<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/NCT02199574</url>
  </required_header>
  <id_info>
    <org_study_id>402-C-401</org_study_id>
    <nct_id>NCT02199574</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Evaluation of EXPAREL in Adults Undergoing Tonsillectomy</brief_title>
  <official_title>Pharmacokinetic Evaluation of EXPAREL in Adults Undergoing Tonsillectomy</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 characterize the pharmacokinetic (PK) profile of a single&#xD;
      dose of EXPAREL (133 mg/10 mL) administered intraoperatively per normal infiltration for&#xD;
      prolonged analgesia in 12 adult subjects undergoing tonsillectomy with or without removal of&#xD;
      the adenoids.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Blood samples for bupivacaine PK analysis will be obtained from subjects at baseline (within&#xD;
      30 minutes prior to EXPAREL infiltration), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24,&#xD;
      36, 48, and 72 hours after the beginning of EXPAREL infiltration, and on Day 7.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax)</measure>
    <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve (AUC(0-t))</measure>
    <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Half-life</measure>
    <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve (AUC(0-infinity))</measure>
    <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The Apparent Terminal Elimination Rate Constant (λz)</measure>
    <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>EXPAREL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single administration of EXPAREL 133 mg (10 mL).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EXPAREL</intervention_name>
    <description>133 mg EXPAREL in 10 mL.</description>
    <arm_group_label>EXPAREL</arm_group_label>
    <other_name>bupivacaine liposome injectable suspension</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, ≥18 years of age at the Screening Visit.&#xD;
&#xD;
          -  Subjects undergoing tonsillectomy with or without removal of the adenoids.&#xD;
&#xD;
          -  Able and willing to comply with all study visits and procedures.&#xD;
&#xD;
          -  Willing and capable of providing written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.&#xD;
&#xD;
          -  Received any investigational drug within 30 days prior to EXPAREL administration,&#xD;
             and/or has planned administration of another investigational product or procedure&#xD;
             while participating in this study.&#xD;
&#xD;
          -  Currently pregnant, nursing, or planning to become pregnant during the study or within&#xD;
             1 month after EXPAREL administration. Female subjects must be surgically sterile, at&#xD;
             least 2 years postmenopausal, or using an acceptable method of birth control. If of&#xD;
             childbearing potential, must have a documented negative pregnancy test within 24 hours&#xD;
             before EXPAREL administration.&#xD;
&#xD;
          -  Subjects with significant medical conditions or laboratory results that, in the&#xD;
             opinion of the Investigator, indicate an increased vulnerability to EXPAREL and/or&#xD;
             procedures, or cause inability to comply with the study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Harold Minkowitz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Herman Memorial Hospital, Houston TX</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Hermann - Memorial City Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Village Surgery Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <results_first_submitted>May 20, 2016</results_first_submitted>
  <results_first_submitted_qc>May 20, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 29, 2016</results_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 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>EXPAREL</title>
          <description>Single administration of EXPAREL 133 mg (10 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_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>11 participants received 133 mg/10 mL EXPAREL following protocol amendment subsequent to 1 participant receiving 266 mg/20 mL EXPAREL according to the original protocol.</population>
      <group_list>
        <group group_id="B1">
          <title>EXPAREL</title>
          <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL: Protocol was amended after a single subject received a dose of 266 mg EXPAREL to a dose level of 133 mg EXPAREL.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="35.6" spread="13.30"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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_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>From time of study drug administration through Day 7 postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>EXPAREL</title>
            <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL: 133 mg EXPAREL in 10 mL.</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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="254" spread="82.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Maximum Plasma Concentration (Tmax)</title>
        <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>EXPAREL</title>
            <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL: Protocol was amended after a single subject received a dose of 266 mg EXPAREL to a dose level of 133 mg EXPAREL.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma 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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.50" lower_limit="0.22" upper_limit="35.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve (AUC(0-t))</title>
        <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>EXPAREL</title>
            <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL: Protocol was amended after a single subject received a dose of 266 mg EXPAREL to a dose level of 133 mg EXPAREL.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve (AUC(0-t))</title>
          <units>hours*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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7150" spread="3189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Terminal Elimination Half-life</title>
        <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>EXPAREL</title>
            <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL: Protocol was amended after a single subject received a dose of 266 mg EXPAREL to a dose level of 133 mg EXPAREL.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Elimination Half-life</title>
          <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="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.34" spread="2.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve (AUC(0-infinity))</title>
        <time_frame>From time of study drug administration through Day 7 postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>EXPAREL</title>
            <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve (AUC(0-infinity))</title>
          <units>hours*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="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6379" spread="2825"/>
                  </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>From time of study drug administration through Day 7 postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>EXPAREL</title>
            <description>Single administration of EXPAREL 133 mg (10 mL).&#xD;
EXPAREL</description>
          </group>
        </group_list>
        <measure>
          <title>The Apparent Terminal Elimination Rate Constant (λz)</title>
          <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="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07779" spread="0.02222"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>EXPAREL</title>
          <description>Single administration of EXPAREL 133 mg (10 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"/>
              </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="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" 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/NCT02199574
org study id: 402-C-401
nct id: NCT02199574
lead sponsor: 
has dmc: No
The purpose of this study is to characterize the pharmacokinetic (PK) profile of a single
      dose of EXPAREL (133 mg/10 mL) administered intraoperatively per normal infiltration for
      prolonged analgesia in 12 adult subjects undergoing tonsillectomy with or without removal of
      the adenoids.
Blood samples for bupivacaine PK analysis will be obtained from subjects at baseline (within
      30 minutes prior to EXPAREL infiltration), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24,
      36, 48, and 72 hours after the beginning of EXPAREL infiltration, and on Day 7.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax)
time frame: From time of study drug administration through Day 7 postdose
measure: Time to Maximum Plasma Concentration (Tmax)
time frame: From time of study drug administration through Day 7 postdose
measure: Area Under the Plasma Concentration Versus Time Curve (AUC(0-t))
time frame: From time of study drug administration through Day 7 postdose
measure: Apparent Terminal Elimination Half-life
time frame: From time of study drug administration through Day 7 postdose
measure: Area Under the Plasma Concentration Versus Time Curve (AUC(0-infinity))
time frame: From time of study drug administration through Day 7 postdose
measure: The Apparent Terminal Elimination Rate Constant (λz)
time frame: From time of study drug administration through Day 7 postdose
arm group label: EXPAREL
arm group type: Experimental
description: Single administration of EXPAREL 133 mg (10 mL).
intervention type: Drug
intervention name: EXPAREL
description: 133 mg EXPAREL in 10 mL.
arm group label: EXPAREL
other name: bupivacaine liposome injectable suspension
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Harold Minkowitz, MD
role: Principal Investigator
affiliation: Herman Memorial Hospital, Houston TX
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Bupivacaine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 