<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/NCT03270644</url>
  </required_header>
  <id_info>
    <org_study_id>16857</org_study_id>
    <secondary_id>H8H-MC-LAHD</secondary_id>
    <nct_id>NCT03270644</nct_id>
  </id_info>
  <brief_title>A Study of Lasmiditan and Propranolol in Healthy Participants</brief_title>
  <official_title>Effect of Lasmiditan on Heart Rate and Blood Pressure in Healthy Subjects Receiving Oral Doses of Propranolol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the effects on heart rate and blood pressure when a single dose of&#xD;
      lasmiditan is administered with a daily dose of propranolol. This study will also measure how&#xD;
      much lasmiditan gets into the bloodstream after taking lasmiditan alone and after taking it&#xD;
      together with propranolol. The study will also look at how well both drugs are tolerated.&#xD;
      Information about any side effects that may occur will be collected.&#xD;
&#xD;
      This study will last approximately 45 days including screening. This study will require 13&#xD;
      days/12 nights in a Clinical Research Unit (CRU) followed by 1 follow-up appointment&#xD;
      approximately 7 days after the last dose. Screening is required within 28 days prior to the&#xD;
      start of the study.&#xD;
&#xD;
      This study is for research purposes only and is not intended to treat any medical condition.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2017</start_date>
  <completion_date type="Actual">November 22, 2017</completion_date>
  <primary_completion_date type="Actual">November 22, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan</measure>
    <time_frame>Baseline (Day 8), Day 9</time_frame>
    <description>Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.</time_frame>
    <description>Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose</time_frame>
    <description>Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.</time_frame>
    <description>AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose</time_frame>
    <description>AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan</measure>
    <time_frame>Baseline (Day 8), Day 9</time_frame>
    <description>Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan</measure>
    <time_frame>Baseline (Day 8), Day 9</time_frame>
    <description>Change from baseline in systolic blood pressure was measured in supine position.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan</measure>
    <time_frame>Baseline (Day 8), Day 9</time_frame>
    <description>Change from baseline in diastolic blood pressure was measured in supine position.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Lasmiditan Reference</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral dose of lasmiditan 200 mg on Day 1 as reference treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Propranolol Reference</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Twice-daily oral doses of propranolol 80 mg on Days 4-10 as reference treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lasmiditan + Propranolol Test</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral dose of lasmiditan 200 mg + two oral doses of propranolol 80 mg on Day 9 as test treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lasmiditan</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>Lasmiditan + Propranolol Test</arm_group_label>
    <arm_group_label>Lasmiditan Reference</arm_group_label>
    <other_name>LY573144</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propranolol</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>Lasmiditan + Propranolol Test</arm_group_label>
    <arm_group_label>Propranolol Reference</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males or females, as determined by medical history and physical examination&#xD;
&#xD;
          -  Have a body mass index (BMI) of 19 to 35 kilograms per meter squared (kg/m²)&#xD;
             inclusive, at the time of screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have known allergies to lasmiditan, propranolol, related compounds or any components&#xD;
             of the formulation of lasmiditan or propranolol&#xD;
&#xD;
          -  Have a history of, or electrocardiogram (ECG) findings of, clinically significant&#xD;
             bradycardia, heart block, tachy or brady arrhythmias, sick sinus syndrome/sinoatrial&#xD;
             block, or second or third-degree heart block, or have any other abnormality in the&#xD;
             12-lead ECG that, in the opinion of the investigator, increases the risks associated&#xD;
             with participating in the study&#xD;
&#xD;
          -  Have an abnormal supine blood pressure, defined as systolic blood pressure less than&#xD;
             (&lt;) 95 or greater than (&gt;) 140 millimeters of mercury (mmHg) or diastolic blood&#xD;
             pressure &lt;65 or &gt;90 mmHg at screening&#xD;
&#xD;
          -  Have a supine pulse rate of &lt;50 or &gt;90 beats per minute (bpm) at screening&#xD;
&#xD;
          -  Have an estimated glomerular filtration rate (eGFR) of &lt;60 milliliter per minute&#xD;
             (mL/min) per 1.73 meter squared (m2)&#xD;
&#xD;
          -  Show evidence of significant active neuropsychiatric disease (for example, manic&#xD;
             depressive illness, schizophrenia, depression)&#xD;
&#xD;
          -  Show a history of central nervous system (CNS) conditions such as strokes, transient&#xD;
             ischaemic attacks, significant head trauma, CNS infections, migraines, brain surgery&#xD;
             or any other neurological conditions that, in the opinion of the investigator,&#xD;
             increases the risk of participating in the study&#xD;
&#xD;
          -  Are women with a positive pregnancy test or women who are lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Daytona Beach</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <results_first_submitted>November 8, 2019</results_first_submitted>
  <results_first_submitted_qc>November 8, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 2, 2019</results_first_posted>
  <last_update_submitted>December 2, 2019</last_update_submitted>
  <last_update_submitted_qc>December 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2019</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>Propranolol</mesh_term>
    <mesh_term>Lasmiditan</mesh_term>
  </intervention_browse>
  <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>October 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03270644/Prot_000.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>November 22, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03270644/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Open-label fixed-sequence study in which participants received a single oral dose of lasmiditan 200 mg on Day (D) 1 Reference Treatment (R), then propranolol 80 mg administered orally twice daily from Day 4 through Day 10 Reference Treatment, with one single oral dose of lasmiditan 200 mg on Day 9 Test Treatment (T).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Lasmiditan (R); Propranolol (R) + Lasmiditan (T)</title>
          <description>Lasmiditan 200 mg single dose administered orally on D 1 (Reference); Propranolol 80 mg administered orally twice daily D4-10(Reference); Lasmiditan 200 mg administered orally on D9 (Test).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Day 1 Lasmiditan Reference</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least One Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Day 4 - 10 Propranolol Reference</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least One Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Day 9 Lasmiditan + Propranolol Test</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Lasmiditan + Propranolol</title>
          <description>Single 200 mg dose of lasmiditan administered orally on Day 1, then 80mg propranolol twice per day administered orally on Days 4 through 10, and 200 mg lasmiditan coadministered orally with propranolol on Day 9.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="44"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.1" spread="12.8"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="32"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Hourly Heart Rate</title>
          <population>All participants who received one dose of study drug and had hourly HR baseline data.</population>
          <units>beats per minute (BPM)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.7" spread="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
        <description>Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.</description>
        <time_frame>Baseline (Day 8), Day 9</time_frame>
        <population>All participants who had at least one dose of study drug and had baseline and post-baseline cardiovascular measurements.</population>
        <group_list>
          <group group_id="O1">
            <title>Propranolol (Reference Treatment)</title>
            <description>Propranolol 80 mg administered orally twice daily on Day 8.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
          <description>Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.</description>
          <population>All participants who had at least one dose of study drug and had baseline and post-baseline cardiovascular measurements.</population>
          <units>beats per minute (bpm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.7" spread="7.1"/>
                    <measurement group_id="O2" value="54.2" spread="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Mean hourly HR was evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Difference of LSMeans</param_type>
            <param_value>-5.45</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.27</ci_lower_limit>
            <ci_upper_limit>-3.64</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol</title>
        <description>Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.</description>
        <time_frame>Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.</time_frame>
        <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lasmiditan (Reference Treatment)</title>
            <description>Lasmiditan 200 mg single dose administered orally on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol</title>
          <description>Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.</description>
          <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
          <units>nanogram per mililiter (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="44"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="323" spread="43"/>
                    <measurement group_id="O2" value="290" spread="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Log-transformed PK parameters were evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric LSMeans</param_type>
            <param_value>0.884</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.832</ci_lower_limit>
            <ci_upper_limit>0.939</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan</title>
        <description>Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.</description>
        <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose</time_frame>
        <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Propranolol (Reference Treatment)</title>
            <description>Propranolol 80 mg administered orally twice daily Day 8.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200mg coadministered with 80 mg propranolol on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan</title>
          <description>Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.</description>
          <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
          <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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="133" spread="52"/>
                    <measurement group_id="O2" value="127" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Ratio of geometric LSMeans of Cmax used a mixed-effects repeated measures model adjusted for fixed effects for treatment, time point, time point by treatment, and random effect for subjects.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric LSMeans</param_type>
            <param_value>0.958</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.917</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol</title>
        <description>AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.</description>
        <time_frame>Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.</time_frame>
        <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lasmiditan (Reference Treatment)</title>
            <description>Lasmiditan 200 mg single dose administered orally on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol</title>
          <description>AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.</description>
          <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
          <units>nanograms * hour/mL (ng*h/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="44"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2100" spread="39"/>
                    <measurement group_id="O2" value="2160" spread="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Log-transformed PK parameters were evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric LSMeans</param_type>
            <param_value>1.01</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.967</ci_lower_limit>
            <ci_upper_limit>1.04</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan</title>
        <description>AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.</description>
        <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose</time_frame>
        <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Propranolol (Reference Treatment)</title>
            <description>Propranolol 80 mg administered orally twice daily on Day 8.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan</title>
          <description>AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.</description>
          <population>All participants who received at least one dose of study drug and have evaluable PK data.</population>
          <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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="910" spread="50"/>
                    <measurement group_id="O2" value="910" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Log-transformed PK parameters were evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric LSMeans</param_type>
            <param_value>0.999</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.967</ci_lower_limit>
            <ci_upper_limit>1.03</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
        <description>Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.</description>
        <time_frame>Baseline (Day 8), Day 9</time_frame>
        <population>All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.</population>
        <group_list>
          <group group_id="O1">
            <title>Propranolol (Reference Treatment)</title>
            <description>Propranolol 80 mg administered orally twice daily on Day 8.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
          <description>Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.</description>
          <population>All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.</population>
          <units>millisecond (msec)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.6" spread="20.5"/>
                    <measurement group_id="O2" value="161.9" spread="20.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>PR interval was evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Difference of LSMeans</param_type>
            <param_value>-3.51</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.39</ci_lower_limit>
            <ci_upper_limit>-0.64</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
        <description>Change from baseline in systolic blood pressure was measured in supine position.</description>
        <time_frame>Baseline (Day 8), Day 9</time_frame>
        <population>All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.</population>
        <group_list>
          <group group_id="O1">
            <title>Propranolol (Reference Treatment)</title>
            <description>Propranolol 80 mg administered orally twice daily on Day 8.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
          <description>Change from baseline in systolic blood pressure was measured in supine position.</description>
          <population>All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.</population>
          <units>millimeters of mercury (mmHg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.9" spread="6.6"/>
                    <measurement group_id="O2" value="112.4" spread="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Systolic blood pressure was evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Difference of LSMeans</param_type>
            <param_value>5.57</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.57</ci_lower_limit>
            <ci_upper_limit>7.57</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
        <description>Change from baseline in diastolic blood pressure was measured in supine position.</description>
        <time_frame>Baseline (Day 8), Day 9</time_frame>
        <population>All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.</population>
        <group_list>
          <group group_id="O1">
            <title>Propranolol (Reference Treatment)</title>
            <description>Propranolol 80 mg administered orally twice daily on Day 8.</description>
          </group>
          <group group_id="O2">
            <title>Lasmiditan + Propranolol (Test Treatment)</title>
            <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan</title>
          <description>Change from baseline in diastolic blood pressure was measured in supine position.</description>
          <population>All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.0" spread="6.2"/>
                    <measurement group_id="O2" value="67.4" spread="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Diastolic blood pressure was evaluated in a linear mixed-effects model with a fixed effect for treatment and a random effect for subject.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Difference of LSMeans</param_type>
            <param_value>3.47</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.99</ci_lower_limit>
            <ci_upper_limit>4.95</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline through study completion (up to 23 days).</time_frame>
      <desc>All participants who have received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Lasmiditan 200 mg (Reference Treatment)</title>
          <description>Lasmiditan 200 mg single dose administered orally on Day 1.</description>
        </group>
        <group group_id="E2">
          <title>Propranolol 80 mg (Reference Treatment)</title>
          <description>Propranolol 80 mg administered orally twice daily on Day 4 to Day 10.</description>
        </group>
        <group group_id="E3">
          <title>Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)</title>
          <description>Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="42"/>
              </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="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Eli Lilly and Company</organization>
      <phone>800-545-5979</phone>
      <email>ClinicalTrials.gov@lilly.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/NCT03270644
org study id: 16857
secondary id: H8H-MC-LAHD
nct id: NCT03270644
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will assess the effects on heart rate and blood pressure when a single dose of
      lasmiditan is administered with a daily dose of propranolol. This study will also measure how
      much lasmiditan gets into the bloodstream after taking lasmiditan alone and after taking it
      together with propranolol. The study will also look at how well both drugs are tolerated.
      Information about any side effects that may occur will be collected.

      This study will last approximately 45 days including screening. This study will require 13
      days/12 nights in a Clinical Research Unit (CRU) followed by 1 follow-up appointment
      approximately 7 days after the last dose. Screening is required within 28 days prior to the
      start of the study.

      This study is for research purposes only and is not intended to treat any medical condition.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan
time frame: Baseline (Day 8), Day 9
description: Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol
time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
description: Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.
measure: Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan
time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
description: Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.
measure: Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol
time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
description: AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.
measure: Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan
time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
description: AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.
measure: Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan
time frame: Baseline (Day 8), Day 9
description: Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.
measure: Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan
time frame: Baseline (Day 8), Day 9
description: Change from baseline in systolic blood pressure was measured in supine position.
measure: Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan
time frame: Baseline (Day 8), Day 9
description: Change from baseline in diastolic blood pressure was measured in supine position.
arm group label: Lasmiditan Reference
arm group type: Experimental
description: Single oral dose of lasmiditan 200 mg on Day 1 as reference treatment.
arm group label: Propranolol Reference
arm group type: Active Comparator
description: Twice-daily oral doses of propranolol 80 mg on Days 4-10 as reference treatment.
arm group label: Lasmiditan + Propranolol Test
arm group type: Experimental
description: Single oral dose of lasmiditan 200 mg + two oral doses of propranolol 80 mg on Day 9 as test treatment.
intervention type: Drug
intervention name: Lasmiditan
description: Administered orally
arm group label: Lasmiditan + Propranolol Test
arm group label: Lasmiditan Reference
other name: LY573144
intervention type: Drug
intervention name: Propranolol
description: Administered orally
arm group label: Lasmiditan + Propranolol Test
arm group label: Propranolol Reference
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
country: United States
responsible party type: Sponsor
mesh term: Propranolol
mesh term: Lasmiditan
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 