<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/NCT03802227</url>
  </required_header>
  <id_info>
    <org_study_id>18-181-26</org_study_id>
    <nct_id>NCT03802227</nct_id>
  </id_info>
  <brief_title>A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.</brief_title>
  <official_title>A Phase 1 Double-Blind, Double-Dummy, Parallel-Group, Randomized, Positive Control Study Using fMRI to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nektar Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nektar Therapeutics</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate the effect of NKTR-181 on brain activity in&#xD;
      healthy, non-physically dependent recreational opioid users. This study will last about 88&#xD;
      days for each participant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a single-center study in which approximately 24 subjects will be randomized to&#xD;
      one of two treatment groups. Subjects will enter a screening period between Day -28 and Day&#xD;
      -2. Upon meeting all criteria for enrollment, on Day -1 subjects will enter the clinical&#xD;
      research study unit (CRSU) for an overnight confinement. On Day 1, subjects will undergo a&#xD;
      baseline MRI and will then be randomized to NKTR-181 or oxycodone immediate release (IR).&#xD;
      Once randomized, subjects will receive a single dose of study drug (NKTR-181 or oxycodone IR)&#xD;
      and matched alternate-treatment placebo. Subjects will undergo a series of three fMRIs&#xD;
      (functional magnetic resonance imaging) post dose (at hours 1, 2, and 4). At post-dose hours&#xD;
      0.5, 1, 2, 3, 4, 5, 6, and 8, pupillometry will be performed and PK blood samples will be&#xD;
      drawn. Following a 14- to 17-day safety follow-up period, subjects will return to the&#xD;
      research facility clinic for the End of Study (EOS) visit (Day 16-19).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor Decision&#xD;
  </why_stopped>
  <start_date type="Actual">October 22, 2018</start_date>
  <completion_date type="Actual">January 3, 2020</completion_date>
  <primary_completion_date type="Actual">December 17, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>A double-blind, double-dummy, parallel-group, randomized, positive control study.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brain Activity Measured Via fMRI</measure>
    <time_frame>8 hour period following dose of NKTR-181</time_frame>
    <description>The primary objective of the study was to evaluate the effects of NKTR-181 on brain activity. Functional MRI assessments in subjects administered opioids such as morphine, buprenorphine, and nalbuphine have shown drug-induced signaling changes in reward structures such as the nucleus accumbens, orbitofrontal cortex, and hippocampus, as well as changes in the functional connectivity of reward circuitry (Becerra, 2006; Gear, 2013; Upadhyay, 2012).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Pupil Diameter Via Pupillometry</measure>
    <time_frame>24 hour period following dose administration Day 1 to 2</time_frame>
    <description>Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Drug Concentration</measure>
    <time_frame>24 hour period following dose administration Day 1 to 2</time_frame>
    <description>Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration (Tmax)</measure>
    <time_frame>24 hour period following dose administration Day 1 to 2</time_frame>
    <description>The amount of time needed for maximum drug concentration to be reached.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>19 days</time_frame>
    <description>Number of patients who experienced any type of adverse event as a result of one of the treatments.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Moderate to Severe Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NKTR-181 400 mg and oxycodone IR placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oxycodone IR 40 mg and NKTR-181 placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NKTR-181</intervention_name>
    <description>A combination of NKTR-181 and oxycodone IR placebo</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone IR</intervention_name>
    <description>A combination of oxycodone IR and NKTR-181 placebo</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female recreational opioid users, 18-65 years of age inclusive.&#xD;
&#xD;
          -  Body Mass Index (BMI) between 19.0 to 45.0kg/m2&#xD;
&#xD;
          -  Have at least one urine drug screen positive for opioids during Screening to confirm&#xD;
             recreational opioid use. Subjects testing positive for methadone or buprenorphine&#xD;
             prescribed for treatment will be excluded.&#xD;
&#xD;
          -  Subjects must agree to practice adequate contraception as outlined in the protocol.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Any metal fragments or other bodily metal that would pose a risk to subjects during&#xD;
             MRI scanning as determined by the MRI technologist and/or MRI physicist&#xD;
&#xD;
          -  Any clinically significant disease or condition that might compromise the&#xD;
             cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous,&#xD;
             or gastrointestinal systems or other conditions that may interfere with the&#xD;
             absorption, distribution, metabolism, or excretion of the study drug or would place&#xD;
             the subject at increased risk&#xD;
&#xD;
          -  History of clinically significant acute asthma or other obstructive airway disease&#xD;
             requiring daily controller medication or any condition that may increase the risk for&#xD;
             respiratory depression&#xD;
&#xD;
          -  Current neurologic conditions such as convulsive disorders, or history of severe head&#xD;
             injury.&#xD;
&#xD;
          -  Any current DSM-5 axis I psychiatric disorder or neurological disorder requiring&#xD;
             ongoing treatment&#xD;
&#xD;
          -  Current substance use disorder (moderate to severe), other than Opioid, Nicotine, THC&#xD;
             (tetrahydrocannabinol), cocaine, or caffeine as defined by DSM-5&#xD;
&#xD;
          -  Physical dependence of opioids&#xD;
&#xD;
          -  History of claustrophobia or any other psychiatric disorder that would preclude&#xD;
             subject tolerance of MRI procedures.&#xD;
&#xD;
          -  Current use of any medication that could affect central nervous system blood flow&#xD;
             (e.g. certain cardiovascular medications, triptan migraine medications)&#xD;
&#xD;
          -  Clinical Opiate Withdrawal Scale (COWS) score of greater than 5 during screening or&#xD;
             prior to first scan.&#xD;
&#xD;
          -  Positive urine drug screen for buprenorphine or methadone immediately prior to the&#xD;
             first scan.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Nektar Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigator Site - Richmond</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <results_first_submitted>December 23, 2020</results_first_submitted>
  <results_first_submitted_qc>May 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 27, 2021</results_first_posted>
  <last_update_submitted>July 6, 2021</last_update_submitted>
  <last_update_submitted_qc>July 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2021</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>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxycodone</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 24, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03802227/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>August 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03802227/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Treatment assignments were based on a computer-generated randomization scheduled prepared by SynteractHCR Inc. prior to study start</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>NKTR-181</title>
          <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR</description>
        </group>
        <group group_id="P2">
          <title>Oxycodone IR 40 mg</title>
          <description>Once capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NKTR-181</title>
          <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR oxycodone IR</description>
        </group>
        <group group_id="B2">
          <title>Oxycodone IR 40 mg</title>
          <description>One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="8"/>
          </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="38.5" spread="7.42"/>
                    <measurement group_id="B2" value="43.5" spread="3.42"/>
                    <measurement group_id="B3" value="41.0" spread="5.98"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height (cm)</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="166.3" spread="5.94"/>
                    <measurement group_id="B2" value="182.0" spread="2.44"/>
                    <measurement group_id="B3" value="174.1" spread="9.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81.5" spread="21.30"/>
                    <measurement group_id="B2" value="83.8" spread="5.93"/>
                    <measurement group_id="B3" value="82.7" spread="14.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI (kg/m2)</title>
          <units>kilograms per meter squared</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.7" spread="8.83"/>
                    <measurement group_id="B2" value="25.3" spread="2.12"/>
                    <measurement group_id="B3" value="27.5" spread="6.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic Blood Pressure (mm Hg)</title>
          <units>millimeters of Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="143.5" spread="11.47"/>
                    <measurement group_id="B2" value="127.3" spread="12.74"/>
                    <measurement group_id="B3" value="135.4" spread="14.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic Blood Pressure (mm Hg)</title>
          <units>millimeters of Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="91.3" spread="18.63"/>
                    <measurement group_id="B2" value="74.5" spread="12.66"/>
                    <measurement group_id="B3" value="82.9" spread="17.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pulse Rate (bpm)</title>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.5" spread="6.40"/>
                    <measurement group_id="B2" value="74.3" spread="4.35"/>
                    <measurement group_id="B3" value="74.4" spread="5.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Respiratory Rate (breaths per minute)</title>
          <units>breaths per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14.0" spread="2.31"/>
                    <measurement group_id="B2" value="17.5" spread="1.00"/>
                    <measurement group_id="B3" value="15.8" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>SpO2 (%)</title>
          <units>%</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="97.3" spread="0.96"/>
                    <measurement group_id="B2" value="97.5" spread="1.91"/>
                    <measurement group_id="B3" value="97.4" spread="1.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Temperature (degrees Celsius)</title>
          <units>degrees Celsius</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.7" spread="0.37"/>
                    <measurement group_id="B2" value="36.8" spread="0.27"/>
                    <measurement group_id="B3" value="36.7" spread="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Brain Activity Measured Via fMRI</title>
        <description>The primary objective of the study was to evaluate the effects of NKTR-181 on brain activity. Functional MRI assessments in subjects administered opioids such as morphine, buprenorphine, and nalbuphine have shown drug-induced signaling changes in reward structures such as the nucleus accumbens, orbitofrontal cortex, and hippocampus, as well as changes in the functional connectivity of reward circuitry (Becerra, 2006; Gear, 2013; Upadhyay, 2012).</description>
        <time_frame>8 hour period following dose of NKTR-181</time_frame>
        <population>Subjects who had sufficient MRI data for NKTR-181 or oxycodone IR treatment to allow for analysis of modulation of brain circuitry.</population>
        <group_list>
          <group group_id="O1">
            <title>NKTR-181</title>
            <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR</description>
          </group>
          <group group_id="O2">
            <title>Oxycodone IR 40 mg</title>
            <description>One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Activity Measured Via fMRI</title>
          <description>The primary objective of the study was to evaluate the effects of NKTR-181 on brain activity. Functional MRI assessments in subjects administered opioids such as morphine, buprenorphine, and nalbuphine have shown drug-induced signaling changes in reward structures such as the nucleus accumbens, orbitofrontal cortex, and hippocampus, as well as changes in the functional connectivity of reward circuitry (Becerra, 2006; Gear, 2013; Upadhyay, 2012).</description>
          <population>Subjects who had sufficient MRI data for NKTR-181 or oxycodone IR treatment to allow for analysis of modulation of brain circuitry.</population>
          <units>Correlation Coefficient</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Effective Connectivity between ACC and R Hippocampus at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.12"/>
                    <measurement group_id="O2" value="0.2" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between ACC and R Hippocampus after 1 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.28"/>
                    <measurement group_id="O2" value="0.0" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between ACC and R Hippocampus after 2 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.20"/>
                    <measurement group_id="O2" value="-0.1" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between ACC and R Hippocampus after 4 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.20"/>
                    <measurement group_id="O2" value="0.0" spread="0.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between ACC and R Hippocampus after 8 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.02"/>
                    <measurement group_id="O2" value="0.2" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between R Amygdala and mPFC at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.38"/>
                    <measurement group_id="O2" value="0.0" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between R Amygdala and mPFC after 1 hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="0.41"/>
                    <measurement group_id="O2" value="0.1" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between R Amygdala and mPFC after 2 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.21"/>
                    <measurement group_id="O2" value="0.4" spread="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between R Amygdala and mPFC after 4 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.26"/>
                    <measurement group_id="O2" value="0.1" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effective Connectivity between R Amygdala and mPFC after 8 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.54"/>
                    <measurement group_id="O2" value="0.1" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Pupil Diameter Via Pupillometry</title>
        <description>Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.</description>
        <time_frame>24 hour period following dose administration Day 1 to 2</time_frame>
        <population>Subjects who received at least one dose of NKTR-181 or oxycodone IR and did not have unexpected pupillary dilation as a result of technical issues during the procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>NKTR-181</title>
            <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR</description>
          </group>
          <group group_id="O2">
            <title>Oxycodone IR 40 mg</title>
            <description>One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pupil Diameter Via Pupillometry</title>
          <description>Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.</description>
          <population>Subjects who received at least one dose of NKTR-181 or oxycodone IR and did not have unexpected pupillary dilation as a result of technical issues during the procedure.</population>
          <units>millimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Pupil Diameter</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.45" spread="1.198"/>
                    <measurement group_id="O2" value="4.81" spread="1.717"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 1 Hour</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.03" spread="0.443"/>
                    <measurement group_id="O2" value="4.87" spread="1.624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 2 Hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.82" spread="1.550"/>
                    <measurement group_id="O2" value="4.97" spread="1.747"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 4 Hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.34" spread="0.985"/>
                    <measurement group_id="O2" value="5.32" spread="1.723"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 6 Hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.99" spread="2.213"/>
                    <measurement group_id="O2" value="5.01" spread="1.086"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 8 Hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.28" spread="1.161"/>
                    <measurement group_id="O2" value="5.07" spread="1.115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 12 Hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.91" spread="NA">There is only one participant</measurement>
                    <measurement group_id="O2" value="3.87" spread="NA">There is only one participant</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pupil Diameter After 24 Hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.61" spread="0.403"/>
                    <measurement group_id="O2" value="4.20" spread="0.191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Drug Concentration</title>
        <description>Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.</description>
        <time_frame>24 hour period following dose administration Day 1 to 2</time_frame>
        <population>Consisted of all subjects who had sufficient plasma concentration data to facilitate the calculation of maximum plasma drug concentration as determined by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>NKTR-181</title>
            <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR</description>
          </group>
          <group group_id="O2">
            <title>Oxycodone IR 40 mg</title>
            <description>One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Drug Concentration</title>
          <description>Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.</description>
          <population>Consisted of all subjects who had sufficient plasma concentration data to facilitate the calculation of maximum plasma drug concentration as determined by the pharmacokineticist.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Plasma Drug Concentration at Hour 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1970" spread="477"/>
                    <measurement group_id="O2" value="35.7" spread="33.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2360" spread="1230"/>
                    <measurement group_id="O2" value="54.1" spread="13.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1350" spread="656"/>
                    <measurement group_id="O2" value="46.7" spread="15.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="388" spread="230"/>
                    <measurement group_id="O2" value="27.1" spread="7.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="185" spread="30.4"/>
                    <measurement group_id="O2" value="14.8" spread="NA">Only one sample was collected for this measurement</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.5" spread="13.7"/>
                    <measurement group_id="O2" value="3.9" spread="NA">Only one sample was collected for this measurement</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Concentration (Tmax)</title>
        <description>The amount of time needed for maximum drug concentration to be reached.</description>
        <time_frame>24 hour period following dose administration Day 1 to 2</time_frame>
        <population>Consisted of all subjects who had sufficient plasma concentration data to facilitate the calculation of the time to maximum plasma drug concentration as determined by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>NKTR-181</title>
            <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR</description>
          </group>
          <group group_id="O2">
            <title>Oxycodone IR 40 mg</title>
            <description>One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Concentration (Tmax)</title>
          <description>The amount of time needed for maximum drug concentration to be reached.</description>
          <population>Consisted of all subjects who had sufficient plasma concentration data to facilitate the calculation of the time to maximum plasma drug concentration as determined by the pharmacokineticist.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Plasma Drug Concentration at Hour 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1970" spread="477"/>
                    <measurement group_id="O2" value="35.7" spread="33.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2360" spread="1230"/>
                    <measurement group_id="O2" value="54.1" spread="13.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1350" spread="656"/>
                    <measurement group_id="O2" value="46.7" spread="15.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="388" spread="230"/>
                    <measurement group_id="O2" value="27.1" spread="7.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="185" spread="30.4"/>
                    <measurement group_id="O2" value="14.8" spread="NA">There is only one participant</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Drug Concentration at Hour 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.5" spread="13.7"/>
                    <measurement group_id="O2" value="3.9" spread="NA">There is only one participant</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time to Maximum Concentration (Tmax) measured in hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.54" spread="0.676"/>
                    <measurement group_id="O2" value="2.21" spread="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>Number of patients who experienced any type of adverse event as a result of one of the treatments.</description>
        <time_frame>19 days</time_frame>
        <population>Consisted of all subjects who received at least 1 dose of NKTR-181 or Oxycodone IR.</population>
        <group_list>
          <group group_id="O1">
            <title>NKTR-181</title>
            <description>NKTR-181 400 mg and placebo for oxycodone IR one tablet of each once</description>
          </group>
          <group group_id="O2">
            <title>Oxycodone IR 40 mg</title>
            <description>Oxycodone IR 40 mg and placebo for NKTR-181 one tablet of each once</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>Number of patients who experienced any type of adverse event as a result of one of the treatments.</description>
          <population>Consisted of all subjects who received at least 1 dose of NKTR-181 or Oxycodone IR.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>19 days post-dose of NKTR-181 or Oxycodone IR 40 mg</time_frame>
      <desc>All adverse events and their duration were listed. Adverse events that occurred on or after study dose administration were summarized. Verbatim terms were mapped to PTs and system organ classes (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA).</desc>
      <group_list>
        <group group_id="E1">
          <title>NKTR-181</title>
          <description>Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR</description>
        </group>
        <group group_id="E2">
          <title>Oxycodone IR 40 mg</title>
          <description>One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <description>One subject experienced insomnia that was treated with trazodone and resolved within 1-2 days. The insomnia was deemed not related to the study drug (NKTR-181)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <description>One subject experienced back pain that was treated with paracetamol and resolved within 1-2 days. The back pain was deemed not related to the study drug (NKTR-181).</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There are restrictions to the PI's rights to discuss or publish trial results.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was originally planned for 24 patients. However enrollment was stopped due to the CDP being stopped at 8 and therefore limits the generalizability of this data.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Nektar Therapeutics</organization>
      <phone>415-482-5416</phone>
      <email>medicalaffairs@nektar.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/NCT03802227
org study id: 18-181-26
nct id: NCT03802227
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to evaluate the effect of NKTR-181 on brain activity in
      healthy, non-physically dependent recreational opioid users. This study will last about 88
      days for each participant.
This study is a single-center study in which approximately 24 subjects will be randomized to
      one of two treatment groups. Subjects will enter a screening period between Day -28 and Day
      -2. Upon meeting all criteria for enrollment, on Day -1 subjects will enter the clinical
      research study unit (CRSU) for an overnight confinement. On Day 1, subjects will undergo a
      baseline MRI and will then be randomized to NKTR-181 or oxycodone immediate release (IR).
      Once randomized, subjects will receive a single dose of study drug (NKTR-181 or oxycodone IR)
      and matched alternate-treatment placebo. Subjects will undergo a series of three fMRIs
      (functional magnetic resonance imaging) post dose (at hours 1, 2, and 4). At post-dose hours
      0.5, 1, 2, 3, 4, 5, 6, and 8, pupillometry will be performed and PK blood samples will be
      drawn. Following a 14- to 17-day safety follow-up period, subjects will return to the
      research facility clinic for the End of Study (EOS) visit (Day 16-19).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A double-blind, double-dummy, parallel-group, randomized, positive control study.
primary purpose: Basic Science
masking: Triple (Participant, Care Provider, Investigator)
measure: Brain Activity Measured Via fMRI
time frame: 8 hour period following dose of NKTR-181
description: The primary objective of the study was to evaluate the effects of NKTR-181 on brain activity. Functional MRI assessments in subjects administered opioids such as morphine, buprenorphine, and nalbuphine have shown drug-induced signaling changes in reward structures such as the nucleus accumbens, orbitofrontal cortex, and hippocampus, as well as changes in the functional connectivity of reward circuitry (Becerra, 2006; Gear, 2013; Upadhyay, 2012).
measure: Change in Pupil Diameter Via Pupillometry
time frame: 24 hour period following dose administration Day 1 to 2
description: Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.
measure: Plasma Drug Concentration
time frame: 24 hour period following dose administration Day 1 to 2
description: Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.
measure: Time to Maximum Concentration (Tmax)
time frame: 24 hour period following dose administration Day 1 to 2
description: The amount of time needed for maximum drug concentration to be reached.
measure: Treatment-Emergent Adverse Events (TEAEs)
time frame: 19 days
description: Number of patients who experienced any type of adverse event as a result of one of the treatments.
arm group label: Group 1
arm group type: Experimental
description: NKTR-181 400 mg and oxycodone IR placebo
arm group label: Group 2
arm group type: Experimental
description: Oxycodone IR 40 mg and NKTR-181 placebo
intervention type: Drug
intervention name: NKTR-181
description: A combination of NKTR-181 and oxycodone IR placebo
arm group label: Group 1
intervention type: Drug
intervention name: Oxycodone IR
description: A combination of oxycodone IR and NKTR-181 placebo
arm group label: Group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Study Director
role: Study Director
affiliation: Nektar Therapeutics
facility: 
country: United States
responsible party type: Sponsor
mesh term: Chronic Pain
mesh term: Oxycodone
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was originally planned for 24 patients. However enrollment was stopped due to the CDP being stopped at 8 and therefore limits the generalizability of this data.
point of contact: 