<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/NCT02210247</url>
  </required_header>
  <id_info>
    <org_study_id>402-C-113</org_study_id>
    <nct_id>NCT02210247</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers</brief_title>
  <official_title>An Open-Label Cohort Study to Evaluate the Safety and Pharmacokinetics of Redosing EXPAREL Via Local Subcutaneous Infiltration in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pacira Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pacira Pharmaceuticals, Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and pharmacokinetics of redosing EXPAREL&#xD;
      via local subcutaneous infiltration in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During Dosing Period 1, blood samples for pharmacokinetic (PK) analysis will be obtained&#xD;
      predose (15 minutes prior to administration of EXPAREL) through 12 hours postdose (i.e., at&#xD;
      15 and 30 minutes, 1, 2, 4, 8, and 12 hours) for Cohort 4; through 36 hours postdose (i.e.,&#xD;
      at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, and 36 hours) for Cohort 3; through 60 hours&#xD;
      postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, and 60 hours) for Cohort 2;&#xD;
      and through 72 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60,&#xD;
      and 72 hours) for Cohorts 1 and 5.&#xD;
&#xD;
      During Dosing Period 2 (Cohorts 2, 3, and 4 only), blood samples for PK analysis will be&#xD;
      obtained predose (15 minutes prior to administration of EXPAREL) through 72 hours postdose&#xD;
      (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Concentration (Tmax)</measure>
    <time_frame>Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)]</measure>
    <time_frame>Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Half-life</measure>
    <time_frame>Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The Apparent Terminal Elimination Rate Constant (λz)</measure>
    <time_frame>Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EXPAREL</intervention_name>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_label>Cohort 5</arm_group_label>
    <other_name>bupivacaine liposome injectable suspension</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or females ≥18 years of age.&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) physical status 1 or 2.&#xD;
&#xD;
          -  Female subjects must be surgically sterile, at least 2 years postmenopausal, or using&#xD;
             a medically acceptable method of birth control. If of childbearing potential, must&#xD;
             have a documented negative pregnancy test within 24 hours before the first study drug&#xD;
             administration.&#xD;
&#xD;
          -  Able to provide informed consent, adhere to the study visit schedule, and complete all&#xD;
             study assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity or idiosyncratic reactions to amide-type local&#xD;
             anesthetics.&#xD;
&#xD;
          -  History of abnormal bleeding tendencies/clotting disorders.&#xD;
&#xD;
          -  Regular use of anticoagulants (except for low dose aspirin for cardioprotection).&#xD;
&#xD;
          -  Received any investigational drug within 30 days prior to study drug administration,&#xD;
             and/or has planned administration of another investigational product or procedure&#xD;
             during his/her participation in this study.&#xD;
&#xD;
          -  Currently pregnant, nursing, or planning to become pregnant during the study or within&#xD;
             1 month after study drug administration.&#xD;
&#xD;
          -  Subjects with significant medical conditions or laboratory results that, in the&#xD;
             opinion of the Investigator, would constitute a contraindication to participation in&#xD;
             the study, or cause inability to comply with the study requirements.&#xD;
&#xD;
          -  Received bupivacaine or other local anesthetic within 7 days of first study drug&#xD;
             administration.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lukasz Biernat, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medpace Clinical Pharmacology Unit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medpace Clinical Pharmacology Unit</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</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>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <results_first_submitted>May 20, 2016</results_first_submitted>
  <results_first_submitted_qc>June 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 2, 2021</results_first_posted>
  <last_update_submitted>July 1, 2021</last_update_submitted>
  <last_update_submitted_qc>July 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1</title>
          <description>Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.&#xD;
EXPAREL</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2</title>
          <description>Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="P3">
          <title>Cohort 3</title>
          <description>Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="P4">
          <title>Cohort 4</title>
          <description>Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="P5">
          <title>Cohort 5</title>
          <description>Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1</title>
          <description>Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.&#xD;
EXPAREL</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2</title>
          <description>Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="B3">
          <title>Cohort 3</title>
          <description>Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="B4">
          <title>Cohort 4</title>
          <description>Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="B5">
          <title>Cohort 5</title>
          <description>Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
        </group>
        <group group_id="B6">
          <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="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="12"/>
            <count group_id="B5" value="12"/>
            <count group_id="B6" value="60"/>
          </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="45.6" spread="11.90"/>
                    <measurement group_id="B2" value="37.8" spread="11.66"/>
                    <measurement group_id="B3" value="36.9" spread="10.83"/>
                    <measurement group_id="B4" value="41.6" spread="12.38"/>
                    <measurement group_id="B5" value="44.1" spread="14.56"/>
                    <measurement group_id="B6" value="41.2" spread="12.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax)</title>
        <time_frame>Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax)</title>
          <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="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="129" spread="47"/>
                    <measurement group_id="O2" value="207" spread="57"/>
                    <measurement group_id="O3" value="202" spread="74"/>
                    <measurement group_id="O4" value="290" spread="119"/>
                    <measurement group_id="O5" value="246" spread="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Maximum Concentration (Tmax)</title>
        <time_frame>Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Concentration (Tmax)</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24" lower_limit="24" upper_limit="72"/>
                    <measurement group_id="O2" value="48" lower_limit="24" upper_limit="72"/>
                    <measurement group_id="O3" value="48" lower_limit="1" upper_limit="72"/>
                    <measurement group_id="O4" value="36" lower_limit="24" upper_limit="72"/>
                    <measurement group_id="O5" value="24" lower_limit="8" upper_limit="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)]</title>
        <time_frame>Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)]</title>
          <units>H*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="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5917" spread="1738"/>
                    <measurement group_id="O2" value="10976" spread="2879"/>
                    <measurement group_id="O3" value="10201" spread="3721"/>
                    <measurement group_id="O4" value="15227" spread="7463"/>
                    <measurement group_id="O5" value="11567" spread="3737"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Terminal Elimination Half-life</title>
        <time_frame>Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
        <population>Where n per group &lt;12, values were either not calculated or not reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Elimination Half-life</title>
          <population>Where n per group &lt;12, values were either not calculated or not reported.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.24" spread="22.64"/>
                    <measurement group_id="O2" value="44.88" spread="25.64"/>
                    <measurement group_id="O3" value="51.70" spread="26.99"/>
                    <measurement group_id="O4" value="33.22" spread="3.80"/>
                    <measurement group_id="O5" value="59.13" spread="25.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Apparent Terminal Elimination Rate Constant (λz)</title>
        <time_frame>Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects</time_frame>
        <population>Where n per group &lt;12, values were either not calculated or not reported.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>The Apparent Terminal Elimination Rate Constant (λz)</title>
          <population>Where n per group &lt;12, values were either not calculated or not reported.</population>
          <units>1/hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.009" spread="0.003"/>
                    <measurement group_id="O2" value="0.019" spread="0.007"/>
                    <measurement group_id="O3" value="0.016" spread="0.007"/>
                    <measurement group_id="O4" value="0.021" spread="0.002"/>
                    <measurement group_id="O5" value="0.014" spread="0.006"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1</title>
          <description>Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.&#xD;
EXPAREL</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2</title>
          <description>Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="E3">
          <title>Cohort 3</title>
          <description>Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="E4">
          <title>Cohort 4</title>
          <description>Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.&#xD;
EXPAREL</description>
        </group>
        <group group_id="E5">
          <title>Cohort 5</title>
          <description>Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).&#xD;
EXPAREL</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection-site reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vessel puncture site haematoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pacira Medical Information</name_or_title>
      <organization>Pacira Pharmaceuticals Inc.</organization>
      <phone>1-855-793-9727</phone>
      <email>MedInfo@pacira.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/NCT02210247
org study id: 402-C-113
nct id: NCT02210247
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the safety and pharmacokinetics of redosing EXPAREL
      via local subcutaneous infiltration in healthy volunteers.
During Dosing Period 1, blood samples for pharmacokinetic (PK) analysis will be obtained
      predose (15 minutes prior to administration of EXPAREL) through 12 hours postdose (i.e., at
      15 and 30 minutes, 1, 2, 4, 8, and 12 hours) for Cohort 4; through 36 hours postdose (i.e.,
      at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, and 36 hours) for Cohort 3; through 60 hours
      postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, and 60 hours) for Cohort 2;
      and through 72 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60,
      and 72 hours) for Cohorts 1 and 5.

      During Dosing Period 2 (Cohorts 2, 3, and 4 only), blood samples for PK analysis will be
      obtained predose (15 minutes prior to administration of EXPAREL) through 72 hours postdose
      (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax)
time frame: Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects
measure: Time to Maximum Concentration (Tmax)
time frame: Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects
measure: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)]
time frame: Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects
measure: Apparent Terminal Elimination Half-life
time frame: Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects
measure: The Apparent Terminal Elimination Rate Constant (λz)
time frame: Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects
arm group label: Cohort 1
arm group type: Active Comparator
description: Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.
arm group label: Cohort 2
arm group type: Active Comparator
description: Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
arm group label: Cohort 3
arm group type: Active Comparator
description: Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
arm group label: Cohort 4
arm group type: Active Comparator
description: Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
arm group label: Cohort 5
arm group type: Active Comparator
description: Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
intervention type: Drug
intervention name: EXPAREL
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
arm group label: Cohort 5
other name: bupivacaine liposome injectable suspension
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Lukasz Biernat, MD
role: Principal Investigator
affiliation: Medpace Clinical Pharmacology Unit
facility: 
country: United States
responsible party type: Sponsor
mesh term: Bupivacaine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 