<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/NCT02224053</url>
  </required_header>
  <id_info>
    <org_study_id>D5160C00010</org_study_id>
    <nct_id>NCT02224053</nct_id>
  </id_info>
  <brief_title>Drug-Drug Interaction Study With AZD9291 and Omeprazole in Healthy Volunteers</brief_title>
  <official_title>A Phase I, Fixed Sequence, Open-label, Study to Assess the Pharmacokinetics of AZD9291 in Healthy Male Volunteers When a Single Oral Dose of AZD9291 80 mg is Administered Alone and in Combination With Omeprazole</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, open-label, 2-period fixed sequence design to evaluate the interaction of&#xD;
      AZD9291 with omeprazole in approximately 50 healthy, adult male volunteers. Volunteers will&#xD;
      receive Treatment A (AZD9291 and omeprazole) in Period 1 and Treatment B (AZD9291 only) in&#xD;
      Period 2. The dose of AZD9291 in Period 1 and the dose of AZD9291 in Period 2 will be&#xD;
      separated by a washout of at least 21 days (the washout will not be more than 5 weeks). The&#xD;
      study will be performed at up to 2 sites in the USA and will assess the effect of omeprazole&#xD;
      (proton pump inhibitor) on AZD9291 exposure&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC of AZD9291</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose</time_frame>
    <description>Area under the plasma concentration-time curve from zero to infinity for AZD9291</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of AZD9291</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma concentration (Cmax).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t)</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from zero extrapolated to o the time of the last quantifiable concentration, AUC(0-t)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-72)</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from time zero to 72 hours, AUC(0-72)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using time to reach maximum plasma concentration, tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tlag</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using lag time before observation of quantifiable analyte concentrations in plasma, tlag</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t(1/2)</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal half-life, t(1/2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal rate constant, λz</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F of AZD9291</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 using the apparent plasma clearance, CL/F</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F of AZD9291</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZD9291 using the apparent volume of distribution, Vz/F</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of AZ5104 and AZ7550</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZ5104 and AZ7550 (metabolites to AZD9291) using the maximum plasma concentration, Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of AZ5104 and AZ7550</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Area under the plasma concentration-time curve from zero to infinity of AZ5104 and AZ7550 (metabolites to AZD9291)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parent to Metabolite Ratios of AZ5104 and AZ7550 Cmax</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZ5104 and AZ7550 Cmax using the parent (AZD9291) to metabolite ratios</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parent to Metabolite Ratios of AZ5104 and AZ7550 AUC</measure>
    <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
    <description>Assessment of the PK of AZ5104 and AZ7550 AUC using the parent (AZD9291) to metabolite ratios</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">136</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>AZD9291 and omeprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sequential treatments of AZD9291 + omeprazole followed by AZD9291 alone, with a washout period in between.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pharmacokinetic sampling - AZD9291</intervention_name>
    <description>Blood sampling to measure AZD9291</description>
    <arm_group_label>AZD9291 and omeprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD9291 tablet dosing</intervention_name>
    <description>AZD9291 80mg tablet taken on Day 5 in Period 1 and Day 1 in Period 2.</description>
    <arm_group_label>AZD9291 and omeprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole tablet dosing</intervention_name>
    <description>Omeprzole taken from Days 1 to 5 in Period 1.</description>
    <arm_group_label>AZD9291 and omeprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pharmacokinetic sampling - AZ5140 and AZ7550</intervention_name>
    <description>Blood samples to measure levels of AZ5140 and AZ7550</description>
    <arm_group_label>AZD9291 and omeprazole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For inclusion in the study volunteers must fulfil the following criteria.&#xD;
&#xD;
          1. Provision of signed and dated informed consent prior to any study-specific procedures.&#xD;
&#xD;
          2. Healthy male volunteers aged 18 to 55 years. (Healthy as determined by medical&#xD;
             history, physical examination, laboratory parameters, ECG, and eye examination&#xD;
             performed before the first administration of investigational product.)&#xD;
&#xD;
          3. Body mass index between 19 and 30 kg/m2, and body weight between 50 kg and 100 kg,&#xD;
             inclusive.&#xD;
&#xD;
          4. Veins suitable for cannulation or repeated venepuncture.&#xD;
&#xD;
          5. Volunteers must be willing to use reliable methods of contraception (condom and&#xD;
             spermicide), even if their partners are postmenopausal, surgically sterile, or using&#xD;
             an effective hormonal method of contraception or intrauterine coil. In addition,&#xD;
             volunteers must agree to continue to take similar contraceptive precautions and avoid&#xD;
             sperm donation for 6 months after the last administration of AZD9291.&#xD;
&#xD;
        Volunteers must not enter the study if any of the following exclusion criteria are&#xD;
        fulfilled:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             and Quintiles staff).&#xD;
&#xD;
          2. Previous enrollment in the present study.&#xD;
&#xD;
          3. History of any clinically significant disease or disorder which, in the opinion of the&#xD;
             Investigator, may either put the healthy volunteer at risk because of participation in&#xD;
             the study, or influence the results or the healthy volunteer's ability to participate&#xD;
             in the study.&#xD;
&#xD;
          4. History or presence of gastrointestinal, hepatic, or renal disease or surgical&#xD;
             procedure or any other condition known to interfere with the absorption, distribution,&#xD;
             metabolism, or excretion of drugs.&#xD;
&#xD;
          5. Any clinically significant abnormalities in physical examination, vital signs (supine&#xD;
             blood pressure &gt;140 mmHg systolic, &gt;90 mmHg diastolic, or pulse rate ≤35 or ≥100 beats&#xD;
             per minute), or clinical laboratory assessment as judged by the Investigator.&#xD;
&#xD;
          6. Acute illness, surgical procedures, or trauma from within 2 weeks before enrollment&#xD;
             until first administration of investigational product (IP).&#xD;
&#xD;
          7. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to&#xD;
             dosing.&#xD;
&#xD;
          8. Volunteers with active malignancy or neoplastic disease in the previous 12 months.&#xD;
&#xD;
          9. A suspected/manifested infection according to International Airline Transportation&#xD;
             Association (IATA) Categories A and B infectious substances.&#xD;
&#xD;
         10. Positive results on screening tests for serum hepatitis B surface antigen (HBsAg),&#xD;
             hepatitis C antibody, or human immunodeficiency virus (HIV).&#xD;
&#xD;
         11. Any clinically important abnormalities in rhythm, conduction, or morphology of resting&#xD;
             ECG, as judged by the Investigator.&#xD;
&#xD;
         12. Known or suspected history of significant drug abuse as judged by the Investigator.&#xD;
&#xD;
         13. Positive screen for drugs of abuse or cotinine (nicotine level above 400 ng/mL) at&#xD;
             screening or positive screen for alcohol, drugs of abuse, or cotinine on admission in&#xD;
             Period 1 or Period 2.&#xD;
&#xD;
         14. History of alcohol abuse or excessive intake of alcohol, defined as regular weekly&#xD;
             intake of greater than 21 units of alcohol in men (Note: 1 unit=25 mL spirits, 125 mL&#xD;
             wine, or 250 mL beer or lager).&#xD;
&#xD;
         15. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as&#xD;
             judged by the Investigator, or history of hypersensitivity to AZD9291, its excipients,&#xD;
             or drugs with a similar chemical structure or class.&#xD;
&#xD;
         16. History of hypersensitivity to omeprazole, its excipients, or drugs with a similar&#xD;
             chemical structure or class.&#xD;
&#xD;
         17. Use of any prescribed or nonprescribed medication, including drugs with hepatic&#xD;
             enzyme-altering properties, such as St John's Wort, antacids, analgesics, herbal&#xD;
             remedies, vitamins, and minerals during the 4 weeks (or longer depending on the&#xD;
             medication's half-life) prior to the first administration of AZD9291 is not permitted.&#xD;
             Occasional use of paracetamol (acetaminophen) and nonsteroidal nasal decongestant is&#xD;
             permitted at the discretion of the Investigator.&#xD;
&#xD;
         18. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,&#xD;
             or other products containing grapefruit or Seville oranges within 7 days of the first&#xD;
             administration of IP.&#xD;
&#xD;
         19. Blood donation within 1 month of screening or any blood donation/blood loss greater&#xD;
             than 500 mL during the 3 months prior to screening.&#xD;
&#xD;
         20. Use of another new chemical entity (defined as a compound which has not been approved&#xD;
             for marketing) or participation in any other clinical study (including methodology&#xD;
             studies where no drugs were given) within 3 months of the first administration of IP&#xD;
             in this study.&#xD;
&#xD;
         21. Current smokers or those who have smoked or used nicotine products within the previous&#xD;
             3 months.&#xD;
&#xD;
         22. Planned inpatient surgery, dental procedure, or hospitalisation during the study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Serban Ghiorghiu, MSD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <results_first_submitted>November 26, 2015</results_first_submitted>
  <results_first_submitted_qc>November 26, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 31, 2015</results_first_posted>
  <last_update_submitted>May 23, 2016</last_update_submitted>
  <last_update_submitted_qc>May 23, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 24, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>oncology, cancer, non small cell lung cancer, anticancer druge, omeprazole, healthy volunteer</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osimertinib</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>First subject enrolled: 3 September 2014 Last Subject Last Visit: 5 January 2015 Study was performed at 2 sites in the USA.</recruitment_details>
      <pre_assignment_details>136 subjects were enrolled (signed informed consent). Subjects were assigned to treatment if they met all the inclusion and none of the exclusion criteria.&#xD;
68 subjects were enolled but failed inclusion/exclusion criteria and so were not eligible to be assigned treatment.&#xD;
The remaining 68 subjects started period 1 and received treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AZD9291 and Omeprazole</title>
          <description>Sequential treatments periods of AZD9291 + omeprazole (including a washout) followed by AZD9291 alone.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>AZD9291 and Omeprazole Co-administration</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Exceeding PK limits after Period 1</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </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>
              <title>Protocol non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>AZD9291 Alone</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AZD9291 and Omeprazole</title>
          <description>Sequential treatments periods of AZD9291 + omeprazole (including a washout) followed by AZD9291 alone.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="68"/>
          </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="34.0" spread="11.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC of AZD9291</title>
        <description>Area under the plasma concentration-time curve from zero to infinity for AZD9291</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>AUC of AZD9291</title>
          <description>Area under the plasma concentration-time curve from zero to infinity for AZD9291</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>nM.h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6690" spread="28.8" lower_limit="2340" upper_limit="10200"/>
                    <measurement group_id="O2" value="6269" spread="37.0" lower_limit="2670" upper_limit="14200"/>
                  </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>Study sized so experiment-wise power for the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being within 80% to 125% was 90% (95% for each parameter). Within subject CV assumed to be 23%. 5% change in exposure also assumed.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>90% CIs of geometric mean ratios being within 80% to 125%</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>106.66</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>100.26</ci_lower_limit>
            <ci_upper_limit>113.46</ci_upper_limit>
            <estimate_desc>AZD9291+omeprazole / AZD9291 alone</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax of AZD9291</title>
        <description>Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma concentration (Cmax).</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax of AZD9291</title>
          <description>Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma concentration (Cmax).</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>nM</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="127.8" spread="26.9" lower_limit="47.6" upper_limit="200"/>
                    <measurement group_id="O2" value="126.1" spread="31.0" lower_limit="49.0" upper_limit="200"/>
                  </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>Study sized so experiment-wise power for the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being within 80% to 125% was 90% (95% for each parameter). Within subject CV assumed to be 23%. 5% change in exposure also assumed.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>90% CIs of geometric mean ratios being within 80% to 125%</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>101.65</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>94.65</ci_lower_limit>
            <ci_upper_limit>109.16</ci_upper_limit>
            <estimate_desc>AZD9291+omeprazole / AZD9291 alone</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-t)</title>
        <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from zero extrapolated to o the time of the last quantifiable concentration, AUC(0-t)</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-t)</title>
          <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from zero extrapolated to o the time of the last quantifiable concentration, AUC(0-t)</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>nM.h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD9291</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6673" lower_limit="2340" upper_limit="10200"/>
                    <measurement group_id="O2" value="6249" lower_limit="2660" upper_limit="14100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="546.5" lower_limit="226" upper_limit="939"/>
                    <measurement group_id="O2" value="539.2" lower_limit="230" upper_limit="1110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="520.0" lower_limit="208" upper_limit="1010"/>
                    <measurement group_id="O2" value="560.0" lower_limit="300" upper_limit="942"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-72)</title>
        <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from time zero to 72 hours, AUC(0-72)</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-72)</title>
          <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from time zero to 72 hours, AUC(0-72)</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>nM.h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD9291</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4404" lower_limit="1710" upper_limit="6410"/>
                    <measurement group_id="O2" value="4106" lower_limit="1760" upper_limit="7530"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="301.5" lower_limit="151" upper_limit="589"/>
                    <measurement group_id="O2" value="304.0" lower_limit="153" upper_limit="540"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="216.5" lower_limit="82.1" upper_limit="398"/>
                    <measurement group_id="O2" value="231.3" lower_limit="100" upper_limit="445"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax</title>
        <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using time to reach maximum plasma concentration, tmax</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax</title>
          <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using time to reach maximum plasma concentration, tmax</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD9291</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="5" upper_limit="48.08"/>
                    <measurement group_id="O2" value="6" lower_limit="3" upper_limit="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="5" upper_limit="72.12"/>
                    <measurement group_id="O2" value="7" lower_limit="4" upper_limit="48.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="5" upper_limit="72.42"/>
                    <measurement group_id="O2" value="10" lower_limit="5" upper_limit="71.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tlag</title>
        <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using lag time before observation of quantifiable analyte concentrations in plasma, tlag</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Tlag</title>
          <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using lag time before observation of quantifiable analyte concentrations in plasma, tlag</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD9291</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="0.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="2.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="0.00" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="2.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="0.00" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>t(1/2)</title>
        <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal half-life, t(1/2)</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>t(1/2)</title>
          <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal half-life, t(1/2)</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD9291</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.99" lower_limit="39.2" upper_limit="77.1"/>
                    <measurement group_id="O2" value="63.60" lower_limit="52.3" upper_limit="80.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.06" lower_limit="31.1" upper_limit="85.4"/>
                    <measurement group_id="O2" value="54.47" lower_limit="34.5" upper_limit="87.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.34" lower_limit="47.0" upper_limit="106"/>
                    <measurement group_id="O2" value="72.16" lower_limit="48.5" upper_limit="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>λz</title>
        <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal rate constant, λz</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>λz</title>
          <description>Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal rate constant, λz</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>1/h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD9291</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.011748" lower_limit="0.00899" upper_limit="0.0177"/>
                    <measurement group_id="O2" value="0.010898" lower_limit="0.00862" upper_limit="0.0132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.013577" lower_limit="0.00812" upper_limit="0.0223"/>
                    <measurement group_id="O2" value="0.012722" lower_limit="0.00790" upper_limit="0.0201"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.009718" lower_limit="0.00656" upper_limit="0.0147"/>
                    <measurement group_id="O2" value="0.009606" lower_limit="0.00677" upper_limit="0.0143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL/F of AZD9291</title>
        <description>Assessment of the PK of AZD9291 using the apparent plasma clearance, CL/F</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>CL/F of AZD9291</title>
          <description>Assessment of the PK of AZD9291 using the apparent plasma clearance, CL/F</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.93" lower_limit="15.6" upper_limit="68.4"/>
                    <measurement group_id="O2" value="25.55" lower_limit="11.3" upper_limit="60.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vz/F of AZD9291</title>
        <description>Assessment of the PK of AZD9291 using the apparent volume of distribution, Vz/F</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Vz/F of AZD9291</title>
          <description>Assessment of the PK of AZD9291 using the apparent volume of distribution, Vz/F</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>L</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2037" lower_limit="1280" upper_limit="3870"/>
                    <measurement group_id="O2" value="2343" lower_limit="1250" upper_limit="5120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax of AZ5104 and AZ7550</title>
        <description>Assessment of the PK of AZ5104 and AZ7550 (metabolites to AZD9291) using the maximum plasma concentration, Cmax</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax of AZ5104 and AZ7550</title>
          <description>Assessment of the PK of AZ5104 and AZ7550 (metabolites to AZD9291) using the maximum plasma concentration, Cmax</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>nM</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.543" spread="26.9" lower_limit="2.73" upper_limit="12.0"/>
                    <measurement group_id="O2" value="5.889" spread="31.0" lower_limit="2.67" upper_limit="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.913" lower_limit="1.68" upper_limit="7.98"/>
                    <measurement group_id="O2" value="4.402" lower_limit="2.04" upper_limit="9.69"/>
                  </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>AZ5104</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>90% CIs of geometric mean ratios being within 80% to 125%</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>94.79</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>88.77</ci_lower_limit>
            <ci_upper_limit>101.21</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AZ7550</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>90% CIs of geometric mean ratios being within 80% to 125%</non_inferiority_desc>
            <param_type>Geomteric mean ratio</param_type>
            <param_value>89.70</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>83.89</ci_lower_limit>
            <ci_upper_limit>95.91</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC of AZ5104 and AZ7550</title>
        <description>Area under the plasma concentration-time curve from zero to infinity of AZ5104 and AZ7550 (metabolites to AZD9291)</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>AUC of AZ5104 and AZ7550</title>
          <description>Area under the plasma concentration-time curve from zero to infinity of AZ5104 and AZ7550 (metabolites to AZD9291)</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>nM.h</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="556.6" spread="28.8" lower_limit="231" upper_limit="948"/>
                    <measurement group_id="O2" value="550.7" spread="37.0" lower_limit="245" upper_limit="1130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7750</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="536.5" lower_limit="231" upper_limit="1020"/>
                    <measurement group_id="O2" value="574.9" lower_limit="309" upper_limit="955"/>
                  </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>AZ5104</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>90% CIs of geometric mean ratios being within 80% to 125%</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>102.32</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>96.87</ci_lower_limit>
            <ci_upper_limit>108.07</ci_upper_limit>
            <estimate_desc>AZD9291+omeprazole / AZD9291 alone</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AZ7550</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>90% CIs of geometric mean ratios being within 80% to 125%</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>94.03</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>89.92</ci_lower_limit>
            <ci_upper_limit>98.33</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Parent to Metabolite Ratios of AZ5104 and AZ7550 Cmax</title>
        <description>Assessment of the PK of AZ5104 and AZ7550 Cmax using the parent (AZD9291) to metabolite ratios</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Parent to Metabolite Ratios of AZ5104 and AZ7550 Cmax</title>
          <description>Assessment of the PK of AZ5104 and AZ7550 Cmax using the parent (AZD9291) to metabolite ratios</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>Ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04335" lower_limit="0.0255" upper_limit="0.0873"/>
                    <measurement group_id="O2" value="0.04671" lower_limit="0.0293" upper_limit="0.0908"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03061" lower_limit="0.0169" upper_limit="0.0530"/>
                    <measurement group_id="O2" value="0.03491" lower_limit="0.0169" upper_limit="0.0708"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Parent to Metabolite Ratios of AZ5104 and AZ7550 AUC</title>
        <description>Assessment of the PK of AZ5104 and AZ7550 AUC using the parent (AZD9291) to metabolite ratios</description>
        <time_frame>PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.</time_frame>
        <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>AZD9291 and Omeprazole Co-administration</title>
            <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>AZD9291 Alone</title>
            <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
          </group>
        </group_list>
        <measure>
          <title>Parent to Metabolite Ratios of AZ5104 and AZ7550 AUC</title>
          <description>Assessment of the PK of AZ5104 and AZ7550 AUC using the parent (AZD9291) to metabolite ratios</description>
          <population>Pharmacokinetic population - all subjects who received at least 1 dose of AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product</population>
          <units>Ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZ5104</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08318" lower_limit="0.0464" upper_limit="0.137"/>
                    <measurement group_id="O2" value="0.08785" lower_limit="0.0587" upper_limit="0.133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AZ7550</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08019" lower_limit="0.0334" upper_limit="0.152"/>
                    <measurement group_id="O2" value="0.09166" lower_limit="0.0424" upper_limit="0.207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs collected from the day prior to first dose of treatment (omeprazole) until the follow up visit, approximately 3 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AZD9291 and Omeprazole Co-administration</title>
          <description>Once daily dosing of omeprazole 40 mg on Days 1 to 5 and AZD9291 80 mg single oral dose on Day 5 (Period 1).</description>
        </group>
        <group group_id="E2">
          <title>AZD9291 Alone</title>
          <description>AZD9291 80 mg single oral dose on Day 1 (Period 2)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 17.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="68"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="47"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4</frequency_threshold>
        <default_vocab>MedDRA Version 17.1</default_vocab>
        <default_assessment>Non-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="8" subjects_at_risk="68"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="68"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="47"/>
              </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 Principal Investigator (PI) agrees to collaborate on the contents and formation of any publication and to pay due consideration to comments and opinions offered. AstraZeneca have 30 days for final manuscript review and may require that submission for publication be delayed in order to file patent application.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Karen So</name_or_title>
      <organization>AstraZeneca</organization>
      <email>ClinicalTrialTransparency@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02224053
org study id: D5160C00010
nct id: NCT02224053
lead sponsor: 
has dmc: No
This is a Phase 1, open-label, 2-period fixed sequence design to evaluate the interaction of
      AZD9291 with omeprazole in approximately 50 healthy, adult male volunteers. Volunteers will
      receive Treatment A (AZD9291 and omeprazole) in Period 1 and Treatment B (AZD9291 only) in
      Period 2. The dose of AZD9291 in Period 1 and the dose of AZD9291 in Period 2 will be
      separated by a washout of at least 21 days (the washout will not be more than 5 weeks). The
      study will be performed at up to 2 sites in the USA and will assess the effect of omeprazole
      (proton pump inhibitor) on AZD9291 exposure
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC of AZD9291
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose
description: Area under the plasma concentration-time curve from zero to infinity for AZD9291
measure: Cmax of AZD9291
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma concentration (Cmax).
measure: AUC(0-t)
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from zero extrapolated to o the time of the last quantifiable concentration, AUC(0-t)
measure: AUC(0-72)
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using area under the plasma concentration curve from time zero to 72 hours, AUC(0-72)
measure: Tmax
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using time to reach maximum plasma concentration, tmax
measure: Tlag
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using lag time before observation of quantifiable analyte concentrations in plasma, tlag
measure: t(1/2)
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal half-life, t(1/2)
measure: λz
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 (parent compound), AZ5104 (metabolite) and AZ7550 (metabolite) using the terminal rate constant, λz
measure: CL/F of AZD9291
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 using the apparent plasma clearance, CL/F
measure: Vz/F of AZD9291
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZD9291 using the apparent volume of distribution, Vz/F
measure: Cmax of AZ5104 and AZ7550
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZ5104 and AZ7550 (metabolites to AZD9291) using the maximum plasma concentration, Cmax
measure: AUC of AZ5104 and AZ7550
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Area under the plasma concentration-time curve from zero to infinity of AZ5104 and AZ7550 (metabolites to AZD9291)
measure: Parent to Metabolite Ratios of AZ5104 and AZ7550 Cmax
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZ5104 and AZ7550 Cmax using the parent (AZD9291) to metabolite ratios
measure: Parent to Metabolite Ratios of AZ5104 and AZ7550 AUC
time frame: PK samples collected in both period 1 and 2 at pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours post AZD9291 dose.
description: Assessment of the PK of AZ5104 and AZ7550 AUC using the parent (AZD9291) to metabolite ratios
arm group label: AZD9291 and omeprazole
arm group type: Experimental
description: Sequential treatments of AZD9291 + omeprazole followed by AZD9291 alone, with a washout period in between.
intervention type: Procedure
intervention name: Pharmacokinetic sampling - AZD9291
description: Blood sampling to measure AZD9291
arm group label: AZD9291 and omeprazole
intervention type: Drug
intervention name: AZD9291 tablet dosing
description: AZD9291 80mg tablet taken on Day 5 in Period 1 and Day 1 in Period 2.
arm group label: AZD9291 and omeprazole
intervention type: Drug
intervention name: Omeprazole tablet dosing
description: Omeprzole taken from Days 1 to 5 in Period 1.
arm group label: AZD9291 and omeprazole
intervention type: Procedure
intervention name: Pharmacokinetic sampling - AZ5140 and AZ7550
description: Blood samples to measure levels of AZ5140 and AZ7550
arm group label: AZD9291 and omeprazole
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Serban Ghiorghiu, MSD
role: Study Director
affiliation: AstraZeneca
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Osimertinib
mesh term: Omeprazole
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 