<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/NCT03789318</url>
  </required_header>
  <id_info>
    <org_study_id>CA-PS-204</org_study_id>
    <nct_id>NCT03789318</nct_id>
  </id_info>
  <brief_title>Study in Subjects Undergoing Complete Abdominoplasty</brief_title>
  <official_title>A Phase 2, Randomized, Double-blind, Placebo-Controlled Efficacy, Pharmacokinetics and Safety Study of CA-008 in Subjects Undergoing Complete Abdominoplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Concentric Analgesics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Concentric Analgesics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 2, single center, randomized, double-blind, placebo-controlled, parallel design study&#xD;
      of CA-008 vs. placebo in subjects undergoing an elective C-ABD under general anesthesia&#xD;
      supplemented with a bupivacaine hydrochloride (HCl)transverse abdominis plane (TAP) block.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel&#xD;
      design study evaluating up to 4 ascending dose level cohorts, each evaluating a single dose&#xD;
      of CA-008 vs. placebo injected/instilled during an elective C-ABD. Up to 72 subjects may be&#xD;
      randomized in 4 cohorts.&#xD;
&#xD;
      For each subject, postsurgical assessments will be conducted in two parts:&#xD;
&#xD;
        -  Inpatient period: starts with completion of study treatment injection (T0) and continues&#xD;
           through 96 hours (T96h).&#xD;
&#xD;
        -  Outpatient period: begins on discharge from the inpatient unit through various follow up&#xD;
           visits to day 29 (D29)/week 4 (W4) after surgery. Note that additional follow up visits&#xD;
           may occur at any time or even after D29/W4 to follow adverse events (AEs) to resolution&#xD;
           or establishment of a new baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 3, 2018</start_date>
  <completion_date type="Actual">June 12, 2019</completion_date>
  <primary_completion_date type="Actual">May 16, 2019</primary_completion_date>
  <phase>Phase 2</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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain Intensity Scores at 96 Hours at Rest Using Numerical Rating Scale (NRS)</measure>
    <time_frame>96 hours</time_frame>
    <description>Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 96 hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores</measure>
    <time_frame>0 to 96 hours</time_frame>
    <description>Pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) from 0 to T96 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Opioid Cessation or Freedom</measure>
    <time_frame>From Surgery to Day 17</time_frame>
    <description>Time to the last use of opioid</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Opioid Free Subjects</measure>
    <time_frame>0 to 96 hours</time_frame>
    <description>Percent of subjects who were opioid free at 0-96 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Opioid Consumption</measure>
    <time_frame>0 to 96 hours</time_frame>
    <description>The sum of daily opioid consumption (in morphine equivalents)</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Postsurgical Pain</condition>
  <arm_group>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CA-008 5 mg</intervention_name>
    <description>5 mg CA-008 reconstituted in saline.</description>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <other_name>Vocacapsaicin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Each cohort will use placebo reconstituted in saline.</description>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine Hydrochloride</intervention_name>
    <description>0.25% administered pre-surgery</description>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydromorphone</intervention_name>
    <description>0.02 mg/kg IV administered intraoperatively</description>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <description>100 mcg IV administered intraoperatively</description>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <description>1000 mg IV administered intraoperatively</description>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone</intervention_name>
    <description>5-10 mg PO administered post-surgery</description>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <arm_group_label>CA-008 5 mg (0.05 mg/mL) Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohort 1</arm_group_label>
    <arm_group_label>Placebo for Cohorts 2 and 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CA-008 10 mg</intervention_name>
    <description>10 mg CA-008 reconstituted in saline.</description>
    <arm_group_label>CA-008 10 mg (0.1 mg/mL)</arm_group_label>
    <other_name>Vocacapsaicin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CA-008 15 mg</intervention_name>
    <description>15 mg CA-008 reconstituted in saline.</description>
    <arm_group_label>CA-008 15 mg (0.15 mg/mL)</arm_group_label>
    <other_name>Vocacapsaicin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Plan to undergo an elective complete abdominoplasty (C-ABD), without collateral&#xD;
             procedure or additional surgeries.&#xD;
&#xD;
          -  In the medical judgment of the investigator, be a reasonably healthy adult aged 18 -&#xD;
             65 years old, inclusive, and American Society of Anesthesiology (ASA) physical Class 1&#xD;
             or 2 at the time of randomization.&#xD;
&#xD;
          -  Unless the subject has a same sex partner, he or she must either be sterile&#xD;
             (surgically or biologically) or commit to an acceptable method of birth control while&#xD;
             participating in the study.&#xD;
&#xD;
          -  Have a body mass index ≤ 35 kg/m².&#xD;
&#xD;
          -  Be willing and able to sign the informed consent form (ICF) approved by an&#xD;
             Institutional Review Board (IRB).&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  In the opinion of the Investigator, have a concurrent painful condition that may&#xD;
             require analgesic treatment during the study period or may confound post-surgical pain&#xD;
             assessments.&#xD;
&#xD;
          -  Have a known allergy to chili peppers, capsaicin or the components of CA-008,&#xD;
             acetaminophen, bupivacaine, fentanyl hydromorphone or oxycodone.&#xD;
&#xD;
          -  As determined by the investigator have a history or clinical manifestation of&#xD;
             significant medical, neuropsychiatric or other condition, including a clinically&#xD;
             significant existing arrhythmia, left bundle branch block or abnormal ECG, myocardial&#xD;
             infarction or coronary arterial bypass graft surgery within the prior 12 months,&#xD;
             significant abnormal clinical laboratory test value, or known bleeding abnormality&#xD;
             that could preclude or impair study participation or interfere with study assessments.&#xD;
&#xD;
          -  The following are considered disallowed medications:&#xD;
&#xD;
               1. Be tolerant to opioids defined as those who have been receiving or have received&#xD;
                  chronic opioid therapy greater than 15 mg of oral morphine equivalents per day&#xD;
                  for greater than 3 out of 7 days per week over a one-month period within 6 months&#xD;
                  of screening.&#xD;
&#xD;
               2. Within 1 day prior to surgery and throughout the inpatient period, be taking any&#xD;
                  capsaicin-containing products, such as dietary supplements or over-the-counter&#xD;
                  (OTC) preparations, including topical formulations, and prescription medications.&#xD;
&#xD;
               3. Within the 7 days prior to surgery, be taking any central nervous system (CNS)&#xD;
                  active agent as an analgesic adjunct medication, such as anticonvulsants,&#xD;
                  antidepressants, benzodiazepines, sedative- hypnotics, clonidine and other&#xD;
                  central alpha-2 agents, ketamine or muscle relaxants.&#xD;
&#xD;
             i. These drugs are permitted if prescribed for non-pain indications and the dose has&#xD;
             been stable for at least 30 days prior to surgery.&#xD;
&#xD;
        ii. The use of benzodiazepines and the non-benzodiazepines are permitted to treat insomnia&#xD;
        during the postoperative period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alina Beaton, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lotus Clinical Research, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lotus Clinical Research, LLC</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>December 2, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <results_first_submitted>August 12, 2021</results_first_submitted>
  <results_first_submitted_qc>January 4, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">January 13, 2022</results_first_posted>
  <disposition_first_submitted>June 11, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>January 4, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 13, 2022</disposition_first_posted>
  <last_update_submitted>January 4, 2022</last_update_submitted>
  <last_update_submitted_qc>January 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Oxycodone</mesh_term>
    <mesh_term>Hydromorphone</mesh_term>
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>January 28, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03789318/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>April 24, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03789318/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
          <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="P2">
          <title>Placebo for Cohort 1</title>
          <description>Cohort 1: the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="P3">
          <title>CA-008 10 mg (0.1 mg/mL) Cohort 2</title>
          <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
        </group>
        <group group_id="P4">
          <title>CA-008 15 mg (0.15 mg/mL) Cohort 3</title>
          <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
        </group>
        <group group_id="P5">
          <title>Placebo for Cohorts 2 and 3</title>
          <description>Cohorts 2 &amp; 3: the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="12"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </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="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" 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="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
          <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="B2">
          <title>Placebo for Cohort 1</title>
          <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="B3">
          <title>CA-008 10 mg (0.1 mg/mL)</title>
          <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008</description>
        </group>
        <group group_id="B4">
          <title>CA-008 15 mg (0.15 mg/mL)</title>
          <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008</description>
        </group>
        <group group_id="B5">
          <title>Placebo for Cohorts 2 and 3</title>
          <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="12"/>
            <count group_id="B5" value="12"/>
            <count group_id="B6" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.8" spread="10.95"/>
                    <measurement group_id="B2" value="38.2" spread="7.17"/>
                    <measurement group_id="B3" value="43.3" spread="10.27"/>
                    <measurement group_id="B4" value="43.3" spread="6.74"/>
                    <measurement group_id="B5" value="38.3" spread="8.76"/>
                    <measurement group_id="B6" value="40.4" spread="8.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="3"/>
                  </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="1"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pain Intensity Scores at 96 Hours at Rest Using Numerical Rating Scale (NRS)</title>
        <description>Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 96 hours</description>
        <time_frame>96 hours</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
            <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O2">
            <title>Placebo for Cohort 1</title>
            <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O3">
            <title>CA-008 10 mg (0.1 mg/mL)</title>
            <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O4">
            <title>CA-008 15 mg (0.15 mg/mL)</title>
            <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O5">
            <title>Placebo for Cohorts 2 and 3</title>
            <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Intensity Scores at 96 Hours at Rest Using Numerical Rating Scale (NRS)</title>
          <description>Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 96 hours</description>
          <population>Safety population</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="2.59"/>
                    <measurement group_id="O2" value="2.0" spread="2.12"/>
                    <measurement group_id="O3" value="3.0" spread="2.22"/>
                    <measurement group_id="O4" value="2.8" spread="3.10"/>
                    <measurement group_id="O5" value="1.8" spread="1.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2912</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores</title>
        <description>Pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) from 0 to T96 hours</description>
        <time_frame>0 to 96 hours</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
            <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O2">
            <title>Placebo for Cohort 1</title>
            <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O3">
            <title>CA-008 10 mg (0.1 mg/mL)</title>
            <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O4">
            <title>CA-008 15 mg (0.15 mg/mL)</title>
            <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O5">
            <title>Placebo for Cohorts 2 and 3</title>
            <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores</title>
          <description>Pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) from 0 to T96 hours</description>
          <population>Safety population</population>
          <units>score on a scale*hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="392.98" spread="138.191"/>
                    <measurement group_id="O2" value="392.67" spread="163.025"/>
                    <measurement group_id="O3" value="384.94" spread="136.551"/>
                    <measurement group_id="O4" value="406.88" spread="220.821"/>
                    <measurement group_id="O5" value="356.23" spread="175.969"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4980</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Opioid Cessation or Freedom</title>
        <description>Time to the last use of opioid</description>
        <time_frame>From Surgery to Day 17</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
            <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O2">
            <title>Placebo for Cohort 1</title>
            <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O3">
            <title>CA-008 10 mg (0.1 mg/mL)</title>
            <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O4">
            <title>CA-008 15 mg (0.15 mg/mL)</title>
            <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O5">
            <title>Placebo for Cohorts 2 and 3</title>
            <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Opioid Cessation or Freedom</title>
          <description>Time to the last use of opioid</description>
          <population>Safety population</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.37" lower_limit="1.25" upper_limit="216.65"/>
                    <measurement group_id="O2" value="55.42" lower_limit="1.08" upper_limit="156.20"/>
                    <measurement group_id="O3" value="83.89" lower_limit="0.95" upper_limit="323.22"/>
                    <measurement group_id="O4" value="59.55" lower_limit="1.13" upper_limit="362.63"/>
                    <measurement group_id="O5" value="42.26" lower_limit="1.02" upper_limit="238.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1958</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Opioid Free Subjects</title>
        <description>Percent of subjects who were opioid free at 0-96 hours</description>
        <time_frame>0 to 96 hours</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
            <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O2">
            <title>Placebo for Cohort 1</title>
            <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O3">
            <title>CA-008 10 mg (0.1 mg/mL)</title>
            <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O4">
            <title>CA-008 15 mg (0.15 mg/mL)</title>
            <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O5">
            <title>Placebo for Cohorts 2 and 3</title>
            <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Opioid Free Subjects</title>
          <description>Percent of subjects who were opioid free at 0-96 hours</description>
          <population>Safety population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9546</p_value>
            <method>Regression, Logistic</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Opioid Consumption</title>
        <description>The sum of daily opioid consumption (in morphine equivalents)</description>
        <time_frame>0 to 96 hours</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
            <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O2">
            <title>Placebo for Cohort 1</title>
            <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
          <group group_id="O3">
            <title>CA-008 10 mg (0.1 mg/mL)</title>
            <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O4">
            <title>CA-008 15 mg (0.15 mg/mL)</title>
            <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
          </group>
          <group group_id="O5">
            <title>Placebo for Cohorts 2 and 3</title>
            <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Total Opioid Consumption</title>
          <description>The sum of daily opioid consumption (in morphine equivalents)</description>
          <population>Safety population</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="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.83" spread="52.246"/>
                    <measurement group_id="O2" value="96.67" spread="63.134"/>
                    <measurement group_id="O3" value="69.77" spread="41.710"/>
                    <measurement group_id="O4" value="58.00" spread="69.170"/>
                    <measurement group_id="O5" value="77.85" spread="72.524"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4434</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Approximately 76 days per subject from screening to the day 29 (D29) visit (however this could be longer to follow any AE to resolution or establishment of a new baseline)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CA-008 5 mg (0.05 mg/mL) Cohort 1</title>
          <description>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
CA-008 5 mg: 5 mg CA-008 reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="E2">
          <title>Placebo for Cohort 1</title>
          <description>Cohort 1:&#xD;
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
        <group group_id="E3">
          <title>CA-008 10 mg (0.1 mg/mL)</title>
          <description>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 10 mg: 10 mg CA-008 reconstituted in saline.</description>
        </group>
        <group group_id="E4">
          <title>CA-008 15 mg (0.15 mg/mL)</title>
          <description>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery&#xD;
CA-008 15 mg: 15 mg CA-008 reconstituted in saline.</description>
        </group>
        <group group_id="E5">
          <title>Placebo for Cohorts 2 and 3</title>
          <description>Cohorts 2 &amp; 3:&#xD;
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.&#xD;
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).&#xD;
Placebo: Each cohort will use placebo reconstituted in saline.&#xD;
Bupivacaine Hydrochloride: 0.25% administered pre-surgery&#xD;
Hydromorphone: 0.02 mg/kg IV administered intraoperatively&#xD;
Fentanyl: 100 mcg IV administered intraoperatively&#xD;
Acetaminophen: 1000 mg IV administered intraoperatively&#xD;
Oxycodone: 5-10 mg PO administered post-surgery</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Non-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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Abortion spontaneous</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lip oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Incision site cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Abdominal wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Airway complication of anaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Flap necrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Incision site pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Post procedural haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Seroma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Abortion spontaneous</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Respiratory tract congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus generalized</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Clinical Operations</name_or_title>
      <organization>Concentric Analgesics</organization>
      <phone>14154847921</phone>
      <email>nancy@concentricanalgesics.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/NCT03789318
org study id: CA-PS-204
nct id: NCT03789318
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase 2, single center, randomized, double-blind, placebo-controlled, parallel design study
      of CA-008 vs. placebo in subjects undergoing an elective C-ABD under general anesthesia
      supplemented with a bupivacaine hydrochloride (HCl)transverse abdominis plane (TAP) block.
This is a Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel
      design study evaluating up to 4 ascending dose level cohorts, each evaluating a single dose
      of CA-008 vs. placebo injected/instilled during an elective C-ABD. Up to 72 subjects may be
      randomized in 4 cohorts.

      For each subject, postsurgical assessments will be conducted in two parts:

        -  Inpatient period: starts with completion of study treatment injection (T0) and continues
           through 96 hours (T96h).

        -  Outpatient period: begins on discharge from the inpatient unit through various follow up
           visits to day 29 (D29)/week 4 (W4) after surgery. Note that additional follow up visits
           may occur at any time or even after D29/W4 to follow adverse events (AEs) to resolution
           or establishment of a new baseline.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Pain Intensity Scores at 96 Hours at Rest Using Numerical Rating Scale (NRS)
time frame: 96 hours
description: Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 96 hours
measure: Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores
time frame: 0 to 96 hours
description: Pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) from 0 to T96 hours
measure: Time to Opioid Cessation or Freedom
time frame: From Surgery to Day 17
description: Time to the last use of opioid
measure: Percent of Opioid Free Subjects
time frame: 0 to 96 hours
description: Percent of subjects who were opioid free at 0-96 hours
measure: Total Opioid Consumption
time frame: 0 to 96 hours
description: The sum of daily opioid consumption (in morphine equivalents)
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
arm group type: Active Comparator
description: Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).
arm group label: Placebo for Cohort 1
arm group type: Placebo Comparator
description: Cohort 1:
Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator.
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).
arm group label: CA-008 10 mg (0.1 mg/mL)
arm group type: Active Comparator
description: Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).
arm group label: CA-008 15 mg (0.15 mg/mL)
arm group type: Active Comparator
description: Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).
arm group label: Placebo for Cohorts 2 and 3
arm group type: Placebo Comparator
description: Cohorts 2 & 3:
Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator.
The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).
intervention type: Drug
intervention name: CA-008 5 mg
description: 5 mg CA-008 reconstituted in saline.
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
other name: Vocacapsaicin
intervention type: Drug
intervention name: Placebo
description: Each cohort will use placebo reconstituted in saline.
arm group label: Placebo for Cohort 1
arm group label: Placebo for Cohorts 2 and 3
intervention type: Drug
intervention name: Bupivacaine Hydrochloride
description: 0.25% administered pre-surgery
arm group label: CA-008 10 mg (0.1 mg/mL)
arm group label: CA-008 15 mg (0.15 mg/mL)
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
arm group label: Placebo for Cohort 1
arm group label: Placebo for Cohorts 2 and 3
intervention type: Drug
intervention name: Hydromorphone
description: 0.02 mg/kg IV administered intraoperatively
arm group label: CA-008 10 mg (0.1 mg/mL)
arm group label: CA-008 15 mg (0.15 mg/mL)
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
arm group label: Placebo for Cohort 1
arm group label: Placebo for Cohorts 2 and 3
intervention type: Drug
intervention name: Fentanyl
description: 100 mcg IV administered intraoperatively
arm group label: CA-008 10 mg (0.1 mg/mL)
arm group label: CA-008 15 mg (0.15 mg/mL)
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
arm group label: Placebo for Cohort 1
arm group label: Placebo for Cohorts 2 and 3
intervention type: Drug
intervention name: Acetaminophen
description: 1000 mg IV administered intraoperatively
arm group label: CA-008 10 mg (0.1 mg/mL)
arm group label: CA-008 15 mg (0.15 mg/mL)
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
arm group label: Placebo for Cohort 1
arm group label: Placebo for Cohorts 2 and 3
intervention type: Drug
intervention name: Oxycodone
description: 5-10 mg PO administered post-surgery
arm group label: CA-008 10 mg (0.1 mg/mL)
arm group label: CA-008 15 mg (0.15 mg/mL)
arm group label: CA-008 5 mg (0.05 mg/mL) Cohort 1
arm group label: Placebo for Cohort 1
arm group label: Placebo for Cohorts 2 and 3
intervention type: Drug
intervention name: CA-008 10 mg
description: 10 mg CA-008 reconstituted in saline.
arm group label: CA-008 10 mg (0.1 mg/mL)
other name: Vocacapsaicin
intervention type: Drug
intervention name: CA-008 15 mg
description: 15 mg CA-008 reconstituted in saline.
arm group label: CA-008 15 mg (0.15 mg/mL)
other name: Vocacapsaicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Alina Beaton, MD
role: Principal Investigator
affiliation: Lotus Clinical Research, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Acetaminophen
mesh term: Fentanyl
mesh term: Oxycodone
mesh term: Hydromorphone
mesh term: Bupivacaine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 