<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/NCT02993471</url>
  </required_header>
  <id_info>
    <org_study_id>16126</org_study_id>
    <secondary_id>I1F-MC-RHBU</secondary_id>
    <nct_id>NCT02993471</nct_id>
  </id_info>
  <brief_title>A Study of Ixekizumab in Participants With Plaque Psoriasis</brief_title>
  <official_title>Evaluation of the Effect of Ixekizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients With Moderate-to-Severe Plaque Psoriasis</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is known as a &quot;drug interaction study.&quot; The purpose is to learn about how&#xD;
      ixekizumab may affect the blood levels of a mixture of commonly used drugs (caffeine,&#xD;
      omeprazole, warfarin, dextromethorphan, and midazolam) that are metabolized by cytochrome&#xD;
      P450. Each participant will complete two study periods. Participants will take the mixture of&#xD;
      commonly used drugs (plus vitamin K) by mouth on 3 occasions (prior to treatment with&#xD;
      ixekizumab and after 1 and 12 weeks of treatment with ixekizumab). The study will last about&#xD;
      17 weeks, including follow-up. Screening must be completed prior to study start.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 22, 2016</start_date>
  <completion_date type="Actual">November 21, 2017</completion_date>
  <primary_completion_date type="Actual">November 21, 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>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan</measure>
    <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
    <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Psoriasis</condition>
  <arm_group>
    <arm_group_label>Drug Cocktail</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally once in Period 1 (day 1).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug Cocktail + Ixekizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally twice in Period 2 (day 8 and day 85). Ixekizumab administered subcutaneously (SC) on multiple occasions in Period 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug Cocktail</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>Drug Cocktail</arm_group_label>
    <arm_group_label>Drug Cocktail + Ixekizumab</arm_group_label>
    <other_name>Caffeine + Warfarin (plus vitamin K) + Omeprazole + Dextromethorphan + Midazolam</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixekizumab</intervention_name>
    <description>Administered SC</description>
    <arm_group_label>Drug Cocktail + Ixekizumab</arm_group_label>
    <other_name>LY2439821</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females with chronic moderate or severe plaque psoriasis for at least 6&#xD;
             months who are candidates for systemic therapy or phototherapy&#xD;
&#xD;
          -  Men and women of childbearing potential must agree to use a reliable method of birth&#xD;
             control and men may not donate sperm for the duration of the study. Women must test&#xD;
             negative for pregnancy at screening and agree not to become pregnant during the study&#xD;
             and until the first normal period following the end of the study&#xD;
&#xD;
          -  Have a body mass index (BMI) of 18.5 to 40.0 kilograms per square meter (kg/m²),&#xD;
             inclusive, at screening&#xD;
&#xD;
          -  Have greater than or equal to (≥) 10 percent body surface area (BSA) involvement at&#xD;
             screening and first admission to the clinical research unit (CRU)&#xD;
&#xD;
          -  Have both a Static Physicians Global Assessment (sPGA) score of ≥3 and Psoriasis Area&#xD;
             Severity Index (PASI) score ≥12 at screening and first admission to the CRU&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Forms of psoriasis other than chronic plaque-type&#xD;
&#xD;
          -  Pregnant or nursing (lactating women)&#xD;
&#xD;
          -  History of an ongoing, chronic or recurrent infectious disease, or evidence of&#xD;
             tuberculosis infection&#xD;
&#xD;
          -  Have major surgery within 8 weeks prior to first admission to the clinical research&#xD;
             unit or during the study&#xD;
&#xD;
          -  Have a history of lymphoproliferative disease, or signs or symptoms of&#xD;
             lymphoproliferative disease, or have active or history of malignant disease, or have&#xD;
             uncontrolled cerebrocardiovascular or neuropsychiatric disease&#xD;
&#xD;
          -  Require treatment with the cocktail drugs or with inhibitors of cytochrome P450 (CYP)&#xD;
             3A, CYP2C9, CYP2D6, CYP2C19, CYP1A2, or with inducers of CYP3A or CYP1A2, or with&#xD;
             rifampin (inducer of multiple CYPs) or with substrates of CYP3A, CYP2C9, CYP2D6,&#xD;
             CYP2C19, or CYP1A2 with narrow therapeutic indices within 14 days prior to the first&#xD;
             administration of the drug cocktail through the end of Week 12 assessments&#xD;
&#xD;
          -  Have any known allergy or hypersensitivity to any component of the study cocktail or&#xD;
             ixekizumab&#xD;
&#xD;
          -  Have participated in any other study with ixekizumab, secukinumab or brodalumab, or&#xD;
             have been prescribed ixekizumab or secukinumab&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</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>Anaheim Clinical Trials, LLC</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avail Clinical Research LLC</name>
      <address>
        <city>DeLand</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>High Point Clinical Trials Center</name>
      <address>
        <city>High Point</city>
        <state>North Carolina</state>
        <zip>27265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.lillytrialguide.com/en-US/studies/psoriasis/RHBU#?postal=</url>
    <description>Click here for more information about this study: A Study of Ixekizumab in Participants with Plaque Psoriasis</description>
  </link>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <results_first_submitted>November 20, 2018</results_first_submitted>
  <results_first_submitted_qc>November 20, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 12, 2019</results_first_posted>
  <last_update_submitted>November 20, 2018</last_update_submitted>
  <last_update_submitted_qc>November 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psoriasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin K</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Dextromethorphan</mesh_term>
    <mesh_term>Caffeine</mesh_term>
    <mesh_term>Ixekizumab</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
    <mesh_term>Warfarin</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>December 8, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT02993471/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>May 31, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT02993471/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Multicenter, open-label, 2-period, fixed-sequence study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Drug Cocktail /Drug Cocktail + Ixekizumab</title>
          <description>Period 1: Participants received drug cocktail (100 mg Caffeine, 10 mg Warfarin [plus vitamin K], 20 mg Omeprazole, 30 mg Dextromethorphan, and 1 mg Midazolam) administered orally on Day 1. Participants resided at the Clinical Research Unit (CRU) until Day 2, and were discharged following collection of 24-hour pharmacokinetics (PK) samples for the determination of plasma concentrations of the cocktail drugs and metabolites.&#xD;
Period 2: Participants received a 160 mg dose of Ixekizumab during an outpatient visit on Day 1 (3 to 7 days after Day 5 of Period 1) and were admitted to the CRU on Day 7 (±2 days) to receive the drug cocktail on the morning of Day 8 (Week 1). Participants received single 80 mg doses of Ixekizumab at outpatient visits on Day 15 (Week 2), Day 29 (Week 4), Day 43 (Week 6), Day 57 (Week 8), and Day 71 (Week 10). Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg Ixekizumab and the drug cocktail on the following morning (Day 85; Week 12).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1 (Drug Cocktail)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 2 (Drug Cocktail + Ixekizumab)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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 enrolled participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Overall Study</title>
          <description>Participants received drug cocktail and drug cocktail + Ixekizumab.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.8" spread="14.62"/>
                  </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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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>
              <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="2"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </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="0"/>
                  </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam</title>
        <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam)</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>1 mg Midazolam</title>
            <description>Participants received 1 mg of Midazolam on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 1 mg Midazolam</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 1 mg of Midazolam on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W (Once Every Two Weeks) + 1 mg Midazolam</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 1 mg of Midazolam on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam</title>
          <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
          <units>nanogram per milliliter (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="27"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.56" spread="24"/>
                    <measurement group_id="O2" value="4.92" spread="24"/>
                    <measurement group_id="O3" value="4.83" spread="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam</title>
        <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam)</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>1 mg Midazolam</title>
            <description>Participants received 1 mg of Midazolam on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 1 mg Midazolam</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 1 mg of Midazolam on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 1 mg Midazolam</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 1 mg of Midazolam on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam</title>
          <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
          <units>nanogram*hour per milliliter (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="27"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.6" spread="28"/>
                    <measurement group_id="O2" value="15.9" spread="27"/>
                    <measurement group_id="O3" value="15.4" spread="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin</title>
        <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin)</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>10 mg Warfarin</title>
            <description>Participants received 10 mg of Warfarin on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 10 mg Warfarin</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 10 mg of Warfarin on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 10 mg Warfarin</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 10 mg of Warfarin on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin</title>
          <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with 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="27"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="510" spread="26"/>
                    <measurement group_id="O2" value="525" spread="22"/>
                    <measurement group_id="O3" value="510" spread="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin</title>
        <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin)</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>10 mg Warfarin</title>
            <description>Participants received 10 mg of Warfarin on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 10 mg Warfarin</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 10 mg of Warfarin on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 10 mg Warfarin</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 10 mg of Warfarin on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin</title>
          <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
          <units>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="27"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17600" spread="29"/>
                    <measurement group_id="O2" value="17700" spread="31"/>
                    <measurement group_id="O3" value="16200" spread="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan</title>
        <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan)</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>30 mg Dextromethorphan</title>
            <description>Participants received 30 mg of Dextromethorphan on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 30 mg Dextromethorphan</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 30 mg of Dextromethorphan on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 30 mg Dextromethorphan</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 30 mg of Dextromethorphan on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan</title>
          <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with 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="27"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.691" spread="291"/>
                    <measurement group_id="O2" value="0.878" spread="202"/>
                    <measurement group_id="O3" value="0.658" spread="285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan</title>
        <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan)</description>
        <time_frame>Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>30 mg Dextromethorphan</title>
            <description>Participants received 30 mg of Dextromethorphan on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 30 mg Dextromethorphan</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 30 mg of Dextromethorphan on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 30 mg Dextromethorphan</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 30 mg of Dextromethorphan on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan</title>
          <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
          <units>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="25"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.7" spread="254"/>
                    <measurement group_id="O2" value="12.6" spread="225"/>
                    <measurement group_id="O3" value="8.53" spread="273"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole</title>
        <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>20 mg Omeprazole</title>
            <description>Participants received 20 mg of Omeprazole on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 20 mg Omeprazole</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 20 mg of Omeprazole on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 20 mg Omeprazole</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 20 mg of Omeprazole on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole</title>
          <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with 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="27"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Omeprazole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="333" spread="83"/>
                    <measurement group_id="O2" value="340" spread="74"/>
                    <measurement group_id="O3" value="368" spread="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5-Hydroxyomeprazole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148" spread="55"/>
                    <measurement group_id="O2" value="143" spread="57"/>
                    <measurement group_id="O3" value="137" spread="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole</title>
        <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>20 mg Omeprazole</title>
            <description>Participants received 20 mg of Omeprazole on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 20 mg Omeprazole</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 20 mg of Omeprazole on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 20 mg Omeprazole</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 20 mg of Omeprazole on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole</title>
          <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
          <units>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="22"/>
                <count group_id="O2" value="23"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Omeprazole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1060" spread="104"/>
                    <measurement group_id="O2" value="829" spread="129"/>
                    <measurement group_id="O3" value="913" spread="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5-Hydroxyomeprazole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="519" spread="28"/>
                    <measurement group_id="O2" value="475" spread="25"/>
                    <measurement group_id="O3" value="455" spread="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine</title>
        <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine)</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>100 mg Caffeine</title>
            <description>Participants received 100 mg of Caffeine on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 100 mg Caffeine</title>
            <description>Participants received 160 mg dose of ixekizumab on Day 1 and 100 mg of Caffeine on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 100 mg Caffeine</title>
            <description>Participants received 80 mg of ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of ixekizumab and 100 mg of Caffeine on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine</title>
          <description>Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with 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="18"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2230" spread="19"/>
                    <measurement group_id="O2" value="2220" spread="22"/>
                    <measurement group_id="O3" value="2240" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine</title>
        <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine)</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose</time_frame>
        <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>100 mg Caffeine</title>
            <description>Participants received 100 mg of Caffeine on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>160 mg Ixekizumab + 100 mg Caffeine</title>
            <description>Participants received 160 mg dose of Ixekizumab on Day 1 and 100 mg of Caffeine on Day 8 of Period 2.</description>
          </group>
          <group group_id="O3">
            <title>80 mg Ixekizumab Q2W + 100 mg Caffeine</title>
            <description>Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 100 mg of Caffeine on the following morning (Day 85; Week 12) during Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine</title>
          <description>Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine)</description>
          <population>All enrolled participants who received at least 1 dose of study drug with evaluable PK data.</population>
          <units>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="13"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25000" spread="48"/>
                    <measurement group_id="O2" value="22400" spread="57"/>
                    <measurement group_id="O3" value="22400" spread="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up To 89 days</time_frame>
      <desc>All enrolled participants who received at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Drug Cocktail</title>
          <description>Participants received drug cocktail (100 mg Caffeine, 10 mg Warfarin [plus vitamin K], 20 mg Omeprazole, 30 mg Dextromethorphan, and 1 mg Midazolam) administered orally on Day 1 of period 1.</description>
        </group>
        <group group_id="E2">
          <title>Drug Cocktail + Ixekizumab</title>
          <description>Participants received a 160 mg dose of Ixekizumab during an outpatient visit on Day 1 (3 to 7 days after Day 5 of Period 1) and were admitted to the CRU on Day 7 (±2 days) to receive the drug cocktail on the morning of Day 8 (Week 1). Participants received single 80 mg doses of Ixekizumab at outpatient visits on Day 15 (Week 2), Day 29 (Week 4), Day 43 (Week 6), Day 57 (Week 8), and Day 71 (Week 10). Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg Ixekizumab and the drug cocktail on the following morning (Day 85; Week 12).</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="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 19.1</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="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis of male external genital organ</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Psoriasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </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/NCT02993471
org study id: 16126
secondary id: I1F-MC-RHBU
nct id: NCT02993471
lead sponsor: 
has dmc: No
This study is known as a "drug interaction study." The purpose is to learn about how
      ixekizumab may affect the blood levels of a mixture of commonly used drugs (caffeine,
      omeprazole, warfarin, dextromethorphan, and midazolam) that are metabolized by cytochrome
      P450. Each participant will complete two study periods. Participants will take the mixture of
      commonly used drugs (plus vitamin K) by mouth on 3 occasions (prior to treatment with
      ixekizumab and after 1 and 12 weeks of treatment with ixekizumab). The study will last about
      17 weeks, including follow-up. Screening must be completed prior to study start.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
description: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
description: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam)
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin
time frame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose
description: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin
time frame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose
description: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin)
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan
time frame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose
description: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan
time frame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose
description: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan)
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
description: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
description: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
description: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
description: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine)
arm group label: Drug Cocktail
arm group type: Experimental
description: Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally once in Period 1 (day 1).
arm group label: Drug Cocktail + Ixekizumab
arm group type: Experimental
description: Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally twice in Period 2 (day 8 and day 85). Ixekizumab administered subcutaneously (SC) on multiple occasions in Period 2.
intervention type: Drug
intervention name: Drug Cocktail
description: Administered orally
arm group label: Drug Cocktail
arm group label: Drug Cocktail + Ixekizumab
other name: Caffeine + Warfarin (plus vitamin K) + Omeprazole + Dextromethorphan + Midazolam
intervention type: Drug
intervention name: Ixekizumab
description: Administered SC
arm group label: Drug Cocktail + Ixekizumab
other name: LY2439821
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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: 
facility: 
facility: 
country: United States
url: https://www.lillytrialguide.com/en-US/studies/psoriasis/RHBU#?postal=
description: Click here for more information about this study: A Study of Ixekizumab in Participants with Plaque Psoriasis
responsible party type: Sponsor
mesh term: Psoriasis
mesh term: Vitamin K
mesh term: Midazolam
mesh term: Dextromethorphan
mesh term: Caffeine
mesh term: Ixekizumab
mesh term: Omeprazole
mesh term: Warfarin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 