<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/NCT03307837</url>
  </required_header>
  <id_info>
    <org_study_id>CA-PS-2017-101</org_study_id>
    <nct_id>NCT03307837</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study of Intraoperative Administration of CA-008 for the Correction of Hallux Valgus Deformity</brief_title>
  <official_title>A Phase 1/Single Ascending Dose (SAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of a Single Intraoperative Administration of CA-008 in Subjects Undergoing Correction of Hallux Valgus Deformity</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>
      This is a single-center, randomized, double-blind, placebo-controlled, single ascending dose,&#xD;
      sequential-group Phase 1 study. The study will be conducted utilizing a cohort design, with&#xD;
      sequential groups of 8 subjects. Within each dose cohort, 6 subjects will be randomized to&#xD;
      active, and 2 will be randomized to placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, randomized, double-blind, placebo-controlled, single ascending dose,&#xD;
      sequential-group Phase 1 study.&#xD;
&#xD;
      The study will be conducted utilizing a cohort design, with sequential groups of 8 subjects.&#xD;
      Within each dose cohort, 6 subjects will be randomized to active, and 2 will be randomized to&#xD;
      placebo. Placebo patients from each cohort were pooled for analysis. The initial cohort will&#xD;
      receive the lowest planned dose of CA-008, and sequential cohorts will receive escalating&#xD;
      doses of CA-008 in a fixed volume of administration. There will be at least a 6-day period&#xD;
      between cohorts, in order to ensure a minimum of 3 days to review safety data from the last&#xD;
      subject in a cohort and to allow the meeting of the Data Monitoring Committee (DMC) to review&#xD;
      the safety data from the entire cohort prior to a making decision for dose escalation. Dose&#xD;
      escalation rules will be protocol defined.&#xD;
&#xD;
      Subjects will be undergoing unilateral transpositional first metatarsal osteotomy for the&#xD;
      correction of hallux valgus deformity (bunionectomy). In accordance with standard of care,&#xD;
      subjects will receive regional anesthesia (MAYO block) with 0.5% bupivacaine. Prior to wound&#xD;
      closure, 10 mL of study drug will be injected into the soft tissues and periosteum of the&#xD;
      surgical site.&#xD;
&#xD;
      After the surgery, subjects will be monitored for 48 hours at the trial site. Safety and&#xD;
      efficacy evaluations will be performed as described herein. Subjects will be required to meet&#xD;
      certain pre-specified criteria prior to discharge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2017</start_date>
  <completion_date type="Actual">April 25, 2018</completion_date>
  <primary_completion_date type="Actual">March 20, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Surgical Site Assessment</measure>
    <time_frame>24 and 48 hours post infiltration</time_frame>
    <description>Assessment of skin reactions to determine if any change from 24 to 48 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurosensory Assessment</measure>
    <time_frame>48 hours post infiltration</time_frame>
    <description>Change in neurosensory assessments of the skin surrounding the incision.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>11-point (0-10) Numerical Pain Rating Scale (NPRS)</measure>
    <time_frame>time 0 to Day 15</time_frame>
    <description>Pain as assessed by a standard 11-point (0-10) NPRS (with 10 as the worse outcome) Area under the curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative Use of Analgesics</measure>
    <time_frame>Daily up through Day 15</time_frame>
    <description>Use of postoperative analgesic therapy/treatments&#xD;
Opioid consumption is recorded on the concomitant medication and/or the rescue medications pages and is calculated as the sum of the morphine milligram equivalents (MEQ) of all the medications recorded as taken during the period. For subjects who discontinued from the efficacy portion of the study, all medications are included regardless of whether they were taken before or after the discontinuation</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Hallux Valgus Deformity</condition>
  <arm_group>
    <arm_group_label>CA-008 Cohort 1 0.5 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intra-operative, local administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CA-008 Cohort 2 1 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intra-operative, local administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CA-008 Cohort 3 2 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intra-operative, local administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CA-008 Cohort 4 3 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intra-operative, local administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CA-008 Cohort 5 4.2 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intra-operative, local administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intra-operative, local administration of saline (equivalent volume in active comparator arm)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CA-008</intervention_name>
    <description>Local administration during surgery</description>
    <arm_group_label>CA-008 Cohort 1 0.5 mg</arm_group_label>
    <arm_group_label>CA-008 Cohort 2 1 mg</arm_group_label>
    <arm_group_label>CA-008 Cohort 3 2 mg</arm_group_label>
    <arm_group_label>CA-008 Cohort 4 3 mg</arm_group_label>
    <arm_group_label>CA-008 Cohort 5 4.2 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Local administration during surgery</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female aged 18 - 65 years old, inclusive.&#xD;
&#xD;
          2. Planning to undergo a primary unilateral first metatarsal bunionectomy repair, without&#xD;
             collateral procedures.&#xD;
&#xD;
          3. Be American Society of Anesthesiology (ASA) physical Class 1 or 2.&#xD;
&#xD;
          4. In good health and capable of undergoing a bunionectomy under regional anesthesia.&#xD;
&#xD;
          5. No additional planned surgeries other than a bunionectomy during the course of the&#xD;
             study.&#xD;
&#xD;
          6. Male subjects must be either sterile (surgically or biologically), or commit to an&#xD;
             acceptable method of birth control while participating in the study.&#xD;
&#xD;
          7. Female subjects are eligible only if all of the following apply:&#xD;
&#xD;
               1. Not pregnant (female subject of child bearing potential must have a negative&#xD;
                  serum pregnancy tests at screening and negative urine pregnancy test before&#xD;
                  surgery);&#xD;
&#xD;
               2. Not lactating;&#xD;
&#xD;
               3. Not planning to become pregnant during the study;&#xD;
&#xD;
               4. Be surgically sterile; or at least two years post-menopausal; or have a&#xD;
                  monogamous partner who is surgically sterile; or is practicing double-barrier&#xD;
                  contraception; or practicing abstinence (must agree to use double-barrier&#xD;
                  contraception in the event of sexual activity); or using an insertable,&#xD;
                  injectable, transdermal, or combination oral contraceptive approved by the FDA&#xD;
                  for greater than 2 months prior to screening visits and commits to the use of an&#xD;
                  acceptable form of birth control for the duration of the study and for 30 days&#xD;
                  from completion of the study.&#xD;
&#xD;
          8. Have a body mass index ≤ 35 kg/m2.&#xD;
&#xD;
          9. Willing and able to sign the informed consent form (ICF) approved by the Institutional&#xD;
             Review Board (IRB).&#xD;
&#xD;
         10. Willing and able to complete the study procedures and pain scales, and to communicate&#xD;
             meaningfully in English with study personnel.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with a history of hypertension, cardiovascular disease and a history of&#xD;
             cerebrovascular events.&#xD;
&#xD;
          2. Subjects with concurrent painful conditions that may require analgesic treatment&#xD;
             during the study period, or, in the opinion of the Investigator, may confound&#xD;
             post-operative pain assessments.&#xD;
&#xD;
          3. Have been receiving or have received chronic opioid therapy defined as greater than 15&#xD;
             morphine equivalents units per day for greater than 3 out of 7 days per week over a&#xD;
             one-month period within 12 months of study treatment initiation.&#xD;
&#xD;
          4. Have a known allergy or intolerance to the following medications or related&#xD;
             substances: capsaicin, chili peppers, propofol, bupivacaine, benzodiazepines,&#xD;
             midazolam, oxycodone, or ondansetron.&#xD;
&#xD;
          5. Have a clinically significant abnormal clinical laboratory test value according to the&#xD;
             judgment of the investigator.&#xD;
&#xD;
          6. Have, as determined by the investigator or the study's medical monitor, a history or&#xD;
             clinical manifestations of significant renal, hepatic, cardiovascular, metabolic,&#xD;
             neurologic, psychiatric, or other condition that would preclude participation in the&#xD;
             study.&#xD;
&#xD;
          7. Use concurrent therapy that could interfere with the evaluation of efficacy or safety,&#xD;
             such as any drugs which, in the investigator's opinion, may exert significant&#xD;
             analgesic properties or act synergistically with CA-008.&#xD;
&#xD;
          8. Use of disallowed pain medications within 2 days prior to Day 1 (NSAIDs, COX-2&#xD;
             inhibitors, tramadol, ketamine, clonidine, gabapentin, pregabalin, or cannabinoids).&#xD;
&#xD;
          9. Use of central nervous system (CNS) active drugs such as benzodiazepines, tricyclic&#xD;
             antidepressants, SNRIs, or SSRIs for pain within seven days prior to Day 1. These&#xD;
             drugs are permitted for non-pain indications if the dose has been stable for at least&#xD;
             30 days prior to Day 1 and is planned to remain stable throughout the study. The use&#xD;
             of lorazepam and other sleep medications, except those containing analgesic&#xD;
             properties, is permitted.&#xD;
&#xD;
         10. Have evidence of a clinically significant 12-lead ECG abnormality according to the&#xD;
             judgment of the investigator, including QTcF &gt;450 for men and &gt;470 for women.&#xD;
&#xD;
         11. Use of dietary supplements or over-the-counter (OTC) medications containing&#xD;
             significant amounts of capsaicin within 1 day prior to Day 1, and throughout the&#xD;
             hospitalization period.&#xD;
&#xD;
         12. Subjects with active cutaneous disease, or other disease, at the anticipated site of&#xD;
             surgery.&#xD;
&#xD;
         13. History of peripheral vascular disease, sickle cell disease, vascular grafts, or&#xD;
             vasospastic disorders.&#xD;
&#xD;
         14. Use of parenteral or oral corticosteroid(s) within 14 days prior to Day 1.&#xD;
&#xD;
         15. Known bleeding disorder or is taking agents affecting coagulation preoperatively. Deep&#xD;
             venous thrombosis (DVT) prophylaxis of the surgeon's choice is permitted&#xD;
             postoperatively.&#xD;
&#xD;
         16. A medical condition that in the investigator's opinion could adversely impact the&#xD;
             subject's participation or safety, conduct of the study, or interfere with the pain&#xD;
             assessments.&#xD;
&#xD;
         17. Diabetes mellitus.&#xD;
&#xD;
         18. Use of antihypertensive agent or diabetic regimen at a dose that has not been stable&#xD;
             for at least 30 days, or which is not expected to remain stable throughout the study.&#xD;
&#xD;
         19. Use of digoxin, warfarin (see exception below), lithium, theophylline preparations,&#xD;
             aminoglycosides, and all antiarrhythmics except beta-blockers, and use of&#xD;
             anticonvulsants except benzodiazepines within 7 days prior to Day 1 and throughout the&#xD;
             study. (Use of warfarin is allowed, at the investigator's discretion, for DVT&#xD;
             prophylaxis after the surgery).&#xD;
&#xD;
         20. History of illicit drug use, or prescription medicine or alcohol abuse (regularly&#xD;
             drinks &gt; 4 units of alcohol per day; 8 oz. beer, 3 oz. wine, 1 oz. spirits) within the&#xD;
             past 2 years, in the opinion of the Investigator.&#xD;
&#xD;
         21. Have positive results on the alcohol breath test indicative of alcohol abuse or urine&#xD;
             drug screen indicative of illicit drug use (unless results can be explained by a&#xD;
             current prescription or acceptable over-the-counter medication at screening as&#xD;
             determined by the investigator) at screening, and/or prior to surgery.&#xD;
&#xD;
         22. Stable medication regimen for at least 14 days prior to the scheduled bunionectomy&#xD;
             procedure, within 5 half-lives of the specific prior medication (or, if half-life is&#xD;
             not known, within 48 hours) before dosing with study medication.&#xD;
&#xD;
         23. Participated in another clinical trial or used an investigational product within 30&#xD;
             days or five half-lives (whichever is longer) prior to the planned bunionectomy&#xD;
             surgery, or is scheduled to receive an investigational product other than CA-008 while&#xD;
             participating in the study.&#xD;
&#xD;
         24. Previously participated in a clinical study with CA-008 or capsaicin.&#xD;
&#xD;
         25. Subjects with peripheral neuropathies which would potentially confound the planned&#xD;
             neurosensory testing.&#xD;
&#xD;
         26. Any past or current medical condition that in opinion of investigator, puts subject at&#xD;
             undue safety risk for surgical complications or for use of the investigational&#xD;
             product.&#xD;
&#xD;
         27. Subjects who donated blood or plasma within the 30 days prior to screening.&#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>John Donovan, MD</last_name>
    <role>Study Director</role>
    <affiliation>Concentric Analgesics</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>June 2021</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <results_first_submitted>April 28, 2020</results_first_submitted>
  <results_first_submitted_qc>June 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 30, 2021</results_first_posted>
  <last_update_submitted>June 10, 2021</last_update_submitted>
  <last_update_submitted_qc>June 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Unilateral Transpositional First Metatarsal Osteotomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hallux Valgus</mesh_term>
    <mesh_term>Bunion</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_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 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03307837/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>March 31, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03307837/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of the 40 enrolled participants, all 40 met inclusion criteria and were randomized to treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>CA-008 Cohort 1 0.5 mg</title>
          <description>Active (CA-008) to Placebo</description>
        </group>
        <group group_id="P2">
          <title>CA-008 Cohort 2 1 mg</title>
          <description>Active (CA-008) to Placebo</description>
        </group>
        <group group_id="P3">
          <title>CA-008 Cohort 3 2 mg</title>
          <description>Active (CA-008) to Placebo</description>
        </group>
        <group group_id="P4">
          <title>CA-008 Cohort 4 3 mg</title>
          <description>Active (CA-008) to Placebo</description>
        </group>
        <group group_id="P5">
          <title>CA-008 Cohort 5 4.2 mg</title>
          <description>Active (CA-008) to Placebo</description>
        </group>
        <group group_id="P6">
          <title>Placebo</title>
          <description>Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <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 group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CA-008 Cohort 1 0.5 mg</title>
          <description>CA-008: The active moiety of CA-008, capsaicin that has certain properties for treatment of post-operative pain.</description>
        </group>
        <group group_id="B2">
          <title>CA-008 Cohort 2 1 mg</title>
          <description>CA-008: The active moiety of CA-008, capsaicin that has certain properties for treatment of post-operative pain.</description>
        </group>
        <group group_id="B3">
          <title>CA-008 Cohort 3 2 mg</title>
          <description>CA-008: The active moiety of CA-008, capsaicin that has certain properties for treatment of post-operative pain.</description>
        </group>
        <group group_id="B4">
          <title>CA-008 Cohort 4 3 mg</title>
          <description>CA-008: The active moiety of CA-008, capsaicin that has certain properties for treatment of post-operative pain.</description>
        </group>
        <group group_id="B5">
          <title>CA-008 Cohort 5 4.2 mg</title>
          <description>CA-008: The active moiety of CA-008, capsaicin that has certain properties for treatment of post-operative pain.</description>
        </group>
        <group group_id="B6">
          <title>CA-008 Placebo</title>
          <description>CA-008 Placebo: Placebo product</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="10"/>
            <count group_id="B7" value="40"/>
          </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="34.5" spread="12.94"/>
                    <measurement group_id="B2" value="32.0" spread="6.78"/>
                    <measurement group_id="B3" value="40.3" spread="12.52"/>
                    <measurement group_id="B4" value="39.5" spread="12.94"/>
                    <measurement group_id="B5" value="34.3" spread="10.25"/>
                    <measurement group_id="B6" value="34.9" spread="7.82"/>
                    <measurement group_id="B7" value="35.8" spread="10.2"/>
                  </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="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="6"/>
                  </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="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="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="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Surgical Site Assessment</title>
        <description>Assessment of skin reactions to determine if any change from 24 to 48 hours.</description>
        <time_frame>24 and 48 hours post infiltration</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>CA-008 in 0.5 mg dose</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>CA-008 in 1 mg dose</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>CA-008 in 2 mg dose</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>CA-008 in 3 mg dose</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>CA-008 in 4.2 mg dose</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>Placebo administration</description>
          </group>
        </group_list>
        <measure>
          <title>Surgical Site Assessment</title>
          <description>Assessment of skin reactions to determine if any change from 24 to 48 hours.</description>
          <population>Safety Population</population>
          <units>Number of skin reactions</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="10"/>
              </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="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Neurosensory Assessment</title>
        <description>Change in neurosensory assessments of the skin surrounding the incision.</description>
        <time_frame>48 hours post infiltration</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>CA-008 in doses of 0.5 mg</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>CA-008 in doses of 1 mg</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>CA-008 in doses of 2 mg</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>CA-008 in doses of 3 mg</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>CA-008 in doses of 4.2 mg</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>Placebo administration</description>
          </group>
        </group_list>
        <measure>
          <title>Neurosensory Assessment</title>
          <description>Change in neurosensory assessments of the skin surrounding the incision.</description>
          <population>Safety population</population>
          <units>Number of neurosensory abnormalities</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="10"/>
              </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="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>11-point (0-10) Numerical Pain Rating Scale (NPRS)</title>
        <description>Pain as assessed by a standard 11-point (0-10) NPRS (with 10 as the worse outcome) Area under the curve (AUC)</description>
        <time_frame>time 0 to Day 15</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>CA-008 in 0.5 mg dose</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>CA-008 in 1 mg dose</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>CA-008 in 2 mg dose</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>CA-008 in 3 mg dose</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>CA-008 in 4.2 mg dose</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>Placebo administration</description>
          </group>
        </group_list>
        <measure>
          <title>11-point (0-10) Numerical Pain Rating Scale (NPRS)</title>
          <description>Pain as assessed by a standard 11-point (0-10) NPRS (with 10 as the worse outcome) Area under the curve (AUC)</description>
          <units>Scores 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="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUC 0-12 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.57" spread="10.26"/>
                    <measurement group_id="O2" value="14.25" spread="7.07"/>
                    <measurement group_id="O3" value="29.82" spread="24.55"/>
                    <measurement group_id="O4" value="32.47" spread="27.95"/>
                    <measurement group_id="O5" value="30.07" spread="31.66"/>
                    <measurement group_id="O6" value="41.77" spread="30.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC 12-24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.07" spread="35.69"/>
                    <measurement group_id="O2" value="56.70" spread="30.72"/>
                    <measurement group_id="O3" value="78.88" spread="11.89"/>
                    <measurement group_id="O4" value="57.28" spread="39.58"/>
                    <measurement group_id="O5" value="43.98" spread="23.47"/>
                    <measurement group_id="O6" value="79.46" spread="19.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC 24-72 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.57" spread="82.15"/>
                    <measurement group_id="O2" value="163.48" spread="108.59"/>
                    <measurement group_id="O3" value="169.35" spread="47.44"/>
                    <measurement group_id="O4" value="126.53" spread="102.53"/>
                    <measurement group_id="O5" value="101.62" spread="63.19"/>
                    <measurement group_id="O6" value="215.75" spread="93.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC 24-96 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="169.08" spread="132.37"/>
                    <measurement group_id="O2" value="267.47" spread="177.48"/>
                    <measurement group_id="O3" value="251.07" spread="94.99"/>
                    <measurement group_id="O4" value="200.33" spread="167.29"/>
                    <measurement group_id="O5" value="133.70" spread="84.38"/>
                    <measurement group_id="O6" value="348.49" spread="169.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC 24 hours - 1 week</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="294.12" spread="258.23"/>
                    <measurement group_id="O2" value="534.62" spread="423.60"/>
                    <measurement group_id="O3" value="512.52" spread="269.58"/>
                    <measurement group_id="O4" value="317.30" spread="264.28"/>
                    <measurement group_id="O5" value="212.07" spread="144.15"/>
                    <measurement group_id="O6" value="718.80" spread="422.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC 24 hours - 2 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="555.60" spread="583.64"/>
                    <measurement group_id="O2" value="1150.53" spread="1127.42"/>
                    <measurement group_id="O3" value="972.87" spread="816.65"/>
                    <measurement group_id="O4" value="561.00" spread="429.33"/>
                    <measurement group_id="O5" value="452.37" spread="379.82"/>
                    <measurement group_id="O6" value="1588.12" spread="1165.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postoperative Use of Analgesics</title>
        <description>Use of postoperative analgesic therapy/treatments&#xD;
Opioid consumption is recorded on the concomitant medication and/or the rescue medications pages and is calculated as the sum of the morphine milligram equivalents (MEQ) of all the medications recorded as taken during the period. For subjects who discontinued from the efficacy portion of the study, all medications are included regardless of whether they were taken before or after the discontinuation</description>
        <time_frame>Daily up through Day 15</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>CA-008 in doses of 0.5 mg</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>CA-008 in doses of 1 mg</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3</title>
            <description>CA-008 in doses of 2 mg</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4</title>
            <description>CA-008 in doses of 3 mg</description>
          </group>
          <group group_id="O5">
            <title>Cohort 5</title>
            <description>CA-008 in doses of 4.2 mg</description>
          </group>
          <group group_id="O6">
            <title>Placebo</title>
            <description>Placebo administration</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Use of Analgesics</title>
          <description>Use of postoperative analgesic therapy/treatments&#xD;
Opioid consumption is recorded on the concomitant medication and/or the rescue medications pages and is calculated as the sum of the morphine milligram equivalents (MEQ) of all the medications recorded as taken during the period. For subjects who discontinued from the efficacy portion of the study, all medications are included regardless of whether they were taken before or after the discontinuation</description>
          <units>Morphine milligram equivalents (MEQ)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.00" spread="39.02"/>
                    <measurement group_id="O2" value="38.17" spread="39.78"/>
                    <measurement group_id="O3" value="68.75" spread="79.86"/>
                    <measurement group_id="O4" value="42.50" spread="41.53"/>
                    <measurement group_id="O5" value="47.50" spread="47.59"/>
                    <measurement group_id="O6" value="94.60" spread="58.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected up to 64 days for participants in the study. This was comprised of a screening period that could be up to 28 days and subsequent clinic visits through Day 29. A Day 36 visit was required only if the wound was not considered healed by Day 29.</time_frame>
      <desc>The definition of adverse event and/or serious adverse event, used to collect adverse event information in this study did not differ from the clinicaltrials.gov definitions.</desc>
      <group_list>
        <group group_id="E1">
          <title>CA-008 Cohort 1</title>
          <description>CA-008 in 0.5 mg</description>
        </group>
        <group group_id="E2">
          <title>CA-008 Cohort 2</title>
          <description>CA-008 in 1 mg</description>
        </group>
        <group group_id="E3">
          <title>CA-008 Cohort 3</title>
          <description>CA-008 in 2 mg</description>
        </group>
        <group group_id="E4">
          <title>CA-008 Cohort 4</title>
          <description>CA-008 in 3 mg</description>
        </group>
        <group group_id="E5">
          <title>CA-008 Cohort 5</title>
          <description>CA-008 in 4.2 mg</description>
        </group>
        <group group_id="E6">
          <title>Placebo</title>
          <description>Placebo administration</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2.5</frequency_threshold>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Muscle Strain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Wound complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </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" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. John Donovan, President and Founder</name_or_title>
      <organization>Concentric Analgesics</organization>
      <phone>415-676-8940</phone>
      <email>JOHN@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/NCT03307837
org study id: CA-PS-2017-101
nct id: NCT03307837
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single-center, randomized, double-blind, placebo-controlled, single ascending dose,
      sequential-group Phase 1 study. The study will be conducted utilizing a cohort design, with
      sequential groups of 8 subjects. Within each dose cohort, 6 subjects will be randomized to
      active, and 2 will be randomized to placebo.
This is a single-center, randomized, double-blind, placebo-controlled, single ascending dose,
      sequential-group Phase 1 study.

      The study will be conducted utilizing a cohort design, with sequential groups of 8 subjects.
      Within each dose cohort, 6 subjects will be randomized to active, and 2 will be randomized to
      placebo. Placebo patients from each cohort were pooled for analysis. The initial cohort will
      receive the lowest planned dose of CA-008, and sequential cohorts will receive escalating
      doses of CA-008 in a fixed volume of administration. There will be at least a 6-day period
      between cohorts, in order to ensure a minimum of 3 days to review safety data from the last
      subject in a cohort and to allow the meeting of the Data Monitoring Committee (DMC) to review
      the safety data from the entire cohort prior to a making decision for dose escalation. Dose
      escalation rules will be protocol defined.

      Subjects will be undergoing unilateral transpositional first metatarsal osteotomy for the
      correction of hallux valgus deformity (bunionectomy). In accordance with standard of care,
      subjects will receive regional anesthesia (MAYO block) with 0.5% bupivacaine. Prior to wound
      closure, 10 mL of study drug will be injected into the soft tissues and periosteum of the
      surgical site.

      After the surgery, subjects will be monitored for 48 hours at the trial site. Safety and
      efficacy evaluations will be performed as described herein. Subjects will be required to meet
      certain pre-specified criteria prior to discharge.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Surgical Site Assessment
time frame: 24 and 48 hours post infiltration
description: Assessment of skin reactions to determine if any change from 24 to 48 hours.
measure: Neurosensory Assessment
time frame: 48 hours post infiltration
description: Change in neurosensory assessments of the skin surrounding the incision.
measure: 11-point (0-10) Numerical Pain Rating Scale (NPRS)
time frame: time 0 to Day 15
description: Pain as assessed by a standard 11-point (0-10) NPRS (with 10 as the worse outcome) Area under the curve (AUC)
measure: Postoperative Use of Analgesics
time frame: Daily up through Day 15
description: Use of postoperative analgesic therapy/treatments
Opioid consumption is recorded on the concomitant medication and/or the rescue medications pages and is calculated as the sum of the morphine milligram equivalents (MEQ) of all the medications recorded as taken during the period. For subjects who discontinued from the efficacy portion of the study, all medications are included regardless of whether they were taken before or after the discontinuation
arm group label: CA-008 Cohort 1 0.5 mg
arm group type: Active Comparator
description: Intra-operative, local administration
arm group label: CA-008 Cohort 2 1 mg
arm group type: Active Comparator
description: Intra-operative, local administration
arm group label: CA-008 Cohort 3 2 mg
arm group type: Active Comparator
description: Intra-operative, local administration
arm group label: CA-008 Cohort 4 3 mg
arm group type: Active Comparator
description: Intra-operative, local administration
arm group label: CA-008 Cohort 5 4.2 mg
arm group type: Active Comparator
description: Intra-operative, local administration
arm group label: Placebo
arm group type: Placebo Comparator
description: Intra-operative, local administration of saline (equivalent volume in active comparator arm)
intervention type: Drug
intervention name: CA-008
description: Local administration during surgery
arm group label: CA-008 Cohort 1 0.5 mg
arm group label: CA-008 Cohort 2 1 mg
arm group label: CA-008 Cohort 3 2 mg
arm group label: CA-008 Cohort 4 3 mg
arm group label: CA-008 Cohort 5 4.2 mg
intervention type: Drug
intervention name: Placebo
description: Local administration during surgery
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: John Donovan, MD
role: Study Director
affiliation: Concentric Analgesics
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hallux Valgus
mesh term: Bunion
mesh term: Congenital Abnormalities
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 