<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/NCT03286829</url>
  </required_header>
  <id_info>
    <org_study_id>TM003</org_study_id>
    <nct_id>NCT03286829</nct_id>
  </id_info>
  <brief_title>Study to Investigate the Pharmacokinetic Profile</brief_title>
  <official_title>A Randomized, Open-label, Single-dose, Parallel-arm, Phase 1 Study to Investigate the Pharmacokinetic Profile of a Fixed-Dose Combination Tablet of Tesofensine and Metoprolol (Tesomet) and Co-Administration of Tesofensine Plus Commercial Metoprolol in Adult Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Saniona</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Saniona</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, open-label, single-dose, parallel-arm, Phase 1 study to investigate the&#xD;
      pharmacokinetic profile of a fixed-dose combination tablet of tesofensine and metoprolol&#xD;
      (Tesomet) and co-administration of tesofensine plus commercial metoprolol in adult healthy&#xD;
      subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, parallel-arm study in 60 healthy male subjects who meet the&#xD;
      inclusion and none of the exclusion criteria for the study. Each subject will participate in&#xD;
      a screening period, a baseline period (the day preceding drug administration), and a&#xD;
      single-dose treatment period with an on-site observation period of at least 48 hours after&#xD;
      the dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2017</start_date>
  <completion_date type="Actual">February 6, 2018</completion_date>
  <primary_completion_date type="Actual">February 6, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-48</measure>
    <time_frame>Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose</time_frame>
    <description>Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose</time_frame>
    <description>Maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose</time_frame>
    <description>Time of maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy Male Subjects</condition>
  <arm_group>
    <arm_group_label>Tesomet &quot;High dose&quot; in fasted condition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tesomet &quot;Low dose&quot; in fasted condition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment B (Test 2): A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comperator</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tesomet &quot;High dose&quot; in fed condition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tesomet &quot;High dose&quot; in fasted condition</intervention_name>
    <description>To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.</description>
    <arm_group_label>Comperator</arm_group_label>
    <arm_group_label>Tesomet &quot;High dose&quot; in fed condition</arm_group_label>
    <other_name>Tesofensine</other_name>
    <other_name>Metoprolol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tesomet &quot;Low dose&quot; in fasted condition</intervention_name>
    <description>To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.</description>
    <arm_group_label>Comperator</arm_group_label>
    <other_name>Tesofensine</other_name>
    <other_name>Metoprolol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.</intervention_name>
    <description>To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.</description>
    <arm_group_label>Tesomet &quot;High dose&quot; in fasted condition</arm_group_label>
    <arm_group_label>Tesomet &quot;High dose&quot; in fed condition</arm_group_label>
    <arm_group_label>Tesomet &quot;Low dose&quot; in fasted condition</arm_group_label>
    <other_name>Tesofensine</other_name>
    <other_name>Metoprolol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tesomet &quot;High dose&quot; in fed condition</intervention_name>
    <description>To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.</description>
    <arm_group_label>Comperator</arm_group_label>
    <other_name>Tesofensine</other_name>
    <other_name>Metoprolol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject voluntarily agrees to participate in this study and signs an Independent&#xD;
             Ethics Committee (IEC)-approved informed consent prior to performing any of the&#xD;
             Screening Visit procedures.&#xD;
&#xD;
          2. Males between 18 to 55 years of age, inclusive, at the Screening Visit.&#xD;
&#xD;
          3. Nonsmokers (or other nicotine use) as determined by history (no nicotine use over the&#xD;
             past 6 months) and by urine cotinine concentration (&lt; 500 ng/mL) at the Screening&#xD;
             Visit and admission.&#xD;
&#xD;
          4. BMI between 18.5 and 30.0 kg/m2, inclusive, at the Screening Visit.&#xD;
&#xD;
          5. Healthy, determined by pre-study medical evaluation (medical history, physical&#xD;
             examination, vital signs, 12-lead ECG and clinical laboratory evaluations).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has history or evidence of any clinically significant cardiovascular,&#xD;
             gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic,&#xD;
             urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major&#xD;
             disease or malignancy as judged by the Investigator.&#xD;
&#xD;
          2. Subject has any disorder that would interfere with the absorption, distribution,&#xD;
             metabolism or excretion of drugs.&#xD;
&#xD;
          3. Subject has history of alcohol and/or illicit drug abuse within 2 years of entry.&#xD;
&#xD;
          4. Subject is unwilling to avoid consumption of coffee and caffeine-containing beverages&#xD;
             within 48 hours prior to admission until discharge from the clinical site.&#xD;
&#xD;
          5. Subject is unwilling to avoid use of alcohol or alcohol-containing foods, medications&#xD;
             or beverages, within 48 hours prior to admission until discharge from the clinical&#xD;
             site.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jorgen Drejer, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Saniona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Early Phase Clinical Unit;Klinikum Westend, Haus 31</name>
      <address>
        <city>Berlin</city>
        <zip>14050</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>April 21, 2020</results_first_submitted>
  <results_first_submitted_qc>May 4, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 14, 2020</results_first_posted>
  <last_update_submitted>May 4, 2020</last_update_submitted>
  <last_update_submitted_qc>May 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metoprolol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03286829/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03286829/ICF_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03286829/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tesomet &quot;High Dose&quot; in Fasted Condition</title>
          <description>A Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
        </group>
        <group group_id="P2">
          <title>Tesomet &quot;Low Dose&quot; in Fasted Condition</title>
          <description>A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
        </group>
        <group group_id="P3">
          <title>Comparator</title>
          <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
        </group>
        <group group_id="P4">
          <title>Tesomet &quot;High Dose&quot; in Fed Condition</title>
          <description>A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tesomet &quot;High Dose&quot; in Fasted Condition</title>
          <description>Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
        </group>
        <group group_id="B2">
          <title>Tesomet &quot;Low Dose&quot; in Fasted Condition</title>
          <description>Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
        </group>
        <group group_id="B3">
          <title>Comparator</title>
          <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
        </group>
        <group group_id="B4">
          <title>Tesomet &quot;High Dose&quot; in Fed Condition</title>
          <description>Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</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="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.3" spread="11.55"/>
                    <measurement group_id="B2" value="41.1" spread="8.81"/>
                    <measurement group_id="B3" value="39.5" spread="10.19"/>
                    <measurement group_id="B4" value="41.9" spread="9.91"/>
                    <measurement group_id="B5" value="40.7" spread="9.93"/>
                  </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="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>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="60"/>
                  </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="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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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="0"/>
                    <measurement group_id="B5" value="1"/>
                  </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="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </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="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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="59"/>
                  </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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC0-48</title>
        <description>Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule</description>
        <time_frame>Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tesomet &quot;High Dose&quot; in Fasted Condition</title>
            <description>Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
          </group>
          <group group_id="O2">
            <title>Tesomet &quot;Low Dose&quot; in Fasted Condition</title>
            <description>Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
          </group>
          <group group_id="O3">
            <title>Comparator</title>
            <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
          </group>
          <group group_id="O4">
            <title>Tesomet &quot;High Dose&quot; in Fed Condition</title>
            <description>A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-48</title>
          <description>Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule</description>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.06" spread="26.9"/>
                    <measurement group_id="O2" value="6.491" spread="25.1"/>
                    <measurement group_id="O3" value="45.89" spread="21.9"/>
                    <measurement group_id="O4" value="30.14" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax</title>
        <description>Maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile</description>
        <time_frame>Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tesomet &quot;High Dose&quot; in Fasted Condition</title>
            <description>Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
          </group>
          <group group_id="O2">
            <title>Tesomet &quot;Low Dose&quot; in Fasted Condition</title>
            <description>A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
          </group>
          <group group_id="O3">
            <title>Comparator</title>
            <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
          </group>
          <group group_id="O4">
            <title>Tesomet &quot;High Dose&quot; in Fed Condition</title>
            <description>A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax</title>
          <description>Maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile</description>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9528" spread="25.5"/>
                    <measurement group_id="O2" value="0.1934" spread="23.6"/>
                    <measurement group_id="O3" value="1.357" spread="23.8"/>
                    <measurement group_id="O4" value="0.8085" spread="17.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax</title>
        <description>Time of maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile</description>
        <time_frame>Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tesomet &quot;High Dose&quot; in Fasted Condition</title>
            <description>A Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
          </group>
          <group group_id="O2">
            <title>Tesomet &quot;Low Dose&quot; in Fasted Condition</title>
            <description>A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
          </group>
          <group group_id="O3">
            <title>Comparator</title>
            <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
          </group>
          <group group_id="O4">
            <title>Tesomet &quot;High Dose&quot; in Fed Condition</title>
            <description>A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax</title>
          <description>Time of maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile</description>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.12" spread="5.98"/>
                    <measurement group_id="O2" value="6.00" spread="5.98"/>
                    <measurement group_id="O3" value="6.00" spread="3.98"/>
                    <measurement group_id="O4" value="8.00" spread="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>38days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tesomet &quot;High Dose&quot; in Fasted Condition</title>
          <description>A Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition (&quot;High&quot; dose)</description>
        </group>
        <group group_id="E2">
          <title>Tesomet &quot;Low Dose&quot; in Fasted Condition</title>
          <description>A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (&quot;Low&quot; dose)</description>
        </group>
        <group group_id="E3">
          <title>Comparator</title>
          <description>1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition</description>
        </group>
        <group group_id="E4">
          <title>Tesomet &quot;High Dose&quot; in Fed Condition</title>
          <description>A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (&quot;High&quot; dose)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3.33</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="3" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>catheter side reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin Lesion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </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>Dr.Kim Krogsgaard, MD, DMSc, CMO</name_or_title>
      <organization>Saniona A/S</organization>
      <phone>+45 20 14 83 84</phone>
      <email>kim.krogsgaard@saniona.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/NCT03286829
org study id: TM003
nct id: NCT03286829
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A randomized, open-label, single-dose, parallel-arm, Phase 1 study to investigate the
      pharmacokinetic profile of a fixed-dose combination tablet of tesofensine and metoprolol
      (Tesomet) and co-administration of tesofensine plus commercial metoprolol in adult healthy
      subjects
This is a randomized, open-label, parallel-arm study in 60 healthy male subjects who meet the
      inclusion and none of the exclusion criteria for the study. Each subject will participate in
      a screening period, a baseline period (the day preceding drug administration), and a
      single-dose treatment period with an on-site observation period of at least 48 hours after
      the dose.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Participant)
measure: AUC0-48
time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
description: Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule
measure: Cmax
time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
description: Maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile
measure: Tmax
time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
description: Time of maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile
arm group label: Tesomet "High dose" in fasted condition
arm group type: Experimental
description: A Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition ("High" dose)
arm group label: Tesomet "Low dose" in fasted condition
arm group type: Experimental
description: Treatment B (Test 2): A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. ("Low" dose)
arm group label: Comperator
arm group type: Active Comparator
description: 1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition
arm group label: Tesomet "High dose" in fed condition
arm group type: Experimental
description: A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition ("High" dose)
intervention type: Drug
intervention name: Tesomet "High dose" in fasted condition
description: To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.
arm group label: Comperator
arm group label: Tesomet "High dose" in fed condition
other name: Tesofensine
other name: Metoprolol
intervention type: Drug
intervention name: Tesomet "Low dose" in fasted condition
description: To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.
arm group label: Comperator
other name: Tesofensine
other name: Metoprolol
intervention type: Drug
intervention name: Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.
description: To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.
arm group label: Tesomet "High dose" in fasted condition
arm group label: Tesomet "High dose" in fed condition
arm group label: Tesomet "Low dose" in fasted condition
other name: Tesofensine
other name: Metoprolol
intervention type: Drug
intervention name: Tesomet "High dose" in fed condition
description: To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.
arm group label: Comperator
other name: Tesofensine
other name: Metoprolol
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jorgen Drejer, PhD
role: Study Director
affiliation: Saniona
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Metoprolol
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 