label: Treatment A
arm group type: Experimental
description: Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet
arm group label: Treatment B
arm group type: Experimental
description: Single oral dose of FDC (fixed-dose combination) tablet
intervention type: Drug
intervention name: Saxagliptin
arm group label: Treatment A
arm group label: Treatment B
other name: Onglyza
intervention type: Drug
intervention name: Dapagliflozin
arm group label: Treatment A
arm group label: Treatment B
other name: Farxiga in the United States
other name: Forxiga in other countries
criteria: 
gender: All
minimum age: 19 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael Gartner, MD
role: Principal Investigator
affiliation: Celerion
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
mesh term: Dapagliflozin
mesh term: Saxagliptin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 