<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/NCT01683071</url>
  </required_header>
  <id_info>
    <org_study_id>402-C-323</org_study_id>
    <nct_id>NCT01683071</nct_id>
  </id_info>
  <brief_title>Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia Following Total Knee Arthroplasty</brief_title>
  <official_title>A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Single Injection Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia in Subjects Undergoing 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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objectives of Part 1 are to (1) evaluate three dose levels of liposome&#xD;
      bupivacaine versus placebo with respect to the magnitude and duration of the analgesic effect&#xD;
      achieved following single dose injection femoral nerve block with liposome bupivacaine, and&#xD;
      (2) select a single therapeutic dose of liposome bupivacaine from the three dose levels to be&#xD;
      tested in Part 2.&#xD;
&#xD;
      Part 2: The primary objective of Part 2 is to compare the magnitude and duration of the&#xD;
      analgesic effect of single injection femoral nerve block of a single dose level of liposome&#xD;
      bupivacaine (selected from Part 1) with placebo (preservative-free normal saline).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2/3, multicenter, randomized, double-blind, parallel-group,&#xD;
      placebo-controlled, dose-ranging study in subjects undergoing primary unilateral total knee&#xD;
      arthroplasty (TKA) under general or spinal anesthesia. Note: Bupivacaine cannot be used as&#xD;
      the spinal anesthetic.&#xD;
&#xD;
      Part 1 During Part 1 of the study, approximately 100 subjects (25 per treatment arm) will be&#xD;
      randomized to receive a single dose injection femoral nerve block with either one of three&#xD;
      doses of liposome bupivacaine (67, 133, or 266 mg) or placebo in 20 mL under ultrasound&#xD;
      guidance. Preservative-free normal saline will be added to the 67 mg and 133 mg doses of&#xD;
      study drug to achieve a volume of 20 mL.&#xD;
&#xD;
      Part 2 In Part 2 of the study, approximately 180 subjects (randomized 1:1, resulting in&#xD;
      approximately 90 liposome bupivacaine subjects and 90 placebo subjects) will receive a single&#xD;
      dose injection femoral nerve block with the selected dose level of liposome bupivacaine&#xD;
      (i.e., 67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours</measure>
    <time_frame>0-72 hours</time_frame>
    <description>AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Postsurgical Opioid Consumption Through 72 Hours</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Total postsurgical opioid consumption of opioid rescue pain medication (converted to IV morphine equivalents) through 72 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Opioid Rescue Through 72 Hours</measure>
    <time_frame>0-72 hours</time_frame>
    <description>Time to first opioid rescue medication consumed through 72 hours</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">297</enrollment>
  <condition>Postoperative Pain</condition>
  <arm_group>
    <arm_group_label>(Part 1) EXPAREL 67 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Part 1) EXPAREL 133 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Part 1) EXPAREL 266 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Part 1) Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Part 2) EXPAREL 266 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Part 2) Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Normal saline 20 mL as single-injection femoral nerve block prior to total knee arthroplasty</description>
    <arm_group_label>(Part 1) Placebo</arm_group_label>
    <arm_group_label>(Part 2) Placebo</arm_group_label>
    <other_name>Preservative-free normal saline.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EXPAREL 67 mg</intervention_name>
    <description>5 mL EXPAREL expanded with 15 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty</description>
    <arm_group_label>(Part 1) EXPAREL 67 mg</arm_group_label>
    <other_name>Bupivacaine liposome injectable suspension 67 mg/5 mL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EXPAREL 133 mg</intervention_name>
    <description>10 mL EXPAREL expanded with 10 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty</description>
    <arm_group_label>(Part 1) EXPAREL 133 mg</arm_group_label>
    <other_name>Bupivacaine liposome injectable suspension 133 mg/10 mL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EXPAREL 266 mg</intervention_name>
    <description>20 mL EXPAREL as single-injection femoral nerve block prior to total knee arthroplasty</description>
    <arm_group_label>(Part 1) EXPAREL 266 mg</arm_group_label>
    <arm_group_label>(Part 2) EXPAREL 266 mg</arm_group_label>
    <other_name>Bupivacaine liposome injectable suspension 266 mg/20 mL</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, &gt;=18 years of age.&#xD;
&#xD;
          2. Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.&#xD;
&#xD;
          3. American Society of Anesthesiologists (ASA) Physical Status 1, 2, or 3.&#xD;
&#xD;
          4. Able to demonstrate motor function by performing a 20-meter walk, unassisted with the&#xD;
             optional use of a 4-legged walker, and sensory function by exhibiting sensitivity to&#xD;
             cold.&#xD;
&#xD;
          5. Able to provide informed consent, adhere to the study visit schedule, and complete all&#xD;
             study assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently pregnant, nursing, or planning to become pregnant during the study or within&#xD;
             1 month after study drug administration. Female subjects must be surgically sterile,&#xD;
             at least 2 years menopausal, or using an acceptable method of birth control.&#xD;
&#xD;
             If of childbearing potential, must have a documented negative pregnancy test within 24&#xD;
             hours before surgery.&#xD;
&#xD;
          2. Planned concurrent surgical procedure (e.g., bilateral TKA).&#xD;
&#xD;
          3. Use of any of the following medications within the times specified before surgery:&#xD;
&#xD;
             long-acting opioid medication, NSAIDs, aspirin (except for low-dose aspirin used for&#xD;
             cardioprotection) or acetaminophen within 3 days, or and any opioid medication within&#xD;
             24 hours.&#xD;
&#xD;
          4. Concurrent painful physical condition or concurrent surgery that may require analgesic&#xD;
             treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not&#xD;
             strictly related to the surgical site administered study treatment, and which may&#xD;
             confound the postsurgical assessments (e.g., significant pain from other joints&#xD;
             including the non-index knee joint, chronic neuropathic pain, prior contralateral TKA,&#xD;
             concurrent foot surgery).&#xD;
&#xD;
          5. Initiation of treatment with any of the following medications within 1 month of study&#xD;
             drug administration or if the medication(s) are being given to control pain: selective&#xD;
             serotonin reuptake inhibitors (SSRIs), selective norepinepherine reuptake inhibitors&#xD;
             (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®).&#xD;
&#xD;
          6. Current use of systemic glucocorticosteroids within 1 month of enrollment in this&#xD;
             study.&#xD;
&#xD;
          7. Body weight &lt; 50 kilograms (110 pounds) or a body mass index ≥ 40 kg/m2.&#xD;
&#xD;
          8. Contraindication to hydromorphone, oxycodone, or bupivacaine.&#xD;
&#xD;
          9. Administration of an investigational drug within 30 days or 5 elimination half-lives&#xD;
             of such investigational drug, whichever is longer, prior to study drug administration,&#xD;
             or planned administration of another investigational product or procedure during the&#xD;
             subject's participation in this study.&#xD;
&#xD;
         10. Previous participation in a liposome bupivacaine study.&#xD;
&#xD;
         11. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription&#xD;
             medicine(s), or alcohol within the past 2 years.&#xD;
&#xD;
         12. Failure to pass the urine drug screen.&#xD;
&#xD;
         13. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the&#xD;
             opinion of the Investigator, could interfere with study assessments or compliance.&#xD;
&#xD;
         14. 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;
         15. 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;
         16. Significant medical conditions or laboratory results that, in the opinion of the&#xD;
             Investigator, indicate an increased vulnerability to study drugs and procedures.&#xD;
&#xD;
         17. Subjects who are planned to receive Entereg® (alvimopan).&#xD;
&#xD;
         18. Subjects who will receive prophylactic antiemetics or planned postsurgical antiemetics&#xD;
             given without regard to the subject's emesis needs.&#xD;
&#xD;
         19. Use of dexmedetomidine HCl (Precedex®) within 3 days of surgery.&#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>Erol Onel, MD</last_name>
    <role>Study Director</role>
    <affiliation>Pacira Pharmaceuticals, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ACHIEVE CLINICAL RESEARCH LLC 2017 Canyon Road Suite 41</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HORIZON RESEARCH GROUP INC 3610 Springhill Memorial Dr. N</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veritas Research, LLC</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SHOALS MEDICAL TRIALS INC. 1300 S Montgomery Ave</name>
      <address>
        <city>Sheffield</city>
        <state>Alabama</state>
        <zip>35660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PHOENIX ORTHOPAEDIC SURGEONS 2525 W. Greenway Road Suite 114</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ALLIANCE RESEARCH CENTERS 24411 Health Center Drive Suite 350</name>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ORTHOPADIC SURGERY Loma Linda University Health Care Dept. Pf Orthopaedic Surgery 250 East Caroline Street Suite A</name>
      <address>
        <city>San Bernardino</city>
        <state>California</state>
        <zip>92508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ilfeld, Brian (Thornton) UNIVERSITY OF CALIFORNIA, SAN DIEGO 10610 Hunters Glen Drive</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FLORIDA RESEARCH ASSOCIATES, LLC / FLORIDA ORTHOPAEDIC ASSOCIATES 740 W. Plymouth Ave</name>
      <address>
        <city>DeLand</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JACKSON MEMORIAL HOSPITAL UNVERSITY OF MIAMI 1611 Nw. 12th Ave C300</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PENSACOLA RESEARCH CONSULTANTS,INC 5149 N.9th Avenue Suite 241</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SHERIDAN CLINICAL RESEARCH, INC. 1613 N. Harrison Parkway Building C Suite 200</name>
      <address>
        <city>Sunrise</city>
        <state>Florida</state>
        <zip>33323</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PHOENIX CLINICAL RESEARCH,LLC 7171 N. University Drive Suite 100</name>
      <address>
        <city>Tamarac</city>
        <state>Florida</state>
        <zip>33321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNIVERSITY OF KANSAS HOSPITAL &amp; MEDICAL CENTER Dept. Of Anesthesiology 3901 Rainbow Blvd. Ms 1034</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BEAUMONT HEALTH SYSTEM 44201 Dequindre Road Suite Pob 120</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>COOPER UNIVERSITY HOSPITAL 1 Cooper Plaza 202 Dorrance Building</name>
      <address>
        <city>Camden</city>
        <state>New Jersey</state>
        <zip>08103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNIVERSITY OF MEDICINE AND DENSITRY OF NEW JERSEY/NEW JERSEY MEDICAL SCHOOL 185 South Orange Ave. Department of Anesthesiology - MSB E538</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NORTHERN WESTCHESTER HOSPTIAL Department Of Clinical Trials 400 East Main St.</name>
      <address>
        <city>Mount Kisco</city>
        <state>New York</state>
        <zip>10549</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ST. LUKE-ROOSEVELT HOSPITAL CENTER Dept. Of Anesthesiology 1111 Amsterdam Ave. Travis Bld. 7</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INSALL-SCOTT-KELLY INSTITUTE 210 East 64th Street</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Department Of Anesthesiology 101 Manning Drive N0021, Cb 7010</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CLEVELAND CLINIC FAIRVIEW HOSPTIAL 1801 Lorain Avenue</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CLEVELAND CLINIC 9500 Euclid Ave P-77</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PENN STATE MILTON S. HERSHEY MEDICAL CENTER H187,500 University Drive</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>THOMAS JEFFERSON UNIVERSITY Dept. Of Anesthesiology 111 S. 11th Street Suite G 8490</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC PRESBYTERIAN SHADYSIDE/ DEPT. OF ANESTHESIOLOGY POSNER PAIN CENTER 532 South Aiken Avenue Suite 407</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNIVERSITY OF TEXAS MEDICAL BRANCH Dept. Chairman, Orthopedic Surgery &amp; Rehabilitation 2.316 Rebecca Sealy Hospital 301 University Blvd.</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77551</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RESEARCH CONCEPTS,GP LLC 921 Gessner Rd. Anesthesia Dept., Classroom F</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRISTUS ST. JOHN HOSPITAL 18300 St. John Dr., 2nd Floor, Surgery</name>
      <address>
        <city>Nassau Bay</city>
        <state>Texas</state>
        <zip>77058</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <results_first_submitted>September 29, 2020</results_first_submitted>
  <results_first_submitted_qc>November 15, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 9, 2020</results_first_posted>
  <disposition_first_submitted>March 24, 2014</disposition_first_submitted>
  <disposition_first_submitted_qc>March 24, 2014</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">April 21, 2014</disposition_first_posted>
  <last_update_submitted>November 15, 2020</last_update_submitted>
  <last_update_submitted_qc>November 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Total knee arthroplasty</keyword>
  <keyword>Analgesia</keyword>
  <keyword>Pain management</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 19, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT01683071/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 9, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT01683071/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited between September 24, 2012 and December 20, 2013 at 23 sites in the US</recruitment_details>
      <pre_assignment_details>An unblinded dose selection committee reviewed Part 1 results for the primary endpoint, total postsurgical opioid consumption, time to first opioid rescue, and safety data, and recommended a dose level and sample size for Part 2.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>(Part 1) EXPAREL 67 mg</title>
          <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="P2">
          <title>(Part 1) EXPAREL 133 mg</title>
          <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="P3">
          <title>(Part 1) EXPAREL 266 mg</title>
          <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="P4">
          <title>(Part 1) Placebo</title>
          <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="P5">
          <title>(Part 2) EXPAREL 266 mg</title>
          <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="P6">
          <title>(Part 2) Placebo</title>
          <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="25"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="22"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Surgery Cancelled</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <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 group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive study drug</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Early termination; met exclusion criteria</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</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="99"/>
                <participants group_id="P6" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>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="82"/>
                <participants group_id="P6" count="82"/>
              </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="17"/>
                <participants group_id="P6" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</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="3"/>
                <participants group_id="P6" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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="2"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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="3"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Surgery cancelled</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="4"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive study drug</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="2"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Met exclusion criterion</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="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</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="1"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by investigator decision</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="1"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety population included all participants who received study drug, with analysis by actual treatment received.</population>
      <group_list>
        <group group_id="B1">
          <title>(Part 1) EXPAREL 67 mg</title>
          <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="B2">
          <title>(Part 1) EXPAREL 133 mg</title>
          <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="B3">
          <title>(Part 1) EXPAREL 266 mg</title>
          <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="B4">
          <title>(Part 1) Placebo</title>
          <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="B5">
          <title>(Part 2) EXPAREL 266 mg</title>
          <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="B6">
          <title>(Part 2) Placebo</title>
          <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="B7">
          <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="22"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="24"/>
            <count group_id="B4" value="24"/>
            <count group_id="B5" value="92"/>
            <count group_id="B6" value="92"/>
            <count group_id="B7" value="278"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="92"/>
                    <count group_id="B7" value="278"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.5" spread="8.41"/>
                    <measurement group_id="B2" value="65.7" spread="7.30"/>
                    <measurement group_id="B3" value="66.4" spread="8.94"/>
                    <measurement group_id="B4" value="66.1" spread="12.17"/>
                    <measurement group_id="B5" value="66.4" spread="10.35"/>
                    <measurement group_id="B6" value="63.6" spread="8.76"/>
                    <measurement group_id="B7" value="65.0" spread="9.67"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="92"/>
                    <count group_id="B7" value="278"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="52"/>
                    <measurement group_id="B6" value="57"/>
                    <measurement group_id="B7" value="161"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="40"/>
                    <measurement group_id="B6" value="35"/>
                    <measurement group_id="B7" value="117"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="92"/>
                    <count group_id="B7" value="278"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="9"/>
                    <measurement group_id="B7" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="84"/>
                    <measurement group_id="B6" value="83"/>
                    <measurement group_id="B7" value="254"/>
                  </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 group_id="B7" 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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="92"/>
                    <count group_id="B7" value="278"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="4"/>
                  </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 group_id="B7" 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="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="15"/>
                    <measurement group_id="B6" value="14"/>
                    <measurement group_id="B7" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="75"/>
                    <measurement group_id="B6" value="76"/>
                    <measurement group_id="B7" value="234"/>
                  </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="1"/>
                    <measurement group_id="B7" value="1"/>
                  </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 group_id="B7" 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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="92"/>
                    <count group_id="B7" value="278"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="92"/>
                    <measurement group_id="B6" value="92"/>
                    <measurement group_id="B7" value="278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>American Society of Anesthesiologists (ASA) classification</title>
          <description>ASA classification: 1=normal healthy patient; 2=patient with mild systemic disease; 3=patient with severe systemic disease; 4=patient with severe systemic disease that is a constant threat to life; 5=a moribund patient who is not expected to survive without the operation; 6=a declared brain-dead patient whose organs are being removed for donor purposes.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="92"/>
                    <count group_id="B7" value="278"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="38"/>
                    <measurement group_id="B6" value="49"/>
                    <measurement group_id="B7" value="142"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="47"/>
                    <measurement group_id="B6" value="40"/>
                    <measurement group_id="B7" value="125"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;/= 4</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 group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Anesthesia</title>
          <population>One participant in the Part 2 placebo group did not have type of anesthesia recorded and therefore was not included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="91"/>
                    <count group_id="B7" value="277"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>General</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="62"/>
                    <measurement group_id="B6" value="56"/>
                    <measurement group_id="B7" value="183"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Spinal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="28"/>
                    <measurement group_id="B6" value="35"/>
                    <measurement group_id="B7" value="91"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of Surgery</title>
          <population>One participant in the Part 2 placebo group did not have duration of surgery recorded and therefore was not included in this analysis.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="92"/>
                    <count group_id="B6" value="91"/>
                    <count group_id="B7" value="277"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85.8" spread="25.53"/>
                    <measurement group_id="B2" value="88.5" spread="27.96"/>
                    <measurement group_id="B3" value="96.0" spread="37.94"/>
                    <measurement group_id="B4" value="85.0" spread="35.53"/>
                    <measurement group_id="B5" value="94.1" spread="34.43"/>
                    <measurement group_id="B6" value="94.9" spread="37.54"/>
                    <measurement group_id="B7" value="94.5" spread="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Incision length</title>
          <population>One participant in the Part 1 EXPAREL 266 mg group, one participant in the Part 2 EXPAREL 266 mg group, and three participants in the Part 2 placebo group did not have incision length recorded and therefore were not included in this analysis.</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="22"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="23"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="91"/>
                    <count group_id="B6" value="89"/>
                    <count group_id="B7" value="273"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.51" spread="2.457"/>
                    <measurement group_id="B2" value="14.98" spread="3.650"/>
                    <measurement group_id="B3" value="15.23" spread="2.834"/>
                    <measurement group_id="B4" value="18.25" spread="3.870"/>
                    <measurement group_id="B5" value="16.92" spread="4.987"/>
                    <measurement group_id="B6" value="16.29" spread="5.189"/>
                    <measurement group_id="B7" value="16.6" spread="5.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours</title>
        <description>AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)</description>
        <time_frame>0-72 hours</time_frame>
        <population>Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received)</population>
        <group_list>
          <group group_id="O1">
            <title>(Part 1) EXPAREL 67 mg</title>
            <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively&#xD;
EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg</description>
          </group>
          <group group_id="O2">
            <title>(Part 1) EXPAREL 133 mg</title>
            <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively&#xD;
EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg</description>
          </group>
          <group group_id="O3">
            <title>(Part 1) EXPAREL 266 mg</title>
            <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively&#xD;
EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg</description>
          </group>
          <group group_id="O4">
            <title>(Part 1) Placebo</title>
            <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively&#xD;
Placebo: Normal saline 20 mL</description>
          </group>
          <group group_id="O5">
            <title>(Part 2) EXPAREL 266 mg</title>
            <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively&#xD;
EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg</description>
          </group>
          <group group_id="O6">
            <title>(Part 2) Placebo</title>
            <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively&#xD;
Placebo: Normal saline 20 mL</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours</title>
          <description>AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)</description>
          <population>Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received)</population>
          <units>score on a scale * hr</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="92"/>
                <count group_id="O6" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="533.4" spread="33.15"/>
                    <measurement group_id="O2" value="427.2" spread="31.73"/>
                    <measurement group_id="O3" value="436.2" spread="31.79"/>
                    <measurement group_id="O4" value="530.5" spread="31.73"/>
                    <measurement group_id="O5" value="418.9" spread="16.86"/>
                    <measurement group_id="O6" value="515.5" spread="16.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9494</p_value>
            <method>ANCOVA</method>
            <param_type>LSMD</param_type>
            <param_value>2.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-88</ci_lower_limit>
            <ci_upper_limit>94</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0237</p_value>
            <method>ANCOVA</method>
            <param_type>LSMD</param_type>
            <param_value>-103.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-192</ci_lower_limit>
            <ci_upper_limit>-14</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0386</p_value>
            <method>ANCOVA</method>
            <param_type>LSMD</param_type>
            <param_value>-94.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-184</ci_lower_limit>
            <ci_upper_limit>-5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <param_type>LSMD</param_type>
            <param_value>-96.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-144</ci_lower_limit>
            <ci_upper_limit>-49</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Postsurgical Opioid Consumption Through 72 Hours</title>
        <description>Total postsurgical opioid consumption of opioid rescue pain medication (converted to IV morphine equivalents) through 72 hours</description>
        <time_frame>0-72 hours</time_frame>
        <population>Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received)</population>
        <group_list>
          <group group_id="O1">
            <title>(Part 1) EXPAREL 67 mg</title>
            <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O2">
            <title>(Part 1) EXPAREL 133 mg</title>
            <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O3">
            <title>(Part 1) EXPAREL 266 mg</title>
            <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O4">
            <title>(Part 1) Placebo</title>
            <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O5">
            <title>(Part 2) EXPAREL 266 mg</title>
            <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O6">
            <title>(Part 2) Placebo</title>
            <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
        </group_list>
        <measure>
          <title>Total Postsurgical Opioid Consumption Through 72 Hours</title>
          <description>Total postsurgical opioid consumption of opioid rescue pain medication (converted to IV morphine equivalents) through 72 hours</description>
          <population>Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received)</population>
          <units>mg morphine equivalents</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="92"/>
                <count group_id="O6" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.69" spread="75.972"/>
                    <measurement group_id="O2" value="100.35" spread="53.177"/>
                    <measurement group_id="O3" value="105.96" spread="53.402"/>
                    <measurement group_id="O4" value="124.78" spread="58.743"/>
                    <measurement group_id="O5" value="93.19" spread="58.133"/>
                    <measurement group_id="O6" value="122.08" spread="70.312"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6182</p_value>
            <method>ANOVA</method>
            <param_type>Geometric LSM ratio</param_type>
            <param_value>0.90</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1097</p_value>
            <method>ANOVA</method>
            <param_type>Geometric LSM ratio</param_type>
            <param_value>0.73</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>1.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4046</p_value>
            <method>ANOVA</method>
            <param_type>Geometric LSM ratio</param_type>
            <param_value>0.85</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0016</p_value>
            <method>ANOVA</method>
            <param_type>Geometric LSM ratio</param_type>
            <param_value>0.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Opioid Rescue Through 72 Hours</title>
        <description>Time to first opioid rescue medication consumed through 72 hours</description>
        <time_frame>0-72 hours</time_frame>
        <population>Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received)</population>
        <group_list>
          <group group_id="O1">
            <title>(Part 1) EXPAREL 67 mg</title>
            <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O2">
            <title>(Part 1) EXPAREL 133 mg</title>
            <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O3">
            <title>(Part 1) EXPAREL 266 mg</title>
            <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O4">
            <title>(Part 1) Placebo</title>
            <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O5">
            <title>(Part 2) EXPAREL 266 mg</title>
            <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
          <group group_id="O6">
            <title>(Part 2) Placebo</title>
            <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Opioid Rescue Through 72 Hours</title>
          <description>Time to first opioid rescue medication consumed through 72 hours</description>
          <population>Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received)</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="92"/>
                <count group_id="O6" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49" lower_limit="0.300" upper_limit="0.650"/>
                    <measurement group_id="O2" value="0.37" lower_limit="0.283" upper_limit="0.700"/>
                    <measurement group_id="O3" value="1.29" lower_limit="0.367" upper_limit="2.350"/>
                    <measurement group_id="O4" value="0.41" lower_limit="0.300" upper_limit="0.550"/>
                    <measurement group_id="O5" value="0.44" lower_limit="0.400" upper_limit="0.533"/>
                    <measurement group_id="O6" value="0.43" lower_limit="0.367" upper_limit="0.567"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From screening through postsurgical day 30</time_frame>
      <desc>An AE was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality.&#xD;
Serious AEs were defined as per clinicaltrials.gov.&#xD;
The safety analysis set includes all subjects who received study drug, based on treatment received.</desc>
      <group_list>
        <group group_id="E1">
          <title>(Part 1) EXPAREL 67 mg</title>
          <description>5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="E2">
          <title>(Part 1) EXPAREL 133 mg</title>
          <description>10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="E3">
          <title>(Part 1) EXPAREL 266 mg</title>
          <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="E4">
          <title>(Part 1) Placebo</title>
          <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="E5">
          <title>(Part 2) EXPAREL 266 mg</title>
          <description>20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
        <group group_id="E6">
          <title>(Part 2) Placebo</title>
          <description>20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 14.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac Failure Congestive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Local Swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Systemic Inflammatory Response Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Type IV Hypersensitivity Reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Device Related Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Wound Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wound Dehiscence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Wound Decomposition</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Wound Necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Hypovolemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Prerenal Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Pulmonary Congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Orthostatic Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 14.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="82" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="83" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="49" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="61" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="32" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="32" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="26" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="38" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="28" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="24" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Feeling Cold</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="8" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Local Swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Wound Dehiscence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Anemia Postoperative</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Body Temperature Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Mobility Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="15" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="19" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="11" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="12" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="33" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="31" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Pruritis Generalized</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="11" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E6" subjects_affected="8" subjects_at_risk="92"/>
              </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>Results conducted at Site shall not be published before 1st multicenter publication by Sponsor but can proceed if there is no such publication ≤18 months after study completion/termination at all sites and all data have been received. Before submitting manuscript/materials to an outside person/entity, site shall give Sponsor 60 days to review and comment. Site shall, upon request, further delay publication/presentation for ≤120 days to allow Sponsor to protect its interests in Inventions.</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/NCT01683071
org study id: 402-C-323
nct id: NCT01683071
lead sponsor: 
has dmc: Yes
The primary objectives of Part 1 are to (1) evaluate three dose levels of liposome
      bupivacaine versus placebo with respect to the magnitude and duration of the analgesic effect
      achieved following single dose injection femoral nerve block with liposome bupivacaine, and
      (2) select a single therapeutic dose of liposome bupivacaine from the three dose levels to be
      tested in Part 2.

      Part 2: The primary objective of Part 2 is to compare the magnitude and duration of the
      analgesic effect of single injection femoral nerve block of a single dose level of liposome
      bupivacaine (selected from Part 1) with placebo (preservative-free normal saline).
This is a Phase 2/3, multicenter, randomized, double-blind, parallel-group,
      placebo-controlled, dose-ranging study in subjects undergoing primary unilateral total knee
      arthroplasty (TKA) under general or spinal anesthesia. Note: Bupivacaine cannot be used as
      the spinal anesthetic.

      Part 1 During Part 1 of the study, approximately 100 subjects (25 per treatment arm) will be
      randomized to receive a single dose injection femoral nerve block with either one of three
      doses of liposome bupivacaine (67, 133, or 266 mg) or placebo in 20 mL under ultrasound
      guidance. Preservative-free normal saline will be added to the 67 mg and 133 mg doses of
      study drug to achieve a volume of 20 mL.

      Part 2 In Part 2 of the study, approximately 180 subjects (randomized 1:1, resulting in
      approximately 90 liposome bupivacaine subjects and 90 placebo subjects) will receive a single
      dose injection femoral nerve block with the selected dose level of liposome bupivacaine
      (i.e., 67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours
time frame: 0-72 hours
description: AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)
measure: Total Postsurgical Opioid Consumption Through 72 Hours
time frame: 0-72 hours
description: Total postsurgical opioid consumption of opioid rescue pain medication (converted to IV morphine equivalents) through 72 hours
measure: Time to First Opioid Rescue Through 72 Hours
time frame: 0-72 hours
description: Time to first opioid rescue medication consumed through 72 hours
arm group label: (Part 1) EXPAREL 67 mg
arm group type: Experimental
description: 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively
arm group label: (Part 1) EXPAREL 133 mg
arm group type: Experimental
description: 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively
arm group label: (Part 1) EXPAREL 266 mg
arm group type: Experimental
description: 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively
arm group label: (Part 1) Placebo
arm group type: Placebo Comparator
description: 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively
arm group label: (Part 2) EXPAREL 266 mg
arm group type: Experimental
description: 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively
arm group label: (Part 2) Placebo
arm group type: Placebo Comparator
description: 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively
intervention type: Drug
intervention name: Placebo
description: Normal saline 20 mL as single-injection femoral nerve block prior to total knee arthroplasty
arm group label: (Part 1) Placebo
arm group label: (Part 2) Placebo
other name: Preservative-free normal saline.
intervention type: Drug
intervention name: EXPAREL 67 mg
description: 5 mL EXPAREL expanded with 15 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty
arm group label: (Part 1) EXPAREL 67 mg
other name: Bupivacaine liposome injectable suspension 67 mg/5 mL
intervention type: Drug
intervention name: EXPAREL 133 mg
description: 10 mL EXPAREL expanded with 10 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty
arm group label: (Part 1) EXPAREL 133 mg
other name: Bupivacaine liposome injectable suspension 133 mg/10 mL
intervention type: Drug
intervention name: EXPAREL 266 mg
description: 20 mL EXPAREL as single-injection femoral nerve block prior to total knee arthroplasty
arm group label: (Part 1) EXPAREL 266 mg
arm group label: (Part 2) EXPAREL 266 mg
other name: Bupivacaine liposome injectable suspension 266 mg/20 mL
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Erol Onel, MD
role: Study Director
affiliation: Pacira Pharmaceuticals, Inc
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country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Bupivacaine
provided document: 
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certain agreements: 
point of contact: 