<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/NCT02209454</url>
  </required_header>
  <id_info>
    <org_study_id>RD 303/25652(DKP-BE-SOL)</org_study_id>
    <secondary_id>2014-000371-10</secondary_id>
    <nct_id>NCT02209454</nct_id>
  </id_info>
  <brief_title>Comparative Bioavailability of Dexketoprofen Trometamol Oral Solution vs Tablet Formulations</brief_title>
  <official_title>Comparative Study of the Bioavailability of Dexketoprofen Trometamol Following Single Doses of 25mg Enantyum® Oral Solution vs. Keral® Tablets in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Menarini Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Simbec Research</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Menarini Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the bioavailability of 25 mg DKP.TRIS given as an&#xD;
      Enantyum® oral solution (Test formulation) and Keral® tablet (Reference formulation). In&#xD;
      addition, this study intends to evaluate the safety and tolerability of Test and Reference&#xD;
      formulations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study was conducted in 1 site and included 26 successfully screened and randomized&#xD;
      healthy subjects(12 female and 14 male).&#xD;
&#xD;
      The study consisted of:&#xD;
&#xD;
        -  Screening Visit (performed within 3 weeks prior to 1st PK study session), for the&#xD;
           evaluation of study eligibility.&#xD;
&#xD;
        -  Two pharmacokinetic (PK) study sessions, separated by a minimum of a 7 day washout&#xD;
           period, including the administration of one out of 2 study treatments at each study&#xD;
           session (namely 25mg DKP.TRIS given as Enantyum® oral solution or Keral® tablet)&#xD;
           according to the sequence as per randomisation list, and blood sampling for PK&#xD;
           assessment on plasma at pre-defined time up to 24 hours post-dose.&#xD;
&#xD;
        -  End of Study Visit (7-10 days after last treatment administration).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">May 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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
    <description>The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 133.00% for Cmax.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t)</measure>
    <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
    <description>The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 125.00% for AUC(0-t).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC(0-∞)</measure>
    <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
    <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
    <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2</measure>
    <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
    <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Acute Pain</condition>
  <arm_group>
    <arm_group_label>Enantyum® oral solution</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>25mg DKP.TRIS oral solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Keral® tablet</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>25mg DKP.TRIS tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enantyum® oral solution</intervention_name>
    <description>One dose of 25 mg DKP oral solution</description>
    <arm_group_label>Enantyum® oral solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Keral® tablet</intervention_name>
    <description>One dose of 25 mg DKP tablet</description>
    <arm_group_label>Keral® tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Healthy male and female subjects between 18 to 50 years old, with a Body Mass Index (BMI)&#xD;
        between 18 Kg/m2 and 28 Kg/m2-&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of previous allergy idiosyncrasy / sensitivity to DKP.TRIS or other NSAIDs&#xD;
             (aspirin, ibuprofen etc).&#xD;
&#xD;
          -  Any condition which might interfere with the absorption, distribution, metabolism or&#xD;
             excretion of the drugs.&#xD;
&#xD;
          -  Surgery within previous 6 months, or blood loss &gt; 400 mL within previous 3 months.&#xD;
&#xD;
          -  Subject with positive human immunodeficiency virus (HIV), hepatitis B surface antigen&#xD;
             (Hep B) and hepatitis C virus antibody (Hep C) results.&#xD;
&#xD;
          -  History of clinically significant alcohol, medicine or drug abuse.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Girish Sharma, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Simbec Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Simbec Research Limited</name>
      <address>
        <city>Merthyr Tydfil</city>
        <state>UK</state>
        <zip>CF48 4DR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <results_first_submitted>May 27, 2015</results_first_submitted>
  <results_first_submitted_qc>June 16, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 9, 2015</results_first_posted>
  <last_update_submitted>June 16, 2015</last_update_submitted>
  <last_update_submitted_qc>June 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 9, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dexketoprofen</keyword>
  <keyword>Bioavailability</keyword>
  <keyword>Comparative</keyword>
  <keyword>Pharmacokinetic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexketoprofen trometamol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Reference IMP First, Then Test IMP</title>
          <description>25mg DKP.TRIS tablet one single administration in first period and 25mg DKP.TRIS oral solution one single administration in second period (after washout period).</description>
        </group>
        <group group_id="P2">
          <title>Test IMP First, Then Reference IMP</title>
          <description>25mg DKP.TRIS oral solution one single administration in first period and 25mg DKP.TRIS tablet one single administration in second period (after washout period).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </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>
          <title>Washout Period a Minimum of a 7 Day</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </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>
          <title>Second Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Twenty-six (26) subjects were randomized (14 male and 12 female) for 24 to complete the study. A total of 25 subjects (13 male and 12 female) completed the study. NOTE: Treatments were administered in a crossover manner, with the same population but one healthy subjects being exposed to the Reference and Test IMP.</population>
      <group_list>
        <group group_id="B1">
          <title>Entire Study Population</title>
          <description>Includes groups randomized to receive 25mg DKP.TRIS tablet first and 25mg DKP.TRIS oral solution first.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
          </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="28.9" spread="6.39"/>
                  </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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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 Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cmax</title>
        <description>The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 133.00% for Cmax.</description>
        <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
        <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
        <group_list>
          <group group_id="O1">
            <title>Enantyum® Oral Solution</title>
            <description>25mg DKP.TRIS oral solution&#xD;
Enantyum® oral solution: One dose of 25 mg DKP oral solution</description>
          </group>
          <group group_id="O2">
            <title>Keral® Tablet</title>
            <description>25mg DKP.TRIS tablet&#xD;
Keral® tablet: One dose of 25 mg DKP tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax</title>
          <description>The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 133.00% for Cmax.</description>
          <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3290.70" lower_limit="2996.00" upper_limit="3614.40"/>
                    <measurement group_id="O2" value="2785.90" lower_limit="2493.20" upper_limit="3113.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-∞)</title>
        <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.</description>
        <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
        <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
        <group_list>
          <group group_id="O1">
            <title>Enantyum® Oral Solution</title>
            <description>25mg DKP.TRIS oral solution&#xD;
Enantyum® oral solution: One dose of 25 mg DKP oral solution</description>
          </group>
          <group group_id="O2">
            <title>Keral® Tablet</title>
            <description>25mg DKP.TRIS tablet&#xD;
Keral® tablet: One dose of 25 mg DKP tablet</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-∞)</title>
          <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.</description>
          <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3473.00" lower_limit="3087.70" upper_limit="3906.40"/>
                    <measurement group_id="O2" value="3485.60" lower_limit="3135.30" upper_limit="3875.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC(0-t)</title>
        <description>The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 125.00% for AUC(0-t).</description>
        <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
        <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
        <group_list>
          <group group_id="O1">
            <title>Enantyum® Oral Solution</title>
            <description>25mg DKP.TRIS oral solution&#xD;
Enantyum® oral solution: One dose of 25 mg DKP oral solution</description>
          </group>
          <group group_id="O2">
            <title>Keral® Tablet</title>
            <description>25mg DKP.TRIS tablet&#xD;
Keral® tablet: One dose of 25 mg DKP tablet</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-t)</title>
          <description>The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 125.00% for AUC(0-t).</description>
          <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3362.20" lower_limit="2986.20" upper_limit="3785.60"/>
                    <measurement group_id="O2" value="3372.00" lower_limit="3027.30" upper_limit="3755.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax</title>
        <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax).</description>
        <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
        <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
        <group_list>
          <group group_id="O1">
            <title>Enantyum® Oral Solution</title>
            <description>25mg DKP.TRIS oral solution&#xD;
Enantyum® oral solution: One dose of 25 mg DKP oral solution</description>
          </group>
          <group group_id="O2">
            <title>Keral® Tablet</title>
            <description>25mg DKP.TRIS tablet&#xD;
Keral® tablet: One dose of 25 mg DKP tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax</title>
          <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax).</description>
          <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" lower_limit="0.17" upper_limit="0.67"/>
                    <measurement group_id="O2" value="0.50" lower_limit="0.25" upper_limit="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>t1/2</title>
        <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.</description>
        <time_frame>Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).</time_frame>
        <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
        <group_list>
          <group group_id="O1">
            <title>Enantyum® Oral Solution</title>
            <description>25mg DKP.TRIS oral solution&#xD;
Enantyum® oral solution: One dose of 25 mg DKP oral solution</description>
          </group>
          <group group_id="O2">
            <title>Keral® Tablet</title>
            <description>25mg DKP.TRIS tablet&#xD;
Keral® tablet: One dose of 25 mg DKP tablet</description>
          </group>
        </group_list>
        <measure>
          <title>t1/2</title>
          <description>AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.</description>
          <population>Analyses of the primary PK variables were conducted on all randomised subjects who received at least one dose of DKP.TRIS (PK population) and on all subjects in the PK population who did not experience major protocol violations (PP population).</population>
          <units>h</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.34" lower_limit="1.23" upper_limit="1.45"/>
                    <measurement group_id="O2" value="1.30" lower_limit="1.20" upper_limit="1.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>from Screening Visit to End of Study Visit</time_frame>
      <desc>Analyzed for the safety population (All subject receiving at least one administration of study treatment)</desc>
      <group_list>
        <group group_id="E1">
          <title>Enantyum® Oral Solution</title>
          <description>25mg DKP.TRIS oral solution&#xD;
Enantyum® oral solution: One dose of 25 mg DKP oral solution</description>
        </group>
        <group group_id="E2">
          <title>Keral® Tablet</title>
          <description>25mg DKP.TRIS tablet&#xD;
Keral® tablet: One dose of 25 mg DKP tablet</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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="4" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Serum ferritin decreases</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </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>Corporate Director of Clinical Research</name_or_title>
      <organization>Menarini Ricerche S.p.A.</organization>
      <phone>0555680 ext 9990</phone>
      <email>acapriati@menarini-ricerche.it</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/NCT02209454
org study id: RD 303/25652(DKP-BE-SOL)
secondary id: 2014-000371-10
nct id: NCT02209454
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to compare the bioavailability of 25 mg DKP.TRIS given as an
      Enantyum® oral solution (Test formulation) and Keral® tablet (Reference formulation). In
      addition, this study intends to evaluate the safety and tolerability of Test and Reference
      formulations.
The study was conducted in 1 site and included 26 successfully screened and randomized
      healthy subjects(12 female and 14 male).

      The study consisted of:

        -  Screening Visit (performed within 3 weeks prior to 1st PK study session), for the
           evaluation of study eligibility.

        -  Two pharmacokinetic (PK) study sessions, separated by a minimum of a 7 day washout
           period, including the administration of one out of 2 study treatments at each study
           session (namely 25mg DKP.TRIS given as Enantyum® oral solution or Keral® tablet)
           according to the sequence as per randomisation list, and blood sampling for PK
           assessment on plasma at pre-defined time up to 24 hours post-dose.

        -  End of Study Visit (7-10 days after last treatment administration).
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Cmax
time frame: Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).
description: The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 133.00% for Cmax.
measure: AUC(0-t)
time frame: Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).
description: The absence of any difference in the rate and extent of absorption will be demonstrated if the 90% CI for the geometric mean ratio between Test and Reference formulations is within the range 80.00% - 125.00% for AUC(0-t).
measure: AUC(0-∞)
time frame: Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).
description: AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.
measure: Tmax
time frame: Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).
description: AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax).
measure: t1/2
time frame: Up to 24h post-dose (pre-dose, T+5', T+10', T+15', T+20', T+30', T+40', T+50', T+1h, T+1.25h, T+1.5h, T+2h, T+3h, T+3.5h, T+4h, T+5h, T+6h, T+8h, T+12h and T+24h post-dose).
description: AUC(0-∞) will be analysed similarly to AUC(0-t) and Cmax. Time to achieve maximum plasma concentration (tmax) and t1/2 will be summarized descriptively.
arm group label: Enantyum® oral solution
arm group type: Other
description: 25mg DKP.TRIS oral solution
arm group label: Keral® tablet
arm group type: Other
description: 25mg DKP.TRIS tablet
intervention type: Drug
intervention name: Enantyum® oral solution
description: One dose of 25 mg DKP oral solution
arm group label: Enantyum® oral solution
intervention type: Drug
intervention name: Keral® tablet
description: One dose of 25 mg DKP tablet
arm group label: Keral® tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Girish Sharma, MBBS
role: Principal Investigator
affiliation: Simbec Research
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Acute Pain
mesh term: Dexketoprofen trometamol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 