<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/NCT02255500</url>
  </required_header>
  <id_info>
    <org_study_id>402-C-406</org_study_id>
    <nct_id>NCT02255500</nct_id>
  </id_info>
  <brief_title>EXPAREL Infiltration in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Total Knee Arthroplasty</brief_title>
  <official_title>Evaluation of the Pharmacokinetics and Safety of Local Administration of EXPAREL in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Unilateral Total Knee Arthroplasty</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 EXPAREL in&#xD;
      subjects who undergo femoral nerve block with bupivacaine HCl for unilateral total knee&#xD;
      arthroplasty (TKA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      On Day 1, eligible subjects will receive a single 20 mL dose of bupivacaine hydrochloride&#xD;
      (HCl) 0.5% with epinephrine 1:200,000 within 2 hours prior to the surgical procedure as an&#xD;
      ultrasound-guided femoral nerve block (FNB). EXPAREL 266 mg expanded to 60 mL with&#xD;
      preservative-free sterile normal saline will be infiltrated into the surgical site prior to&#xD;
      wound closure. There will be no local coadministration of the two drugs.&#xD;
&#xD;
      Blood samples for bupivacaine pharmacokinetic (PK) analysis will be obtained from subjects at&#xD;
      baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes,&#xD;
      and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours after the beginning of EXPAREL administration,&#xD;
      and on Day 14.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 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>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
    <description>The maximum observed plasma concentration of a drug in the body after the drug has been administered.&#xD;
Blood samples for bupivacaine pharmacokinetic (PK) analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Peak Plasma Concentration (Tmax)</measure>
    <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
    <description>The time to reach the maximum observed plasma concentration (Cmax)&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)</measure>
    <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
    <description>Total drug exposure up to the last measurable concentration&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)</measure>
    <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
    <description>Total drug exposure, extrapolated to infinity&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Apparent Terminal Elimination Rate Constant (λz)</measure>
    <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
    <description>Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Apparent Terminal Elimination Half-life (t1/2el)</measure>
    <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
    <description>Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Bupivacaine FNB + EXPAREL Infiltration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Femoral nerve block with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine FNB</intervention_name>
    <description>A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.</description>
    <arm_group_label>Bupivacaine FNB + EXPAREL Infiltration</arm_group_label>
    <other_name>Bupivacaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EXPAREL Infiltration</intervention_name>
    <description>A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
    <arm_group_label>Bupivacaine FNB + EXPAREL Infiltration</arm_group_label>
    <other_name>Liposomal bupivacaine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females ≥18 years of age.&#xD;
&#xD;
          2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.&#xD;
&#xD;
          3. Scheduled to undergo femoral nerve block in conjunction with unilateral TKA.&#xD;
&#xD;
          4. Female subjects must be surgically sterile, at least 2 years postmenopausal, or using&#xD;
             a medically acceptable method of birth control. Females of childbearing potential must&#xD;
             have a documented negative blood or urine pregnancy test result within 24 hours before&#xD;
             surgery.&#xD;
&#xD;
          5. Able to provide informed consent, adhere to the study schedule, and complete all study&#xD;
             assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics&#xD;
             or opioids.&#xD;
&#xD;
          2. Contraindication to bupivacaine.&#xD;
&#xD;
          3. Received bupivacaine or any other local anesthetic within 7 days of EXPAREL&#xD;
             administration.&#xD;
&#xD;
          4. Currently pregnant, nursing, or planning to become pregnant during the study or within&#xD;
             1 month after EXPAREL administration.&#xD;
&#xD;
          5. Planned concurrent surgical procedure (e.g., bilateral TKA).&#xD;
&#xD;
          6. Body weight &lt;50 kg (110 pounds) or a body mass index ≥45 kg/m2.&#xD;
&#xD;
          7. Received any investigational drug within 30 days prior to EXPAREL administration,&#xD;
             and/or has planned administration of another investigational product or procedure&#xD;
             during the subject's participation in this study.&#xD;
&#xD;
          8. Previous participation in an EXPAREL study.&#xD;
&#xD;
          9. Malignancy in the last 2 years, with the exception of non-metastatic basal cell or&#xD;
             squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.&#xD;
&#xD;
         10. Current or historical evidence of any clinically significant disease or condition,&#xD;
             especially cardiovascular or neurological conditions that, in the opinion of the&#xD;
             Investigator, may increase the risk of surgery or complicate the subject's&#xD;
             postsurgical course.&#xD;
&#xD;
         11. Clinically significant medical or psychiatric disease that, in the opinion of the&#xD;
             Investigator, would constitute a contraindication to participation in the study, or&#xD;
             cause inability to comply with the study requirements.&#xD;
&#xD;
             In addition, the subject will be ineligible to receive EXPAREL if he or she meets the&#xD;
             following criteria during surgery:&#xD;
&#xD;
         12. Any clinically significant event or condition uncovered during the surgery (e.g.,&#xD;
             excessive bleeding, acute sepsis) that might render the subject medically unstable or&#xD;
             complicate the subject's postsurgical course.&#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>David Leiman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Concepts, GP, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Concepts, GP, LLC</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</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>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <results_first_submitted>May 20, 2016</results_first_submitted>
  <results_first_submitted_qc>October 30, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 24, 2020</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>
  <keyword>Total knee arthroplasty</keyword>
  <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>Bupivacaine FNB + EXPAREL Infiltration</title>
          <description>Femoral nerve block with bupivacaine hydrochloride (HCl) 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
        </group>
        <group group_id="P2">
          <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
          <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bupivacaine FNB + EXPAREL Infiltration</title>
          <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
        </group>
        <group group_id="B2">
          <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
          <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</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="16"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="23"/>
          </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="67.1" spread="8.61"/>
                    <measurement group_id="B2" value="59.7" spread="7.04"/>
                    <measurement group_id="B3" value="64.9" spread="8.7"/>
                  </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="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </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="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="20"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="21"/>
                  </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>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="16"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax)</title>
        <description>The maximum observed plasma concentration of a drug in the body after the drug has been administered.&#xD;
Blood samples for bupivacaine pharmacokinetic (PK) analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
        <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
        <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine FNB + EXPAREL Infiltration</title>
            <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
            <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax)</title>
          <description>The maximum observed plasma concentration of a drug in the body after the drug has been administered.&#xD;
Blood samples for bupivacaine pharmacokinetic (PK) analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
          <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</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="14"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="499" spread="148"/>
                    <measurement group_id="O2" value="775" spread="299"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Peak Plasma Concentration (Tmax)</title>
        <description>The time to reach the maximum observed plasma concentration (Cmax)&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
        <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
        <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine FNB + EXPAREL Infiltration</title>
            <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
            <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Peak Plasma Concentration (Tmax)</title>
          <description>The time to reach the maximum observed plasma concentration (Cmax)&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
          <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
          <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="14"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.675" lower_limit="0.183" upper_limit="78.0"/>
                    <measurement group_id="O2" value="47.450" lower_limit="0.183" upper_limit="72.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)</title>
        <description>Total drug exposure up to the last measurable concentration&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
        <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
        <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine FNB + EXPAREL Infiltration</title>
            <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
            <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)</title>
          <description>Total drug exposure up to the last measurable concentration&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
          <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
          <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="14"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28234" spread="10710"/>
                    <measurement group_id="O2" value="46600" spread="16489"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)</title>
        <description>Total drug exposure, extrapolated to infinity&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
        <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine FNB + EXPAREL Infiltration</title>
            <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
            <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)</title>
          <description>Total drug exposure, extrapolated to infinity&#xD;
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
          <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="6"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25134" spread="11506"/>
                    <measurement group_id="O2" value="38489" spread="NA"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Apparent Terminal Elimination Rate Constant (λz)</title>
        <description>Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
        <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
        <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine FNB + EXPAREL Infiltration</title>
            <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
            <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
          </group>
        </group_list>
        <measure>
          <title>The Apparent Terminal Elimination Rate Constant (λz)</title>
          <description>Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
          <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</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="6"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0290" spread="0.0089"/>
                    <measurement group_id="O2" value=".0315" spread="NA"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Apparent Terminal Elimination Half-life (t1/2el)</title>
        <description>Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
        <time_frame>Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose</time_frame>
        <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine FNB + EXPAREL Infiltration</title>
            <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
            <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from &quot;Bupivacaine FNB + EXPAREL Infiltration.&quot;</description>
          </group>
        </group_list>
        <measure>
          <title>The Apparent Terminal Elimination Half-life (t1/2el)</title>
          <description>Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration</description>
          <population>The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.</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="6"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.9" spread="8.02"/>
                    <measurement group_id="O2" value="22" spread="NA"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bupivacaine FNB + EXPAREL Infiltration</title>
          <description>FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.</description>
        </group>
        <group group_id="E2">
          <title>Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine</title>
          <description>Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.&#xD;
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.&#xD;
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 infiltrated into the surgical site just prior to wound closure.</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypercapnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </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/NCT02255500
org study id: 402-C-406
nct id: NCT02255500
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the safety and pharmacokinetics of EXPAREL in
      subjects who undergo femoral nerve block with bupivacaine HCl for unilateral total knee
      arthroplasty (TKA).
On Day 1, eligible subjects will receive a single 20 mL dose of bupivacaine hydrochloride
      (HCl) 0.5% with epinephrine 1:200,000 within 2 hours prior to the surgical procedure as an
      ultrasound-guided femoral nerve block (FNB). EXPAREL 266 mg expanded to 60 mL with
      preservative-free sterile normal saline will be infiltrated into the surgical site prior to
      wound closure. There will be no local coadministration of the two drugs.

      Blood samples for bupivacaine pharmacokinetic (PK) analysis will be obtained from subjects at
      baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes,
      and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours after the beginning of EXPAREL administration,
      and on Day 14.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax)
time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
description: The maximum observed plasma concentration of a drug in the body after the drug has been administered.
Blood samples for bupivacaine pharmacokinetic (PK) analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
measure: Time to Peak Plasma Concentration (Tmax)
time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
description: The time to reach the maximum observed plasma concentration (Cmax)
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)
time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
description: Total drug exposure up to the last measurable concentration
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)
time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
description: Total drug exposure, extrapolated to infinity
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
measure: The Apparent Terminal Elimination Rate Constant (λz)
time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
description: Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
measure: The Apparent Terminal Elimination Half-life (t1/2el)
time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
description: Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
arm group label: Bupivacaine FNB + EXPAREL Infiltration
arm group type: Experimental
description: Femoral nerve block with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
intervention type: Drug
intervention name: Bupivacaine FNB
description: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
arm group label: Bupivacaine FNB + EXPAREL Infiltration
other name: Bupivacaine
intervention type: Drug
intervention name: EXPAREL Infiltration
description: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
arm group label: Bupivacaine FNB + EXPAREL Infiltration
other name: Liposomal bupivacaine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Leiman, MD
role: Principal Investigator
affiliation: Research Concepts, GP, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Bupivacaine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 